Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Is ‘burned-out hippocampus’ syndrome a distinct electro‐clinical variant of MTLE-HS syndrome?

AimTo study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. ‘burned-out hippocampus’ syndrome (MTLE-BHS).MethodsMTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive “MTLE-BHS” patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison.ResultsSeventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5 ± 7.7 years and the mean duration of epilepsy was18.2 ± 7.3 years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1 year follow-up in 6 and Engel class II outcome in 2.ConclusionAttenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS.     

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy

PurposeTo study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location.MethodsEight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction.ResultsThe distances between active electrode location and estimated ictal onset zone were 11 ± 4.3 or 9.1 ± 2.3 mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N = 6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3 mm from the subiculum (p < 0.05). The 2 non-responders patients were stimulated on contacts located >3 mm to the subiculum.ConclusionDecrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.     

Outcome after cortico-amygdalo-hippocampectomy in patients with temporal lobe epilepsy and normal MRI

RationaleWe describe seizure and neuropsychological outcome obtained after CAH in patients with TLE and normal MRI evaluated in the modern imaging era.MethodsForty-five adult consecutive patients with TLE and normal MRI were studied. All patients had neuropsychological testing, interictal and ictal EEG recordings and MRI. They were divided into two groups: Group 1 (n = 18), included patients in whom non-invasive neurophysiological evaluation was lateralizing and Group 2 (n = 27) included patients with non-lateralizing neurophysiological data who were submitted to invasive recordings.ResultsSeventy-seven percent of the Group 1 patients were rated as Engel I; 11% were rated as Engel II and 11% as Engel III. In Group 2, there were 57% of patients seizure-free, 26% in Engel II and 14% in Engel III. Pre-operatively, mean general IQ was 82 and 78 in Groups1 and 2, respectively; post-operatively, mean general IQ was respectively 86 and 71. Some degree of verbal memory decline was noted in all patients submitted to dominant temporal lobe resection in both Groups 1 and 2. At last follow-up visit, 22% of Group 1 and 11% of Group 2 patients were receiving no antiepileptic drugs (AED).ConclusionsOur data showed that patients with TLE and normal MRI could get good surgical results after CAH although 60% of them would need invasive recordings and their results regarding seizure control and cognition were worse than those obtained in patients with MRI defined temporal lobe lesions. Caution should be taken in offering dominant temporal lobe resection to this subset of patients.     

Recognition of facial emotions and identity in patients with mesial temporal lobe and idiopathic generalized epilepsy: An eye-tracking study

PurposeTo describe visual scanning pattern for facial identity recognition (FIR) and emotion recognition (FER) in patients with idiopathic generalized (IGE) and mesial temporal lobe epilepsy (MTLE). Secondary endpoint was to correlate the results with cognitive function.MethodsBenton Facial Recognition Test (BFRT) and Ekman&Friesen series were performed for FIR and FER respectively in 23 controls, 20 IGE and 19 MTLE patients. Eye movements were recorded by a Hi-Speed eye-tracker system. Neuropsychological tools explored cognitive function.ResultsCorrect FIR rate was 78% in controls, 70.7% in IGE and 67.4% (p = 0.009) in MTLE patients. FER hits reached 82.7% in controls, 74.3% in IGE (p = 0.006) and 73.4% in MTLE (p = 0.002) groups. IGE patients failed in disgust (p = 0.005) and MTLE ones in fear (p = 0.009) and disgust (p = 0.03). FER correlated with neuropsychological scores, particularly verbal fluency (r = 0.542, p < 0.001). Eye-tracking revealed that controls scanned faces more diffusely than IGE and MTLE patients for FIR, who tended to top facial areas. A longer scanning of the top facial area was found in the three groups for FER. Gap between top and bottom facial region fixation time decreased in MTLE patients, with more but shorter fixations in bottom facial region. However, none of these findings were statistically significant.ConclusionFIR was impaired in MTLE patients, and FER in both IGE and MTLE, particularly for fear and disgust. Although not statistically significant, those with impaired FER tended to perform more diffuse eye-tracking over the faces and have cognitive dysfunction.     

Volume,metabolites and neuroinflammation of the hippocampus in bipolar disorder – A combined magnetic resonance imaging and positron emission tomography study

BackgroundThe hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.Materials and methodsTwenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [¹¹C]-(R)-PK11195 neuroinflammation positron emission tomography scan.ResultsIn contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr) + phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA + NAAG concentration, between alcohol use and NAA + NAAG concentration, between microglial activation and the depression score and a negative relation between Cr + PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.ConclusionCompared to HCs, the decreased NAA + NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.     

Detection of hippocampal atrophy in patients with temporal lobe epilepsy: A 3-Tesla MRI shape

In patients with mesial temporal lobe epilepsy (MTLE), brain MRI often detects hippocampal sclerosis (HS). Almost half of patients with MTLE do not show any hippocampal damage on visual or volumetric assessment. Here, we wished to prospectively assess 65 patients with MTLE (41 women, mean age: 39 ± 10 years, range: 21–69; right (12/65 patients) (MRI-negative) nMTLE; right (14/65 patients) (MRI-positive with HS) pMTLE; left (24/65 patients) nMTLE; and left (15/65 patients) pMTLE) using shape analysis (SA). There were significant differences among pMTLE versus nMTLE for age at seizure onset (20.2 ± 12.8 vs. 31.8 ± 16.7 years; p = .0029), duration of epilepsy (14.6 ± 12.7 vs. 21.3 ± 9.6 years; p = .0227), risk of refractoriness (p = .0067), frequency of antecedent febrile convulsions (FCs) (p < .001), as well as a history of epilepsy or FCs (p = .0104). All the subjects underwent the same 3-Tesla MRI protocol. Shape analysis of hippocampal formation was conducted comparing each group versus 44 matched controls.In all four subgroups, SA detected a significant atrophy in the corresponding hippocampus that coincided with the epileptogenic area. The damage was significantly more severe in patients with pMTLE (F value: 5.00) than in subgroups with nMTLE (F value: 3.50) and mainly corresponded to the CA1 subregion and subiculum. In the patients with MTLE, SA detects hippocampal damage that lateralizes with the epileptogenic area. Such damage is most prominent in the CA1 subregion and subiculum that are crucial in the pathogenesis of MTLE.     

Subcortical structural abnormalities in juvenile myoclonic epilepsy (JME): MR volumetry and vertex based analysis

PurposeImaging studies in juvenile myoclonic epilepsy (JME) have shown abnormalities of the thalamus and frontal cortex. The purpose of this study was to systematically investigate the morphological changes in the deep gray matter (GM) structures using techniques of voxel based morphometry (VBM), MR volumetry and shape analysis.MethodologyThe study included 40 patients with JME (M:F = 21:19; age 22.8 ± 5.3 years) and 19 matched controls (M:F = 13:6; age 24.5 ± 4.2 years). All subjects underwent MRI using standard protocol that included T1-3D TFE (Turbo Field Echo) images with 1 mm thickness. VBM analysis and MR volumetry were performed. The volumes of deep subcortical GM structures were extracted and vertex-wise shape analysis was performed using FSL-FIRST (FSL-Integrated Registration and Segmentation Toolbox) software.ResultsVBM analysis with a thalamic mask revealed focal thalamic alterations in the anteromedial aspect of the thalamus (p < 0.05, false discovery rate (FDR) corrected) which remained significant after adjusting for age, gender and intracranial volume (ICV). Significant volume loss was noted in both the thalami. Vertex-wise shape analysis showed significant focal surface reductions in the thalami bilaterally in patients that were predominantly seen in the medial as well as lateral aspects of the thalamus (p < 0.05, FDR corrected). The disease duration correlated with left hippocampus volume while age of onset correlated with right hippocampus volume.ConclusionsThis study confirms the presence of thalamic alterations in patients with JME. Shape analysis technique provided complementary information and disclosed the presence of focal atrophic changes in patients’ thalami. The striatum and hippocampus did not show any significant alterations.     

Long-term outcome and predictors of resective surgery prognosis in patients with refractory extratemporal epilepsy

PurposeWe analyzed the long-term postoperative outcome and possible predictive factors of the outcome in surgically treated patients with refractory extratemporal epilepsy.MethodsWe retrospectively analyzed 73 patients who had undergone resective surgery at the Epilepsy Center Brno between 1995 and 2010 and who had reached at least 1 year outcome after the surgery. The average age at surgery was 28.3 ± 11.4 years. Magnetic resonance imaging (MRI) did not reveal any lesion in 24 patients (32.9%). Surgical outcome was assessed annually using Engel's modified classification until 5 years after surgery and at the latest follow-up visit.ResultsFollowing the surgery, Engel Class I outcome was found in 52.1% of patients after 1 year, in 55.0% after 5 years, and in 50.7% at the last follow-up visit (average 6.15 ± 3.84 years). Of the patients who reached the 5-year follow-up visit (average of the last follow-up 9.23 years), 37.5% were classified as Engel IA at each follow-up visit. Tumorous etiology and lesions seen in preoperative MRI were associated with significantly better outcome (p = 0.035; p < 0.01). Postoperatively, 9.6% patients had permanent neurological deficits.ConclusionSurgical treatment of refractory extratemporal epilepsy is an effective procedure. The presence of a visible MRI-detected lesion and tumorous etiology is associated with significantly better outcome than the absence of MRI-detected lesion or other etiology.     

Quantification of subfield pathology in hippocampal sclerosis: A systematic review and meta-analysis

BackgroundThe utility of MRI-based hippocampal subfield volumetry as a diagnostic test for hippocampal sclerosis (HS) is based on the hypothesis that specific hippocampal subfields are differentially affected in HS. While qualitative studies suggest selective involvement of certain hippocampal subfields in this condition, whether quantifiable differences exist remains unclear. Neuronal density measurement is the most widely used technique for measuring subfield pathological change in HS. Therefore, a systematic review and meta-analysis of studies reporting neuronal densities in temporal lobe epilepsy was performed in order to quantify subfield pathology in hippocampal sclerosis.MethodsStudies were identified by searching the Medline and Embase databases using the search terms: cell count, hippocampus, and epilepsy. Of the 192 studies identified by the literature search, seven met all inclusion and exclusion criteria. Random effects meta-analyses were performed, comparing: (i) neuronal densities in control (n = 121) versus HS (n = 371) groups for subfields CA1-4; and (ii) amount of neuronal loss in HS between subfields CA1-4.ResultsStatistically significant neuronal loss was observed comparing HS to control groups in all subfields CA1-4 (p < 0.001 for all comparisons). Significantly greater neuronal loss was demonstrated in HS comparing CA1 versus CA2 (p < 0.001), CA3 (p = 0.005), and CA4 (p = 0.003). Greater pyramidal cell loss was also demonstrated in CA3 relative to the CA2 subfield (p = 0.003). No significant differences were identified comparing CA2 and CA4 (p = 0.39); or comparing CA3 and CA4 (p = 0.64).ConclusionsHS is characterized by pathology in all hippocampal subfields. Quantifiable differences exist in the involvement of specific hippocampal subfields in HS. Neuronal loss is greatest in CA1, intermediate in CA3 and CA4, and least in CA2. Further studies are required to determine if this pattern can be detected using in vivo MRI.     

T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI

BackgroundIncreased MRI T2 signal is commonly present not only in the hippocampus but also in other temporal structures of patients with temporal lobe epilepsy (TLE), and it is associated with histological abnormalities related to the epileptogenic lesion.ObjectiveThis study aimed to verify the distribution of T2 increased signal in temporal lobe structures and its correlations with clinical characteristics of TLE patients with (TLE-HS) or without (TLE-NL) MRI signs of hippocampal sclerosis.MethodsWe selected 203 consecutive patients: 124 with TLE-HS and 79 with TLE-NL. Healthy controls (N = 59) were used as a comparison group/comparative group. T2 multiecho images obtained via a 3-T MRI were evaluated with in-house software. T2 signal decays were computed from five original echoes in regions of interest in the hippocampus, amygdala, and white matter of the anterior temporal lobe. Values higher than 2 standard deviations from the mean of controls were considered as abnormal.ResultsT2 signal increase was observed in the hippocampus in 78% of patients with TLE-HS and in 17% of patients with TLE-NL; in the amygdala in 13% of patients with TLE-HS and in 14% of patients with TLE-NL; and in the temporal lobe white matter in 22% of patients with TLE-HS and in 8% of patients with TLE-NL. Group analysis demonstrated a significant difference in the distribution of the T2 relaxation times of the hippocampus (ANOVA, p < 0.0001), amygdala (p = 0.003), and temporal lobe white matter (p < 0.0001) ipsilateral to the epileptogenic zone for patients with TLE-HS compared with controls but only for the amygdala (p = 0.029) and temporal lobe white matter (ANOVA, p = 0.025) for patients with TLE-NL compared with controls. The average signal from the hippocampus ipsilateral to the epileptogenic zone was significantly higher in patients with no family history of epilepsy (two-sample T-test, p = 0.005).ConclusionIncreased T2 signal occurs in different temporal structures of patients with TLE-HS and in patients with TLE-NL. The hippocampal hyperintense signal is more pronounced in patients without family history of epilepsy and is influenced by earlier seizure onset. These changes in T2 signal may be associated with structural abnormalities related to the epileptogenic zone or to the nature of the initial precipitating injury in patients with TLE.     

Atypical handedness in mesial temporal lobe epilepsy

ObjectiveThe main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population.MethodsHandedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated.ResultsWe found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p = 0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8 years of age [median; min-max 0.5–17] in left-handers versus 15 years of age [median; min-max 3–30] in right-handers (p < 0.001).ConclusionsLeft-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.     

Predictors of intellectual functioning after epilepsy surgery in childhood: The role of socioeconomic status

ObjectiveThe objective of this study was to evaluate the association between socioeconomic status and intellectual functioning in children with medically refractory epilepsy, before and after resective epilepsy surgery. Family environment is a strong contributor to cognitive development in children and has been recently shown to play a significant role in intellectual outcome after surgery in children with epilepsy.MethodsOne hundred children who had undergone resective epilepsy surgery and completed preoperative and postoperative assessments of IQ as part of clinical care were included in the study. We evaluated the impact of epilepsy-related variables, income quintile, and residence location on IQ.ResultsGreater improvements in IQ after surgery were associated with an older age at surgery (β = .235, p = .018). Higher IQ scores at follow-up were associated with an older age of seizure onset (β = .371, p < .001), older age at surgery (β = .356, p < .001), unilobar epileptogenic focus (β = .394, p < .001), and mesial temporal sclerosis (β = .338, p = .001) or tumor (β = .457, p < .001) in comparison with malformation of cortical development; age at seizure onset did not remain as a significant predictor in multivariable regression analysis. Income quintile, residence location, seizure control, and antiepileptic medication use were not significant predictors.ConclusionsEpilepsy-related variables were the strongest predictors of IQ and postoperative change in IQ. We were unable to identify a significant association between IQ and socioeconomic status. Future research should evaluate the impact of multiple aspects of family environment.     

The amygdala and anxiety after epilepsy surgery

The relationship between amygdalar volume and anxiety after epilepsy surgery was explored. Participants comprised patients who underwent mesial temporal (n = 26) or non-mesial temporal resections (n = 16) and 41 neurologically normal controls. Anxiety was prospectively measured preoperatively and for the first 12 months postoperatively using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Amygdalar volumetry was performed on preoperative and control T1-weighted MRI scans. Resection of an ipsilateral amygdala of normal volume, relative to controls, was associated with postoperative anxiety in patients with mesial temporal resections, regardless of seizure outcome [F(1, 22) = 5.17, P < 0.05]. There was no relationship between amygdalar volume and anxiety in patients with non-mesial temporal resections, or between contralateral amygdalar volume and anxiety in patients with mesial temporal resections (P > 0.05 for all comparisons). In conclusion, resection or deafferentation of an amygdala with a volume within the normal range was associated with increased postoperative anxiety.     

Electrocorticographic evidence and surgical implications of different physiopathologic subtypes of temporal epilepsy

ObjectiveMesial temporal lobe epilepsy (MTLE) might have a focal or a network physiopathology. Therefore, the objective of this study was to demonstrate that changes in the spiking activity during electrocorticography (ECoG) could reflect changes in the epileptic network, and the resection of the epileptogenic zone could eliminate the mesial spikes.MethodsTwenty-five MTLE patients were intraoperatively evaluated by ECoG and the mesial strip was maintained until the lateral cortectomy (LC) was completed. Total spiking activity (TSA, mean spikes/min for all the mesial channels) was computed off-line before and after LC. Either a tailored anterior medial temporal resection or LC was carried out based on the TSA changes.ResultsThe outcome at 19.1 ± 1.4 months was Engel’s class I, 84%; II, 8%; or III, 8%. During the LC, the TSA recorded from the mesial strip did not change in 14 patients, increased in three patients, and decreased in eight patients. In 20% of patients, the mesial activity completely disappeared, and the mesial structures were spared. All of these patients were Engel’s class IA.ConclusionsOur results strongly suggest the existence of physiopathologic differences in MTLE. The identification of these subtypes is fundamental for an individualized surgical approach.SignificanceECoG would be needed to offer a better surgical approach.     

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis

ObjectiveThe objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield.MethodsThe 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).ResultsThere 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).SignificanceCornu 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.     

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center

BackgroundHemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy.MethodsSeven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames.ResultsThe mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p = 0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p = 0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p = 0.044). Adult and pediatric populations did not differ significantly in any tested variable.ConclusionsHemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.     

Relationships between ophthalmic artery flow direction and cognitive performance in patients with unilateral carotid artery stenosis

BackgroundCerebral hypoperfusion is responsible for cognitive impairment in patients with severe carotid artery stenosis (CAS). The manifestation of reversed ophthalmic artery flow (ROAF) is not uncommon in patients with CAS, suggesting a state of intensified cerebral hypoperfusion. This study aimed to examine whether the presence of ROAF can exacerbate cognitive impairment in patients with severe unilateral CAS.MethodsOne-hundred-and-two patients with CAS and 37 age-matched volunteers participated in this case–control study. Depending on the side of CAS and occurrences of ROAF, the patients were allocated to four groups: left CAS groups with ROAF (n = 28) or without ROAF (n = 22), and right CAS groups with ROAF (n = 26) or without ROAF (n = 26). All subjects underwent a battery of neuropsychological tests.ResultsAll patients performed worse than the control group on most tests. No significant differences were observed between patient groups (ps > 0.05), except for inferior performance on psychomotor speed and visuospatial tests in the right ROAF group (ps < 0.03). Hierarchical regression analyses indicated strong contributions of estimated premorbid intelligence to performance on most tests (ps < 0.05). The severity of left and right CAS was distinctively associated with different functions. To a lesser extent, the severity of infarcts was also associated with impairment of psychomotor speed and some executive functions (ps < 0.05). The contributions of ROAF to performance on most tests were negligible.ConclusionPatients with unilateral CAS may present with specific cognitive impairment relevant to the ipsilateral hemispheric functions. However, the manifestation of ROAF does not necessarily imply more extensive or severe cognitive impairment.     

BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a functionally relevant single nucleotide polymorphism affecting the secretion of BDNF and is implicated in differences in hippocampal volumes.MethodsThis is a systematic meta-analytical review of findings from imaging genetic studies on the impact of the rs6265 SNP on hippocampal volumes in neuropsychiatric patients with major depressive disorder, anxiety, bipolar disorder or schizophrenia.ResultsThe overall sample size of 18 independent clinical cohorts comprised 1695 patients. Our results indicated no significant association of left (Hedge's g = 0.08, p = 0.12), right (g = 0.07, p = 0.22) or bilateral (g = 0.07, p = 0.16) hippocampal volumes with BDNF rs6265 in neuropsychiatric patients. There was no evidence for a publication bias or any demographic, clinical, or methodological moderating effects.Both Val/Val homozygotes (g = 0.32, p = 0.004) and Met-carriers (g = 0.20, p = 0.004) from the patient sample had significantly smaller hippocampal volumes than the healthy control sample with the same allele. The magnitude of these effects did not differ between the two genotypes.ConclusionThis meta-analysis suggests that there is no association between this BDNF polymorphism and hippocampal volumes. For each BDNF genotype, the hippocampal volumes were significantly lower in neuropsychiatric patients than in healthy controls.     

Cognitive functions in children exposed to antiepileptic drugs in utero - Study in Georgia

ObjectiveThe cognitive teratogenicity of antiepileptic drugs (AEDs) has gained increasing attention in the last decade. The objective of the current study was to assess the effects of AED fetal exposure on the cognitive development of children of mothers with epilepsy from Georgia in a controlled study taking into consideration major confounding factors.MethodsA prospective cohort group was formed from children and mothers registered in the Georgian National AED-Pregnancy Registry. The study group's age- and gender-matched control children without fetal AED exposure were selected retrospectively. The Intelligence Quotient (IQ) using the Wechsler Adult Intelligence Scale – revised (WAIS-R) was assessed in mothers. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-4) were used to assess intellectual functioning for children of both study and control groups. Linear regression analysis was performed to detect association of AED exposure on the cognitive performance of children.ResultsIn total, 100 children aged 36 to 72 months were evaluated. The IQ of WWE was significantly lower compared to women without epilepsy in all modalities. Exposure to valproate (VPA) (n = 18) was associated with lowest cognitive performance regarding Full Scale IQ (FSIQ) (β, − 12.04; p = 0.006) and verbal comprehension (VCI) (β, − 8.89; p = 0.019). Maternal FSIQ, maternal performance IQ (PIQ), and child's age at first phrases were independent factors associated with the cognitive development of children.ConclusionsMultivariate analysis showed VPA to be an independent predictor for decreased cognitive performance. Maternal FSIQ, PIQ, and child developmental achievements were significant confounders for cognitive performance in children.