New possibilities of stereotactic treatment of temporal lobe epilepsy (TLE).
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Amygdala↗
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Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.
OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66 years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.
Humans↗
[Effects of unilateral temporal lobectomy on verbal dichotic listening test].
Verbal dichotic listening test was conducted before and after anterior temporal lobectomy on 25 patients who underwent the operation because of their medication-resistant epileptic seizures. Their speech dominance by Wada test was all left sided. 1. Preoperatively, patients having the epileptogenic focus in the right temporal lobe (R-TLE) and those having the focus in the left (L-TLE) were, as expected, all right-ear dominant. The mean number of correct responses was fewer in L-TLE than in R-TLE group. 2. Postoperatively, no detrimental effects for recognition of verbal auditory stimuli by the ear contralateral to the focus was observed both in L-TLE and in R-TLE group. 3. Postoperatively, the ear-dominance shifted: to the left in patients with L-TLE, and to the right more conspicuously in patients with R-TLE compared to the preoperative scores. In other words, the recognition ability by the ears ipsilateral to the side of focus, or of resected temporal lobe, was ameliorated. Summarizing, the unilateral anterior temporal lobectomy did not cause "lesion effect" but yielded improvement of verbal auditory recognition by ears ipsilateral to the epileptogenic focus. Diminished epileptic bombardment resulted in by the resection surgery may be a possible explanation.
Adult↗
Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.
BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.
Humans↗
Morphological changes in the dentate gyrus in human temporal lobe epilepsy.
Multiple morphological and neurochemical changes are found in the dentate gyrus of humans with temporal lobe epilepsy (TLE). Three basically different types of changes will be discussed and some interrelationships considered. Neuronal loss in several regions of the hippocampal formation in human TLE has been recognized for many years, but only recently have the polymorph or hilar neurons been evaluated as a distinct group of neurons, and cell loss in this region is now being documented in many cases with severe TLE. Reorganization of afferents within the molecular layer of the dentate gyrus is also found in a high percentage of TLE specimens. The apparent reorganization of mossy fibers from the dentate granule cells is particularly striking, and aberrant innervation of the inner part of the molecular layer by zinc- and dynorphin-containing mossy fibers has been reported in human tissue by several groups of investigators. In a subpopulation of TLE specimens, there is also disorganization of the granule cell layer. Rather than being arranged in the compact, highly organized layer that is characteristic of control tissue, the granule cell bodies in some TLE cases are dispersed. In some additional cases, a bilaminar pattern of granule cells is observed. Each of these changes could contribute to altered circuitry within the dentate gyrus of humans with TLE, and such alterations could influence seizure susceptibility within the hippocampal formation.
Afferent Pathways↗
The effects of lateralized temporal lobe dysfunction on formal and semantic word fluency.
Word fluency performance was studied in 32 patients with unilateral temporal lobe epilepsy (TLE) and 25 healthy dextral controls. Two word fluency tasks were administered conforming to either formal-based criteria or semantic-based criteria. Performance for TLE patients was assessed both pre-operatively and approximately 1 week following anterior temporal lobectomy. Both formal and semantic word fluency decreased regardless of resection laterality. Left TLE patients performed significantly worse at both pre- and post-operative assessments compared to the right TLE patients, while right TLE patients performed significantly poorer than controls on all verbal fluency criteria at pre- and post-operative assessments. In addition, both TLE and control groups produced significantly fewer formal and semantic words during the second 30-sec portion of each task. These findings are discussed in terms of temporal lobe contributions to word fluency production and lexical semantic processing.
Adult↗
Adequacy of language function and verbal memory performance in unilateral temporal lobe epilepsy.
We examined adequacy of language functions, their influence on verbal learning and memory performance, and the relative effects of language function and laterality of seizure focus on the memory performance of 99 left-hemisphere dominant patients with invasively verified epilepsy of left (N = 47) or right (N = 52) temporal lobe origin. Patients with left temporal lobe epilepsy (TLE) scored significantly lower than the right TLE group on several aphasia battery subtests (Visual Naming, Sentence Repetition, Token Test, Reading Comprehension, Aural Comprehension). Adequacy of language function (nominal speech) was significantly related to verbal learning and memory performance for both left and right TLE groups. Finally, comparison of the predictive significance of laterality of TLE and adequacy of language function indicated that language functions (Visual Naming and Aural Comprehension), but not laterality of TLE, were significant predictors for verbal learning and memory performance. It is concluded that: 1) adequacy of basic language functions is particularly compromised in left TLE, 2) there is a significant relationship between adequacy of language function and several aspects of verbal learning and memory ability in both left and right temporal lobe groups, and 3) clinical assessment and theoretical models of memory need to consider these relationships.
Adolescent↗
A long-term follow-up study of first episodes of idiopathic status convulsivus in childhood: in relation to subsequent epilepsy (second report).
Fifty-four idiopathic status convulsivus (SC) cases were followed prospectively for a period between 5 and 21 years, the average being 13 years. Three-fourths of the cases had no residuals. There were two patterns of subsequent epilepsy; 1) complex partial seizures (CPS) with or without secondarily generalization (GTS) developed 4.3 +/- 3.5 years after febrile SC, 2) unilateral seizures or CPS +/- GTS developed 1.2 +/- 1.0 years after afebrile SC. The seizure prognosis of these cases was good except for some cases in the former group. There have been two kinds of theories regarding SC and epilepsy until now. One was derived from retrospective studies: SC and/or complex febrile convulsion (FC) were considered the main causes of temporal lobe epilepsy (TLE) producing mesial temporal sclerosis (MTS). Another was derived from prospective studies, in which the relation between FC and TLE was considered weak. Our results revealed that 6 cases (15%) out of 30 febrile SC developed epilepsy, and that five of those six cases were diagnosed as CPS. Three of 5 CPS cases were diagnosed as TLE. Recently the seizure prognosis of operative therapy for TLE--especially the MTS type--has been very favorable. Furthermore, it has become easy to find MTS by Magnetic Resonance Imaging (MRI). So, we emphasize that a precise follow-up study of SC using MRI, EEG, etc., is important in deciding the appropriate therapy for TLE, as well as in the study of the pathogenesis of TLE.
Child↗
Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epilepsy relief.
It has been reported that hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 +/- 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symptoms. Long-lasting (27 months) normoprolactinemia (19.4 +/- 0.6 ng/ml) and TLE relief were achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 micrograms/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.
Adult↗
Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy.
The distribution of granule cells in the dentate gyrus of the hippocampal formation was studied in control autopsy and temporal lobe epilepsy (TLE) specimens. In control tissue, the granule cell somata were closely approximated and formed a narrow lamina with a distinct, regular border with the molecular layer. In 11 of 15 TLE specimens, the granule cell somata were dispersed and formed a wider than normal granule cell layer. The granule cell somata extended into the molecular layer to varying extents, creating an irregular boundary between the lamina. The dispersed granule cells were frequently aligned in columns, and many of these neurons displayed elongated bipolar forms. The extent of granule cell dispersion appeared to be related to the amount of cell loss in the polymorph layer of the dentate gyrus. Granule cell dispersion was not consistently associated with granule cell loss although 5 of the 11 specimens with granule cell dispersion also showed moderate to marked granule cell loss. The most common features in the histories of the TLE cases with granule cell dispersion were severe febrile seizures or seizures associated with meningitis or encephalitis during the first 4 years of life. The dispersion of the granule cells suggests that there has been some alteration in the patterns of cell migration in a subpopulation of cases with severe TLE. The resultant ectopic positions of the granule cells could lead to changes in both the afferent and efferent connections of these neurons and, thus, contribute to the altered circuitry of the hippocampal formation in TLE.
Adolescent↗
Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.
OBJECTIVE: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. METHODS: 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. RESULTS: No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SIGNIFICANCE: We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.
Adult↗
Temporal lobe epilepsy and aggression.
Research on temporal lobe epilepsy (TLE) and aggression is reviewed in order to learn why it has not contributed more to our understanding of the neural basis of aggression. The research problem can be resolved into two questions: Are temporal lobe epileptics more aggressive? What inferences can be drawn about the factors underlying aggression in TLE? Difficulties in finding suitable operational definitions for TLE and for aggression have, to date, received insufficient attention. In published studies, sample bias and lack of regard for the validity and reliability of behavioral assessments prevent our deciding whether an association exists between interictal aggressive behavior and TLE. Even if this association were demonstrated, one could not draw direct neurobehavioral inferences from it, since a variety of social and psychological, as well as neurophysiological variables could contribute to the association. These would have to be controlled. Methodological refinements could lead to more satisfactory answers to the first question, but the second is considerably more difficult. Some sources of complexity and apparent contradictions in the experimental literature on the neurology of aggression are discussed. They consist of technical problems, the complexity of the neural substrate of aggression and the influence of environmental cues and learning. The combined use of electrophysiological and interview techniques has yielded some interesting results with TLE patients.
Age Factors↗
Substance P: binding to lipids in the brain.
1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered.
Animals↗
Post-ictal recognition memory predicts laterality of temporal lobe seizure focus: comparison with post-operative data.
Standardized verbal and visuo-spatial memory recognition were obtained on 15 patients with unilateral temporal lobe epilepsy (TLE), using a reference group of 43 (12 males, 31 females) subjects with no previous history of neurological disease. Inter-ictal measures on these two tasks failed to differentiate between those patients with left vs right seizure foci. When eight of these patients were tested post-ictally (within 1 hr of seizure), seven showed the expected selective memory impairment when compared to inter-ictal performance. Left TLE patients showed a relative lowering of verbal memory, whereas patients with right TLE showed a relative visuo-spatial memory impairment. A similar result was also found in the patients when a comparison between pre-operative (inter-ictal) and post-operative performance was made, thereby further substantiating the validity of the tasks. This significant association between side of seizure focus and selective impairment of post-ictal memory performance provides evidence of a more direct method of neuropsychological diagnosis in TLE patients prior to surgery.
Adolescent↗
Gamma-aminobutyric acid uptake is decreased in the hippocampus in a genetic model of human temporal lobe epilepsy.
Temporal lobe epilepsy (TLE) is one of the most commonly occurring and most intractable forms of seizure disorders in humans. The fundamental mechanisms underlying the pathogenesis of the disorder have, however, not yet been elucidated. El is an inbred mouse strain with genetic predisposition to epileptic seizures. The El mouse epilepsy shares its main features with TLE in humans and is considered to be an excellent model of the latter. We report a marked decrease in the uptake of gamma-aminobutyric acid (GABA) in the hippocampus of El mice. The data favor the involvement of GABA and the hippocampus in the mechanisms of TLE and suggest a genetic basis for the altered GABA uptake. This is the first report suggesting the possibility of a hereditary defect of a neurotransmitter function in TLE.
Animals↗
Event-related potential (P300) in epilepsy.
The P300 component of auditory event-related potential was studied in 39 patients with temporal lobe epilepsy (TLE), 26 with idiopathic generalized epilepsy (IGE) and 28 controls. The age-corrected P300 latencies were significantly longer in TLE patients compared with those in IGE patients and controls. Neither the duration of epilepsy nor clinical manifestation was related to the P300 component in the same epileptic syndrome. The age-corrected P300 latencies recorded from Cz were significantly prolonged in TLE patients with bilateral temporal EEG foci compared with those with unilateral focus. The effects of anti-epileptic drugs on the P300 component were not significant. Our findings imply that prolonged P300 latency in TLE patients, especially in those with bilateral EEG foci is due to damage of the hippocampus, which is potentially an epileptogenic focus.
Acoustic Stimulation↗
Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy.
Dynorphin A(1-17), an opioid peptide that is normally present in the hippocampal mossy fiber system, was localized immunocytochemically in the hippocampal formation of control autopsy and temporal lobe epilepsy (TLE) specimens. In control tissue, dynorphin-like immunoreactive (Dyn-IR) structures were confined to the mossy fiber path and were most highly concentrated in the polymorph (hilar) region of the dentate gyrus. Very few Dyn-IR structures were present in the molecular and granule cell layers of the dentate gyrus. In contrast, in all TLE specimens, Dyn-IR elements were present in these layers. The extent of aberrant staining varied among the TLE specimens, and 2 major patterns were observed. The first was a relatively wide band of reaction product in the inner one-third to one-fourth of the molecular layer (8 cases), and the second was a more limited distribution of immunoreactive fibers and presumptive terminals in the granule cell and immediately adjacent supragranular regions (2 cases). The extent of aberrant Dyn-IR structures appeared to be related to the amount of cell loss in the polymorph and CA3 fields and to dispersion of the granule cell somata. Specimens processed with the Timm's sulfide silver method for heavy metals provided independent evidence for the distribution of mossy fibers. In both control and TLE specimens, the patterns of labeling were virtually identical to those of dynorphin localization. These findings suggest that sprouting of mossy fibers or their axon collaterals has occurred in hippocampal epilepsy and that the reorganized fibers contain at least one of the neuropeptides that are normally present in this system. Such fibers could form recurrent excitatory circuits and contribute to synchronous firing and epileptiform activity, as suggested in studies of experimental models of epilepsy.
Cell Survival↗
Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.
Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.
TLE↗