Mesial temporal lobe epilepsy case series

From January 2012 to December 2019, the MTLE patients with surgical failure were reviewed, and all patients underwent SEEG-guided reoperation. The epileptogenic network was quantified by calculating FC indicators, including phase slope index (PSI), mutual information (MI) strength, imaginary coherence (icoh), and Granger causality.

Results: Ten patients with 13 seizures were included in the analysis, and 7 of them achived a favorable outcomes after the SEEG-guided reoperation. The surgical zone (SZ) with favorable prognosis showed greater outward information flow than the nonSZ, while the SZ with unfavorable prognosis showed greater inward information flow. The recurrent patients with favorable prognosis had a strong connectivity between the posterior hippocampus, temporal neocortex and insula, while the patients with unfavorable prognosis showed a strong functional connectivity between insula and temporal-parietal-occipital junction. The power spectrum of patients with favorable prognosis was significantly lower than that of patients with unfavorable prognosis, especially showing a more oscillation power of low frequency.

Significance: The SEEG-guided reoperation could achieve favorable seizure control outcomes for recurrent patients.The FCs were a potential indicator to help construct the temporal epileptic network and predictor for the reoperative prognosis in the recurrent patients ¹⁾.

Twenty-seven mTLE patients who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (ILAE Class I) and residual seizures (ILAE Class II-VI). Volumes of the hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. The proportion of cluster volume and number ablated were associated with seizure outcomes.

The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p = 0.013) and number (p = 0.03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p = 0.026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated. (AUC = 0.7670, p = 0.02).

Seizure outcome after LiTT in mTLE patients was significantly associated with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcomes after LiTT in mTLE ²⁾.

Evidence has been provided that the subiculum may play an important role in the generation of seizures.Electrostimulation at this target has been reported to have anticonvulsant effects in kindling and pilocarpine rat models, while in a clinical study of hippocampal deep brain stimulation (DBS), contacts closest to the subiculum were associated with a better anticonvulsive effect.

Vázquez-Barrón et al. evaluated the effect of Electrostimulation of the subiculum in patients with refractory mesial temporal lobe epilepsy (MTLE) who have hippocampal sclerosis (HS).

Six patients with refractory MTLE and HS, who had focal impaired-awareness seizures (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS), had DBS electrodes implanted in the subiculum. During the first month after implantation, all patients were OFF stimulation, then they all completed an open-label follow-up of 24 months ON stimulation. DBS parameters were set at 3 V, 450 µs, 130 Hz, cycling stimulation 1 min ON, 4 min OFF.

There was a mean reduction of 49.16% (±SD 41.65) in total seizure number (FIAS + FBTCS) and a mean reduction of 67.93% (±SD 33.33) in FBTCS at 24 months. FBTCS decreased significantly with respect to baseline, starting from month 2 ON stimulation.

Subiculum stimulation is effective for FBTCS reduction in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS), suggesting that the subiculum mediates the generalization rather than the genesis of mesial temporal lobe seizures. Better results are observed at longer follow-up times ³⁾.

The objectives of a study of Morgan et al. were to identify functional and structural network properties that are associated with early versus long-term seizure outcomes after mesial temporal lobe epilepsy (mTLE) surgery and to determine how these compare to current clinically used methods for seizure outcome prediction.

In this case-control study, 26 presurgical mTLE patients and 44 healthy controls were enrolled to undergo 3-T MRI for functional and structural connectivity mapping across an 8-region network of mTLE seizure propagation, including the hippocampus (left and right), insula (left and right), thalamus (left and right), one midline precuneus, and one midline mid-cingulate. Seizure outcome was assessed annually for up to 3 years. Network properties and current outcome prediction methods related to early and long-term seizure outcome were investigated.

A network model was previously identified across 8 patients with seizure-free mTLE. Results confirmed that whole-network propagation connectivity patterns inconsistent with the mTLE model predict early surgical failure. In those patients with networks consistent with the mTLE network, specific bilateral within-network hippocampal to precuneus impairment (rather than unilateral impairment ipsilateral to the seizure focus) was associated with mild seizure recurrence. No currently used clinical variables offered the same ability to predict long-term outcomes.

It is known that there are important clinical differences between early surgical failure that lead to frequent disabling seizures and late recurrence of less frequent mild seizures. This study demonstrated that divergent network connectivity variability, whole-network versus within-network properties, were uniquely associated with these disparate outcomes ⁴⁾.

Kim et al. aimed in a study were to confirm if selective resection is effective in preserving memory function and identify critical areas for specific memory decline after temporal resection.

In this single-center retrospective study, the authors investigated data from patients who underwent unilateral mesial temporal lobe epilepsy (MTLE) surgery between 2005 and 2015. Data from 74 MTLE patients (60.8% of whom were female; mean [SD] age at surgery 32 years [8.91 years] and duration of epilepsy 16 years [9.65 years]) with histologically proven hippocampal sclerosis were included. Forty-two patients underwent left-sided surgery. The resection area was manually delineated on each patient's postoperative T1-weighted images. Mapping was performed to see if the resected group, compared with the nonresected group, had worse postoperative memory in various memory domains, including verbal items, verbal associative, and figural memory.

Overall, 95.9% had a favorable epilepsy outcome. In verbal item memory, resection of the left lateral temporal area was related to postoperative decline in immediate and delayed recall scores of word lists. In verbal associative memory, resection of the anterior part of the left hippocampus left parahippocampal area, and left lateral temporal area was related to a postoperative decline in immediate recall scores of word pairs. Resection of the posterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to delayed recall scores of the same task. Similarly, in the figural memory, the postoperative decline of immediate recall scores was associated with the resection of the anterior part of the right hippocampus, amygdala, parahippocampal area, and superior temporal area, and decline of delayed recall scores was related to resection of the posterior part of the right hippocampus and parahippocampal area.

Using voxel-based analysis, which accounts for the individual differences in the resection, the authors found a critical region for postoperative memory decline that is not revealed in the region-of-interest or groupwise comparison. Particularly, resection of the hippocampus was related to associative memory. In both verbal and visual memory, resection of the anterior part of the hippocampus was associated with the immediate recall, and resection of the posterior part of the hippocampus was associated with the delayed recall. Therefore, the authors' results suggest that selective resection may be effective in preserving postoperative memory decline ⁵⁾.

Forty-eight patients with MTLE who were managed in the Cerrahpasa Medical Faculty Neurology Department's epilepsy outpatient clinic were recruited for the study. Tests with Sniffin' Sticks and Taste Strips were performed and OBV measured in all patients. Two control groups were recruited, one for the Sniffin' Sticks and Taste Strip tests and one for OBV measurement.

In the smell tests; the threshold, discrimination, and identification scores were significantly lower in the MTLE group than in the control group. The mean taste test scores did not differ significantly between the MTLE and control groups. In the MTLE group, the mean right OBV was 40.2 ± 12.54 and the left OBV was 39.3 ± 10.54, both of which were significantly lower those in the control group. The mean OBVs of patients with hyposmia was significantly smaller bilaterally than the OBVs of those with normosmia. There was no correlation between the gustatory scores and OBV.

Olfactory function was significantly impaired in patients with MTLE compared with healthy controls in all domains, namely threshold, discrimination, and identification. In addition, the olfactory bulb volume was smaller in patients with olfactory dysfunction ⁶⁾.

83 consecutive patients were included within the four groups. Group 1 (seizure-free) consisted of 7 patients, (9%), Group 2 (rare seizures) consisted of 15 patients (18%), Group 3 (often seizures) consisted of 30 patients (36%), and Group 4 (very often seizures) consisted of 31 patients (37%). The groups did not differ significantly in demographic characteristics. There was a strong positive correlation between resistance to therapy and sleep activation on EEG (p = 0.005), occurrence of focal to bilateral seizures (p = 0.007), automatisms (p = 0.004), and the number of previously used antiepileptic drugs (AEDs) (p = 0.002). There was no association between febrile convulsions (FC), hippocampal sclerosis (HS), and the outcome that was found. Conclusion: MTLE is a heterogeneous syndrome. Establishing the factors responsible for, and associated with, drug resistance is important for optimal management and treatment, as early identification of drug resistance should then ensure a timely referral for surgical treatment is made. This prospective study shows that sleep activation on EEG, ictal automatisms, occurrence of focal to bilateral tonic-clonic seizures, and increased number of tried AEDs are negative prognostic factors ⁷⁾.

RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean = 4 seizure/month) versus high (HSF, mean = 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value ö0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE ⁸⁾.

Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), Lam et al. characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site.

Thirty-one unilateral MTLE patients and 30 healthy controls underwent [11 C]ABP688 PET. They compared partial volume corrected [11 C]ABP688 non-displaceable binding potentials (BPND ) between groups using region-of-interest and whole-brain voxel-wise analyses. 18 F fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11 C]ABP688 BPND and [18 F]FDG uptake to compare lateralization and localization differences.

[11 C]ABP688 BPND was focally reduced in the epileptogenic hippocampal head and amygdala (p<0.001). Patients with hippocampal atrophy showed more extensive abnormalities including the ipsilateral temporal neocortex (p=0.006). [11 C]ABP688 BPND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [18 F]FDG uptake, which showed more widespread hypometabolism. Amongst 23/25 operated patients with > 1 year follow-up, 13 were seizure-free (Engel Ia), and showed significantly lower [11 C]ABP688 BPND in the ipsilateral entorhinal cortex.

[11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE ⁹⁾.

18 F-FDG-PET images from 16 patients with Mesial temporal lobe epilepsy (mTLE) were analyzed using local and global metabolic covariance network (MCN) approaches, including whole metabolic pattern analysis (WMPA), hippocampus-based (h-) MCN, whole brain (w-) MCN, and edge-based connectivity analysis (EBCA).

WMPA showed a typical ipsilateral hypometabolism and contralateral hypermetabolism pattern to epileptic zones in mTLE. h-MCN revealed decreased hippocampus-based synchronization in contralateral regions. w-MCN exhibited a disrupted metabolic network with globally increased small-world properties and regionally decreased nodal metrics in the ipsilateral hemisphere. Hippocampus (h)-EBCA and whole brain EBCA (w-EBCA) both detected a reduced-connectivity dominated metabolic covariant network. Moreover, the reduced interhemisphere connectivity seemingly played a major role in the aberrant epileptic topological pattern.

From a metabolic point of view, Wang et al. from the Beijing Neurosurgical Institute, Capital Medical University, Beijing Key Laboratory of Neurostimulation, Department of Neurology, University of Florida, Gainesville, Florida, Department of Nuclear Medicine, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, China, demonstrated the damaging effects with reduced contralateral intranetwork metrics properties and the compensatory effects in contralateral intranetworks with increased network properties. However, the import role of significant reduced interhemisphere connection has rarely been reported in other mTLE studies. Taken together, 18 F-FDG-PET MCN analysis provides new evidence that the mTLE is a system neurological disorder with disrupted networks ¹⁰⁾.

A cohort of 68 unilateral mTLE patients who had achieved an Engel class I outcome postsurgically was studied retrospectively by Mahmoudi et al., from the Neurosurgery Department of Henry Ford Health System, Detroit, Michigan; Qazvin, Tehran Iran. Rochester.

The volumes of multiple brain structures were extracted from preoperative magnetic resonance (MR) images in each. The MR image data set consisted of 54 patients with imaging evidence for hippocampal sclerosis (HS-P) and 14 patients without (HS-N). Data mining techniques (i.e., feature extraction, feature selection, machine learning classifiers) were applied to provide measures of the relative contributions of structures and their correlations with one another. After removing redundant correlated structures, a minimum set of structures was determined as a marker for mTLE lateralization.

Using a logistic regression classifier, the volumes of both hippocampus and amygdala showed correct lateralization rates of 94.1%. This reflected about 11.7% improvement in accuracy relative to using hippocampal volume alone. The addition of thalamic volume increased the lateralization rate to 98.5%. This ternary-structural marker provided a 100% and 92.9% mTLE lateralization accuracy, respectively, for the HS-P and HS-N groups.

The proposed tristructural MR imaging biomarker provides greater lateralization accuracy relative to single- and double-structural biomarkers and thus, may play a more effective role in the surgical decision-making process. Also, lateralization of the patients with insignificant atrophy of hippocampus by the proposed method supports the notion of associated structural changes involving the amygdala and thalamus ¹¹⁾.

Patients (n=106) with refractory MTLE-HS submitted to corticoamygdalohippocampectomy (CAH) (57 left mesial temporal lobe epilepsy (MTLE); 45 males) were enrolled. To determine if the IQ was a predictor of seizure outcome, totally seizure-free (SF) versus nonseizure-free (NSF) patients were evaluated. FreeSurfer was used for cortical thickness and volume estimation, comparing groups with lower (<80) and higher IQ (90-109) levels.

In the whole series, 42.45% of patients were SF (Engel Class 1a; n=45), and 57.54% were NSF (n=61). Total cortical volume was significantly reduced in the group with lower IQ (p=0.01). Significant reductions in the left hemisphere included the following: rostral middle frontal (p=0.001), insula (p=0.002), superior temporal gyrus (p=0.003), thalamus (p=0.004), and precentral gyrus (p=0.02); and those in the right hemisphere included the following: rostral middle frontal (p=0.003), pars orbitalis (p=0.01), and insula (p=0.02). Cortical thickness analysis also showed reductions in the right superior parietal gyrus in patients with lower IQ. No significant relationship between IQ and seizure outcome was found.

This is the first study of a series of patients with pure MTLE-HS, including those with low IQ and their morphometric magnetic resonance imaging (MRI) features using FreeSurfer. Although patients with lower intellectual scores presented more areas of brain atrophy, IQ was not a predictor of surgical outcome. Therefore, when evaluating seizure follow-up, low IQ in patients with MTLE-HS might not contraindicate resective surgery ¹²⁾.

The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36).

There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001).

Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS ¹³⁾.

Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36).

With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome.

The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further ¹⁴⁾.

A certain number of patients suffer significant decline in verbal memory after hippocampectomy. To prevent this disabling complication, a reliable test for predicting postoperative memory decline is greatly desired. Therefore, Tani et al., assessed the value of Electrostimulation of the parahippocampal gyrus (PHG) as a provocation test of verbal memory decline after hippocampectomy on the dominant side.

Eleven right-handed, Japanese-speaking patients with medically intractable left temporal lobe epilepsy (TLE) participated in the study. Before surgery, they underwent provocative testing via Electrostimulation of the left PHG during a verbal encoding task. Their pre- and posthippocampectomy memory function was evaluated according to the Wechsler Memory Scale-Revised (WMS-R) and/or Mini-Mental State Examination (MMSE) before and 6 months after surgery. The relationship between postsurgical memory decline and results of the provocative test was evaluated.

Left hippocampectomy was performed in 7 of the 11 patients. In 3 patients with a positive provocative recognition test, verbal memory function, as assessed by the WMS-R, decreased after hippocampectomy, whereas in 4 patients with a negative provocative recognition test, verbal memory function, as assessed by the WMS-R or MMSE, was preserved.

Results of the present study suggest that Electrostimulation of the PHG is a reliable provocative test to predict posthippocampectomy verbal memory decline ¹⁵⁾.

Eighty patients with temporal lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients' treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death.

At one year, the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group (P<0.001). The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life (P<0.001 for both comparisons) than the patients in the medical group. Four patients (10 percent) had adverse effects of surgery. One patient in the medical group died.

In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy. Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects ¹⁶⁾.