Neuroethology application for the study of human temporal lobe epilepsy: from basic to applied sciences.

The aim of this investigation was to apply neuroethology to the study of human temporal lobe epilepsy (TLE). For this purpose, 42 seizures in 7 patients recorded during video/EEG monitoring (1997-1998) were analyzed by means of a behavioral glossary containing all behaviors. Video recordings were reobserved, and all patients' behaviors were annotated second-by-second. Data were analyzed using Ethomatic software and displayed as flowcharts including frequency, mean duration, and sequential statistic interaction of behavioral items (chi2 > or = 10.827, P<0.001). Flowcharts of (1) a group of seizures from a single patient, (2) the sum of four seizures per patient of two patients with right and five patients with left TLE, and (3) the comparison of left versus right TLE are shown. Well-established data in the literature were confirmed, such as aura (especially epigastric), contralateral lateralization value of dystonia and version, consciousness and language alterations in ictal and postictal periods, mostly with respect to dominant hemisphere involvement, among others. Less well established data such as awakening seizures in TLE patients, lateralization value of facial wiping (ipsilateral to the focus), statistically significant associations between behavioral pairs (dyads), and new behavioral sequences in TLE were also observed. We suggest that neuroethology also has great potential in the study of human epilepsy semiology. This work had an important role in method standardization for human epilepsy, setting the basis for the development of future clinical studies including correlation with other diagnostic methods (EEG, magnetic resonance, and SPECT). The next step will be the comparative study of seizures of patients with left and right TLE, with a greater number of patients, and the development of a digital video library.

Suppression of obsessive-compulsive symptoms after epilepsy surgery.

We report two male patients with medically intractable epilepsy and obsessive-compulsive disorder (OCD) symptoms. Both patients experienced remission of obsessive-compulsive symptoms after surgical treatment of epilepsy. Although the surgeries targeted different brain regions, the two patients had in common unilateral anterior cingulate cortex ablation. On the basis of these observations, we discuss the pathophysiology of OCD symptoms, emphasizing the role of corticosubcortical pathways in their genesis. Our data suggest that surgeries that affect neural loops associated with obsessive-compulsive symptoms can lead to an improvement of OCD; however, the structures responsible for this effect cannot be conclusively determined.

Cognitive performance of patients with mesial temporal lobe epilepsy and incidental calcified neurocysticercosis.

OBJECTIVES: Although chronic calcified neurocysticercosis (NCC) has been considered a major cause of symptomatic epilepsy in developing countries, it can also be an incidental pathological finding in epileptic patients from endemic regions. The mechanisms of brain plasticity occurring in patients with NCC during and after the inflammatory process related to the parasite infection, death, degeneration, and calcification within the host brain might be an independent factor for cognitive impairment in patients with NCC and epilepsy. In order to assess this possibility cognitive performance of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) with and without NCC was investigated through structured neuropsychological testing. METHODS: Cognitive performance of long term MTLE-HS patients with (HS-NCC group, n = 32) and without NCC (HS only, n = 48) was compared. Imbalances between the two groups with respect to clinical, demographic, neuroimaging, and electrophysiological variables were adjusted by linear multiple regression analysis and Bonferroni correction for multiple tests. RESULTS AND CONCLUSIONS: There were no cognitive performance differences between HS-NCC and HS only patients, leading to the conclusion that chronic calcified NCC per se does not aggravate the cognitive performance of patients with long term MTLE-HS.

Cortical malformations are associated with a rare polymorphism of cellular prion protein.

Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal excitability in vitro and increased sensitivity to seizures in vivo. The authors previously reported a rare polymorphism at codon 171 (Asn-->Ser) of human Prnp to be associated with mesial temporal lobe epilepsy related to hippocampal sclerosis. They demonstrated that the same variant allele is also associated with symptomatic epilepsies related to different forms of malformations of cortical development.

Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant.

BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.

Accuracy of ictal SPECT in mesial temporal lobe epilepsy with bilateral interictal spikes.

OBJECTIVE: In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semiology and ictal EEG is better for patients with unilateral interictal spikes (UIS) than for patients with bilateral interictal spikes (BIS), possibly due to rapid seizure propagation patterns associated with bilateral epileptogenesis. In this study, the authors investigated if ictal SPECT is a reliable diagnostic test for both UIS and BIS patients. METHODS: Video-EEG recording was used as the gold standard to examine the accuracy of ictal SPECT and its relationship with interictal and ictal EEG. Ninety-three consecutive patients with MTLE associated with hippocampal sclerosis were included in the analysis. Ictal SPECT was considered accurate if two blinded observers independently lateralized the scan correctly. RESULTS: Ictal SPECT correctly lateralized 75 (80.6%) of 93 scans. The rate of correct seizure lateralization was 87.6% for the UIS group and only 55.0% for the BIS group (p = 0.0027). In the EEG epochs, 66.7% of BIS patients vs 43.4% of UIS patients had nonlateralized ictal EEG (p < 0.001). CONCLUSION: The authors conclude that the accuracy of ictal SPECT is worse for MTLE patients with BIS than for those with UIS. The role of ictal SPECT in presurgical evaluation of patients with BIS must be reviewed.

Loss and sprouting of nitric oxide synthase neurons in the human epileptic hippocampus.

PURPOSE: Nitric oxide (NO) has been implicated in a variety of functions, including the control of synaptic plasticity and sensory signaling. Current evidence suggests that this unconventional neurotransmitter mediates N-methyl-d-aspartate (NMDA) receptor-linked excitotoxicity. This study describes the expression of neuronal NO synthase (nNOS) immunoreactivity (IR) in hippocampi from patients with temporal lobe epilepsy (TLE). METHODS: Hippocampi from patients with clinical symptoms, neuroimaging, and EEG typical of hippocampal sclerosis (HS; n = 22) were compared with those from patients with neocortical temporal lesions (NONHS; n = 4) and autopsy (AUT; n = 18) patients for total cells, and nNOS-IR neuron and puncta densities. RESULTS: Compared with AUT, HS hippocampi had significantly less nNOS-IR neuron densities in the fascia dentata (FD); hilus, and CA4, CA3, CA2, and CA1 subfields. HS hippocampi had significantly greater nNOS-IR puncta densities in the FD, as compared with AUT and NONHS. CONCLUSIONS: Our results show that hippocampi from TLE patients exhibit a loss of nNOS-IR neurons and an abnormal FD innervation. The release of NO can influence the dynamics of ionic channels and neurotransmitter release, thus affecting neuronal membrane potential. Because the NOergic transmission does not obey the topographic constraints imposed on conventional transmitters, target cells can be stimulated even in regions with severe deafferentation. The plastic changes described here may contribute to abnormal hippocampal excitability.

Typical and atypical perfusion patterns in periictal SPECT of patients with unilateral temporal lobe epilepsy.

PURPOSE: To characterize perfusion patterns of periictal single-photon emission tomography (SPECT) in patients with unilateral temporal lobe epilepsy (TLE) and to determine their relationship to the epileptogenic zone (EZ). METHODS: We studied periictal SPECT scans of 53 patients after anterior mesial temporal lobectomy who had good seizure outcome after surgery. Ictal SPECT scans were performed during video-EEG monitoring. Typical SPECT patterns consisted of ipsilateral ictal hyperperfusion or ipsilateral postictal hypoperfusion. Atypical ictal patterns included normal scans, bilateral temporal hyperperfusion, or contralateral patterns. These perfusion patterns were retrospectively analyzed searching for concordance rate with the EZ. RESULTS: We obtained 51 ictal and two early postictal scans. In the typical group, 40 (75.4%) patients had ipsilateral ictal temporal lobe hyperperfusion, and one (1.9%) patient had ipsilateral postictal temporal lobe hypoperfusion. Twelve (22.7%) patients exhibited atypical perfusion patterns: seven (13.2%) patients had bitemporal ictal hyperperfusion (four cases showed asymmetric temporal lobe changes), four (7.6%) patients had contralateral hyperperfusion, and one (1.9%) patient had a normal SPECT scan. All four patients with bitemporal asymmetric hyperperfusions showed greater perfusion lateralized to the side of the EZ. Three of the four patients who had contralateral hyperperfusion also had a complex postictal-like pattern in the ipsilateral temporal lobe consisting of anteromesial hyperperfusion with adjacent lateral hypoperfusion. CONCLUSIONS: This study analyzed typical and atypical perfusion patterns in unilateral TLE, and suggested that not only typical, but also some atypical perfusion patterns may contribute to the lateralization of EZ.

Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy.

BACKGROUND: Several studies suggest that neurocysticercosis is the main cause of symptomatic epilepsy in developing countries. In such areas, calcified cysticercotic lesions (CCL) are frequently found in patients with complex partial seizures associated with hippocampal sclerosis (HS). The authors studied whether there are clinical and pathologic differences between HS patients with and without CCL. METHODS: The authors determined the clinical and pathologic findings of 30 patients with HS and compared them with 32 patients with HS + CCL. Hippocampi from both groups were measured for fascia dentata Timm staining and cell density in hippocampal subfields. RESULTS: In the HS + CCL group, single or multiple CCL were found in all lobes with no lobar predominance. An initial precipitating event occurred in 83.3% of HS and in 62.5% of HS + CCL. First complex partial seizure occurred at 10.1 years in HS and at 11.9 years in HS + CCL. No significant differences were found for fascia dentata Timm staining and hippocampal cell densities. Good postsurgery outcome (Engel I classification) did not differ between groups, with this result occurring in 76.6% of patients with HS and 81.2% of patients with HS + CCL. CONCLUSIONS: The presence of CCL does not influence the clinical and pathologic profile of patients with hippocampal atrophy. Clinical histories and postsurgical outcomes were similar to those of patients with classic HS, suggesting that the CCL is probably, in this set of patients, a coincidental pathology and does not have a role in epileptogenesis.