Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co-morbidities

Psychiatric co-morbidities in epilepsy are common in patients with temporal lobe epilepsy (TLE). Pathological alterations in TLE are well characterised; however, neuropathologic data are relatively scale regarding the association between psychiatric diseases and epilepsy. Our objective was to evaluate the clinical data of 46 adult TLE patients with and without psychiatric co-morbidities and to correlate the data with hippocampal neuronal density and mossy fiber sprouting. Accordingly, patients were grouped as follows: TLE patients without history of psychiatric disorder (TLE, n = 16), TLE patients with interictal psychosis (TLE + P, n = 14), and TLE patients with major depression (TLE + D, n = 16). Hippocampi from autopsies served as non-epileptic controls (n = 10). TLE + P exhibited significantly diminished mossy fiber sprouting and decreased neuronal density in the entorhinal cortex when compared with TLE. TLE + P showed significantly poorer results in verbal memory tasks. TLE + D exhibited significantly increased mossy fiber sprouting length when compared with TLE and TLE + P. Further, a higher proportion of TLE + D and TLE + P presented secondarily generalised seizures than did TLE. Our results indicate that TLE patients with psychiatric disorders have distinct features when compared with TLE patients without psychiatric co-morbidities and that these changes may be involved in either the manifestation or the maintenance of psychiatric co-morbidities in epilepsy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

The occipital lobe convexity sulci and gyri

Object. The anatomy of the occipital lobe convexity is so intricate and variable that its precise description is not found in the classic anatomy textbooks, and the occipital sulci and gyri are described with different nomenclatures according to different authors. The aim of this study was to investigate and describe the anatomy of the occipital lobe convexity and clarify its nomenclature. Methods. The configurations of sulci and gyri on the lateral surface of the occipital lobe of 20 cerebral hemispheres were examined in order to identify the most characteristic and consistent patterns. Results. The most characteristic and consistent occipital sulci identified in this study were the intraoccipital, transverse occipital, and lateral occipital sulci. The morphology of the transverse occipital sulcus and the intraoccipital sulcus connection was identified as the most important aspect to define the gyral pattern of the occipital lobe convexity. Conclusions. Knowledge of the main features of the occipital sulci and gyri permits the recognition of a basic configuration of the occipital lobe and the identification of its sulcal and gyral variations. (http://thejns.org/doi/abs/10.3171/2012.1.JNS11978)

Supracerebellar transtentorial approach-resection of the tentorium instead of an opening-to provide broad exposure of the mediobasal temporal lobe: anatomical aspects and surgical applications Clinical article

Object. The aim of this study was to describe the surgical anatomy of the mediobasal aspect of the temporal lobe and the supracerebellar transtentorial (SCTT) approach performed not with an opening, but with the resection of the tentorium, as an alternative route for the neurosurgical management of vascular and tumoral lesions arising from this region. Methods. Cadaveric specimens were used to illustrate the surgical anatomy of the mediobasal region of the temporal lobe. Demographic aspects, characteristics of lesions, clinical presentation, surgical results, follow-up findings, and outcomes were retrospectively reviewed for patients referred to receive the SCTT approach with tentorial resection. Results. Ten patients (83%) were female and 2 (17%) were male. Their ages ranged from 6 to 59 years (mean 34.5 +/- 15.8 years). All lesions (3 posterior cerebral artery aneurysms, 3 arteriovenous malformations, 3 cavernous malformations, and 3 tumors) were completely excluded or resected. After a mean follow-up period of 143 months (range 10-240 months), the mean postoperative Glasgow Outcome Scale score was 4.9. Conclusions. Knowledge of the surgical anatomy provides improvement for microsurgical approaches. The evolution from a small opening to a resection of the tentorium absolutely changed the exposure of the mediobasal aspect of the temporal lobe. The SCTT approach with tentorial resection is an excellent alternative route to the posterior part of mediobasal aspect of the temporal lobe, and it was enough to achieve the best neurosurgical management of tumoral and vascular lesions located in this area. (http://thejns.org/doi/abs/10.3171/2011.12.JNS111256)

Psychiatric comorbidities in temporal lobe epilepsy: Possible relationships between psychotic disorders and involvement of limbic circuits

Objective: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. Methods: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABAA (subunits a1, beta 1, beta 2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in a1, beta 1, and beta 2 subunits of GABAA receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. (C) 2010 Wiley Periodicals, Inc., Inc.

Pathophysiology of mood disorders in temporal lobe epilepsy

Objective: There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. Methods: In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.

New records of the harlequin frog Atelopus nahumae RUIZ-CARRANZA, ARDILA-ROBAYO & HERNANDEZ-CAMACHO, 1994, in the Sierra Nevada de Santa Marta (Colombia), with notes of its distribution (Anura: Bufonidae)

The known distribution of the harlequin frog, Atelopus nahumae RUIZ-CARRANZA, ARDILA-ROBAYO & HERNANDEZ-CAMACHO, 1994, is reported along with three new locality records in the northwestern Sierra Nevada de Santa Marta (Colombia). In the new localities, observations were made on the frog's mating behavior. This report adds the Cordoba River Basin, another high valley of the Sierra Nevada de Santa Marta, to the known range of A. nahumae. Nevertheless, the general distribution of the species in this region is largely unknown.

Memory in children with temporal lobe epilepsy is at least partially explained by executive dysfunction

An association between memory and executive dysfunction (ED) has been demonstrated in patients with mixed neurological disorders. We aimed to investigate the impact of ED in memory tasks of children with temporal lobe epilepsy (TLE). We evaluated 36 children with TLE and 28 controls with tests for memory, learning, attention, mental flexibility, and mental tracking. Data analysis was composed of comparison between patients and controls in memory and executive function; correlation between memory and executive function tests; and comparison between patients with mild and severe ED in memory tests. Children with TLE had worse performance in focused attention, immediate and delayed recall, phonological memory, mental tracking, planning, and abstraction. Planning, abstraction, and mental tracking were correlated with visual and verbal memory. Children with severe ED had worse performance in verbal and visual memory and learning tests. This study showed that ED was related to memory performance in children with TLE. (C) 2012 Elsevier Inc. All rights reserved.

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy

Purpose: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. Methods: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. Results: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=.1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R. = 2.9; 95% C.I. = 1.1-7.7; p=0.033); normal MRI (H.R. = 4.8; 95% C.I. = 1.4-16.6; p = 0.012), and MRI with lesion involving eloquent cortex (H.R. = 3.8; 95% C.I. = 1.2-12.0; p = 0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. Conclusion: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series. (C) 2011 Elsevier B.V. All rights reserved.

On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship?

Neurocysticercosis (NCC) and mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) are two common worldwide forms of focal epilepsy. In regions where NCC is endemic, both diseases can be observed in the same patient. There is recent and growing evidence suggesting that NCC might contribute to or even cause MTLE-HS. In this article, we review the literature regarding NCC and temporal lobe epilepsy, specifically addressing the relationship between NCC and MTLE-HS. In addition, we review some scenarios where NCC seems to emerge as a causative agent or contributor to the development of MTLE-HS in some patients. This association is important because it may have an impact on the evaluation and treatment of a sizable proportion of patients with epilepsy. Insights from these clinical observations might also contribute to the understanding of the neurobiology of both NCC and MTLE-HS. We hope that our review might shed some light on this interesting interplay between two of the most common worldwide conditions associated with human focal epilepsy.

Surgical and postmortem pathology studies: contribution for the investigation of temporal lobe epilepsy

Pathology studies in epilepsy patients bring useful information for comprehending the physiopathology of various forms of epilepsy, as well as aspects related to response to treatment and long-term prognosis. These studies are usually restricted to surgical specimens obtained from patients with refractory focal epilepsies. Therefore, most of them pertain to temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and malformations of cortical development (MCD), thus providing information of a selected group of patients and restricted regions of the brain. Postmortem whole brain studies are rarely performed in epilepsy patients, however they may provide extensive information on brain pathology, allowing the analysis of areas beyond the putative epileptogenic zone. In this article, we reviewed pathology studies performed in epilepsy patients with emphasis on neuropathological findings in TLE with MTS and MCD. Furthermore, we reviewed data from postmortem studies and discussed the importance of performing these studies in epilepsy populations.

Psychiatric comorbidities in temporal lobe epilepsy: possible relationships between psychotic disorders and involvement of limbic circuits

OBJECTIVE: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. METHODS: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. CONCLUSIONS: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

Wavelet analysis of heart rate variability related to nocturnal frontal lobe epilepsy seizures

Introduction: Nocturnal frontal lobe epilepsy (NFLE) is a distinct syndrome of partial epilepsy whose clinical features comprise a spectrum of paroxysmal motor manifestations of variable duration and complexity, arising from sleep. Cardiovascular changes during NFLE seizures have previously been observed, however the extent of these modifications and their relationship with seizure onset has not been analyzed in detail. Objective: Aim of present study is to evaluate NFLE seizure related changes in heart rate (HR) and in sympathetic/parasympathetic balance through wavelet analysis of HR variability (HRV). Methods: We evaluated the whole night digitally recorded video-polysomnography (VPSG) of 9 patients diagnosed with NFLE with no history of cardiac disorders and normal cardiac examinations. Events with features of NFLE seizures were selected independently by three examiners and included in the study only if a consensus was reached. Heart rate was evaluated by measuring the interval between two consecutive R-waves of QRS complexes (RRi). RRi series were digitally calculated for a period of 20 minutes, including the seizures and resampled at 10 Hz using cubic spline interpolation. A multiresolution analysis was performed (Daubechies-16 form), and the squared level specific amplitude coefficients were summed across appropriate decomposition levels in order to compute total band powers in bands of interest (LF: 0.039062 - 0.156248, HF: 0.156248 - 0.624992). A general linear model was then applied to estimate changes in RRi, LF and HF powers during three different period (Basal) (30 sec, at least 30 sec before seizure onset, during which no movements occurred and autonomic conditions resulted stationary); pre-seizure period (preSP) (10 sec preceding seizure onset) and seizure period (SP) corresponding to the clinical manifestations. For one of the patients (patient 9) three seizures associated with ictal asystole were recorded, hence he was treated separately. Results: Group analysis performed on 8 patients (41 seizures) showed that RRi remained unchanged during the preSP, while a significant tachycardia was observed in the SP. A significant increase in the LF component was instead observed during both the preSP and the SP (p<0.001) while HF component decreased only in the SP (p<0.001). For patient 9 during the preSP and in the first part of SP a significant tachycardia was observed associated with an increased sympathetic activity (increased LF absolute values and LF%). In the second part of the SP a progressive decrease in HR that gradually exceeded basal values occurred before IA. Bradycardia was associated with an increase in parasympathetic activity (increased HF absolute values and HF%) contrasted by a further increase in LF until the occurrence of IA. Conclusions: These data suggest that changes in autonomic balance toward a sympathetic prevalence always preceded clinical seizure onset in NFLE, even when HR changes were not yet evident, confirming that wavelet analysis is a sensitive technique to detect sudden variations of autonomic balance occurring during transient phenomena. Finally we demonstrated that epileptic asystole is associated with a parasympathetic hypertonus counteracted by a marked sympathetic activation.

Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy (NFLE).

Nocturnal Frontal Lobe Epilepsy (NFLE) is characterized by onset during infancy or childhood with persistence in adulthood, family history of similar nocturnal episodes simulating non-REM parasomnias (sleep terrors or sleepwalking), general absence of morphological substrates, often by normal interictal electroencephalographical recordings (EEGs) during wakefulness. A family history of epilepsy may be present with Mendelian autosomal dominant inheritance has been described in some families. Recent studies indicate the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the molecular mechanisms of NFLE. Mutations in the genes encoding for the α4 (CHRNA4) and ß2 (CHRNB2) subunits of the nAChR induce changes in the biophysical properties of nAChR, resulting generally in a “gain of function”. Preclinical studies report that activation of a nuclear receptor called type peroxisome proliferator-activated receptor (PPAR-α) by endogenous molecules or by medications (e.g. fenofibrate) reduces the activity of the nAChR and, therefore, may decrease the frequency of seizures. Thus, we hypothesize that negative modulation of nAChRs might represent a therapeutic strategy to be explored for pharmacological treatment of this form of epilepsy, which only partially responds to conventional antiepileptic drugs. In fact, carbamazepine, the current medication for NFLE, abolishes the seizures only in one third of the patients. The aim of the project is: 1)_to verify the clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant NFLE and ADNFLE patients; focousing on the analysis of the polysomnographic action of the PPAR- agonist (fenofibrate). 2)_to demonstrate the subtended mechanism of efficacy by means of electrophysiological and behavioral experiments in an animal model of the disease: particularly, transgenic mice carrying the mutation in the nAChR 4 subunit (Chrna4S252F) homologous to that found in the humans. Given that a PPAR-α agonist, FENOFIBRATE, already clinically utilized for lipid metabolism disorders, provides a promising therapeutic avenue in the treatment of NFLE\ADNFLE.

Graph-based analysis of brain resting-state fMRI data in nocturnal frontal lobe epileptic patients

Il lavoro che ho sviluppato presso l'unità di RM funzionale del Policlinico S.Orsola-Malpighi, DIBINEM, è incentrato sull'analisi dati di resting state - functional Magnetic Resonance Imaging (rs-fMRI) mediante l'utilizzo della graph theory, con lo scopo di valutare eventuali differenze in termini di connettività cerebrale funzionale tra un campione di pazienti affetti da Nocturnal Frontal Lobe Epilepsy (NFLE) ed uno di controlli sani. L'epilessia frontale notturna è una peculiare forma di epilessia caratterizzata da crisi che si verificano quasi esclusivamente durante il sonno notturno. Queste sono contraddistinte da comportamenti motori, prevalentemente distonici, spesso complessi, e talora a semiologia bizzarra. L'fMRI è una metodica di neuroimaging avanzata che permette di misurare indirettamente l'attività neuronale. Tutti i soggetti sono stati studiati in condizioni di resting-state, ossia di veglia rilassata. In particolare mi sono occupato di analizzare i dati fMRI con un approccio innovativo in campo clinico-neurologico, rappresentato dalla graph theory. I grafi sono definiti come strutture matematiche costituite da nodi e links, che trovano applicazione in molti campi di studio per la modellizzazione di strutture di diverso tipo. La costruzione di un grafo cerebrale per ogni partecipante allo studio ha rappresentato la parte centrale di questo lavoro. L'obiettivo è stato quello di definire le connessioni funzionali tra le diverse aree del cervello mediante l'utilizzo di un network. Il processo di modellizzazione ha permesso di valutare i grafi neurali mediante il calcolo di parametri topologici che ne caratterizzano struttura ed organizzazione. Le misure calcolate in questa analisi preliminare non hanno evidenziato differenze nelle proprietà globali tra i grafi dei pazienti e quelli dei controlli. Alterazioni locali sono state invece riscontrate nei pazienti, rispetto ai controlli, in aree della sostanza grigia profonda, del sistema limbico e delle regioni frontali, le quali rientrano tra quelle ipotizzate essere coinvolte nella fisiopatologia di questa peculiare forma di epilessia.