Dissertations / Theses on the topic 'Nocturnal Frontal Lobe Epilepsy'

Idiopathic epilepsies are common and devastating neurological disorders in which genetic background and physiopathological mechanisms underlying the clinical phenotype are not fully characterized yet. These diseases are assumed to have a strong genetic component, being monogenic or oligo/polygenic with different recurrence risks in the same family. However, even in monogenic epilepsy, additional genes and environmental factors may modulate its expression, thus resulting in incomplete penetrance and variable phenotype. Ethiology, phenotypic manifestations and prognosis are indeed highly heterogeneous. Idiopathic epilepsies represent about 30-40% of all epilepsies in childhood and 20% in adults. Most of them are complex diseases: patients may shift from one phenotype to another during their lifetime and parents affected by one form may have children suffering from another epileptic syndrome. The identification of genes responsible for distinct epilepsy syndromes or influencing the risk for epilepsy has important implications, for both research and clinical purposes. In this work we studied the genetic bases of two different epilepsies: nocturnal frontal lobe epilepsy (NFLE/ADNFLE) and febrile seizures (FS/GEFS+). In the case of the NFLE/ADNFLE phenotype, we performed a mutational screening of known genes, including CRH and its promoter, in a sample of both sporadic and familial patients. The study allowed the identification of: an already known mutation in the CHRNA4 gene (p.Ser284Leu) originated de novo in one NFLE patient; three unknown variants in the CRH promoter in both sporadic and familial patients which we demonstrated to not cosegregate with the disease; one unknown missense mutation in the coding portion of the CRH gene in one ADNFLE patient. By functional in vitro analysis we demonstrated that the missense mutation causes impairment in the production and release of the CRH hormone. This impairment could be related to an altered capability of patients to respond quickly to stress agents. Finally, by analyzing candidate genes encoding the orexin system we demonstrated an unlikely role of this system in the pathogenesis of ADNFLE: none of the patients has mutations in the three genes. In the study of FS/GEFS+ phenotype, the role of the SCN1A gene was evaluated. Several intronic and exonic polymorphisms were detected. In the case of unknown intronic variants, an in silico analysis revealed that these variations do not introduce or remove any splicing sites. Interestingly, we found in a patient two missense mutations. These two variants co-segregated with the pathology being present in all affected individuals and in two obligate carriers. Owing to the location of both mutations in important regions of the sodium channel, we are now testing the hypothesis of their causative role in the pathogenesis of this family’s disease. The study will allow the evaluation of the effect of these mutations (considered either singly or in conjunction with the other) on the activation/inactivation properties of the sodium channel in the presence/absence of the β-1 accessory subunit.

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.

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.

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.

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.

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.

A close relationship exists between sleep and epilepsy. While many forms of epilepsy may be influenced by the sleep-wake cycle, this phenomenon is particularly evident in frontal lobe epilepsy where affected individuals may experience seizures exclusively during sleep (nocturnal frontal lobe epilepsy, NFLE). In this thesis, three aspects of the relationship between sleep and frontal lobe epilepsy are examined. Firstly, serotonergic neurotransmission across the human sleep-wake cycle was studied using the novel PET ligand l8F-MPPF, a serotonergic 5HT)A receptor radioligand sensitive to endogenous serotonin release. Fourteen individuals with narcolepsy underwent 18F-MPPF PET scans during sleep and wakefulness. The study demonstrated a 13% increase in 18F-MPPF binding potential (p < 0.01) during sleep, indicating a reduction in serotoninergic neurotransmission, in line with existing animal data. Secondly, the characterisation of benign, non-epileptic parasomnias and their distinction from nocturnal frontal lobe seizures was addressed in two studies. The first comprised an analysis of the historical features of these conditions, and included the development and validation of a clinical scale for the diagnosis of nocturnal events. The second comprised a detailed semiological analysis of a series of parasomnias recorded on video-EEG monitoring, and a statistical comparison with seizures in NFLE. Although similarities between NFLE and parasomnias were observed, the results provide an evidence base for the confident distinction of these disorders. Finally, the familial form of NFLE (autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE) is associated with mutations in genes for nicotinic acetylcholine receptor subunits, but recognised mutations account for only a minority of reported cases. The last study presented here is a clinical and genetic analysis of two large families with an unusually severe ADNFLE phenotype. Affected individuals had refractory epilepsy and increased rates of mental retardation and psychiatric disorders and, in one family, linkage studies suggest a previously unrecognised underlying mechanism.

La epilepsia del lóbulo frontal es la segunda más frecuente en la mayoría de las series publicadas, después de la epilepsia temporal. Sus características clínicas y electroencefalográficas son muy variadas, lo que hace de su diagnóstico y tratamiento un reto en la práctica clínica. Las crisis frontales suelen aparecen en “clusters”, con frecuencia generalizan y el aspecto electroencefalográfico de la actividad intercrítica y crítica suele ser difícil de interpretar por la gran difusión que suele acompañar a la actividad paroxística en este tipo de epilepsia. En este trabajo se han estudiado 175 casos con alteraciones intercríticas en el electroencefalograma, realizando un análisis exhaustivo de todos sus aspectos morfológicos. Se ha dividido la muestra en función de tres aspectos morfológicos para estudiar la actividad intercrítica: Su morfología (puntas; ondas agudas simples; ondas agudas difásicas; polipuntas; ondas lentas irregulares), su voltaje (menor de 50 μV, entre 50-100 μV, 100-20 0μV y más de 200 μV) y la actividad que sigue a ésta actividad paroxística. Las ondas agudas tanto simple como difásicas de 50-200 μV fueron el grupo más frecuente en la morfología intercrítica. A continuación, mucho menos frecuentes, las puntas, especialmente de menos de 50 μV. En cuanto a la actividad crítica se han estudiado en detalle sus características morfológicas al inicio de la crisis y sus frecuencias, con el propósito de disponer de una clasificación útil desde el punto de vista electroencefalográfico en el estudio de este tipo de crisis. Morfológicamente el ritmo reclutante fue la característica morfológica más frecuentemente observada al inicio de las crisis, seguida de un ritmo reclutante de baja amplitud. Las crisis registradas fueron cortas, frecuentemente de segundos de duración, comenzando con un ritmo reclutante de 15 Hz de frecuencia media y progresivo enlentecimiento desde el inicio. El enlentecimiento frontal observado en el postcrítico ayudó a localizar el foco. Algunos presentaron clusters de varias crisis en el mismo registro y los cambios en la poligrafía respiratoria y ECG fueron frecuentes durante las crisis frontales registradas. Encontramos que la localización del foco predice la localización del inicio crítico y que el patrón crítico desde un punto morfológico se mantiene a lo largo del tiempo para cada paciente. Una parte fundamental del trabajo se encuentra en el anexo incluido a modo de “atlas”, en el que se exponen alguno de los casos objeto de estudio, detallando observaciones electroencefalográficas de interés.
Frontal lobe epilepsy (FLE) is the second most common type of epilepsy after temporal lobe one. Clinical and electroencephalographic (EEG) features are also very varied, being its diagnose usually a challenge in clinical practice. Frontal lobe seizures appear frequently in cluster, with secondary generalization, and its EEG appearance is usually difficult to determine, due to the widespread the interictal and ictal activity usually achieves. This is an electroencephalographic study, where 175 cases with frontal lobe EEG interictal epileptiform activity have been carefully studied regarding an electroencephalographic point of view, with special emphasis in the morphology of the waveforms. We have divided the sample regarding three different aspect for studying the interictal activity: Its morphology (spike; simple sharp wave; diphasic sharp waves; poly-spikes; irregular slow waves) its voltage (less than 50 μV, 50-100 μV, 100-200 μV and more than 200 μV) and the activity that follows the waveform. The main interictal waveform in our sample was the sharp wave group, both simple and diphasic between 50 to up to 200 μV. Afterwards, much less frequently, the spikes, specially of less than 50 μV. Regarding the ictal activity, some morphologic details at onset are studied with the aim to make available a practical EEG classification for these seizures. Morphologically the synchronized rhythm was the most frequent morphology observed at seizure onset, followed by a low amplitude synchronized rhythm. –recorded seizures were short, frequently of seconds of duration, and they started with a synchronized rhythm of 15 Hz mean frequency, with a progressive slowing after onset. Postictal frontal slowing activity was meaningful, adding value information for locating the focal epileptiform activity. Some patients presented clusters of several seizures within the same recording and changes in breathing polygraphy and EKG were very common during the frontal lobe recorded seizures. We found that the focus location predicts the location of seizure onset, and that the seizure pattern from a morphological point of view remains the same for each patient along time. A major point of interest of this work is included in the graphical appendix, where some interesting EEG features are detailed.

Gracias al desarrollo de las técnicas de neuroimagen en las últimas décadas se han conseguido avances importantes en el conocimiento de la epilepsia y sus mecanismos; descubriéndose cuestiones calves que han modificado conceptos clásicos y generado nuevas hipótesis en este campo. En los trabajos que componen esta tesis doctoral se utiliza como herramienta común la resonancia magnética para investigar varios aspectos que comprenden desde la función cognitiva a aspectos estructurales. En concreto se han empleado técnicas de resonancia magnética funcional y análisis cuantitativo de imagen estructural para responder a las hipótesis planteadas en los distintos trabajos que la conforman. La tesis comprende tres estudios: los dos primeros se centran en la epilepsia frontal y el tercero en mapeo de lenguaje pacientes bilingües con epilepsia. La epilepsia frontal (EF) es el segundo síndrome más prevalente dentro de las epilepsias focales, después de la epilepsia temporal. Sin embargo, debido a su complejidad como grupo, existen pocos estudios concluyentes a cerca de la función cognitiva en estos pacientes. Tampoco se conocen los cambios funcionales en las redes cognitivas que subyacen los déficits cognitivos en este grupo. Comprender estos aspectos contribuiría de manera importante a entender los déficits cognitivos en este grupo así como a comprender las alteraciones causadas por la cirugía. El primer trabajo de esta tesis estudia la memoria a largo plazo en pacientes con EF. Existen datos contradictorios sobre los déficits de memoria en pacientes con EF. Esta función ha sido poco explorada a pesar de la prevalencia de problemas de memoria en este grupo. Utilizando un paradigma de memoria en resonancia magnética funcional se caracterizaron los cambios funcionales secundarios a la epilepsia frontal y las alteraciones que se asocian al deterioro de esta función. En el segundo trabajo sobre epilepsia frontal se explora la presencia de cambios estructurales en sustancia gris en pacientes con EF. A diferencia de los pacientes con epilepsia temporal, en este grupo no existen estudios que exploren de manera cuantitativa cambios comunes en la estructura de la sustancia gris. Para ello se han empleado técnicas cuantitativa voxel por voxel que son altamente sensibles a cambios no identificables con inspección visual. La resonancia funcional (RMf) de lenguaje se ha integrado como parte importante de los estudios pre quirúrgicos en epilepsia. Esta necesidad se ve justificada por la alta incidencia de lateralización atípica del lenguaje en este grupo de pacientes. Este test se ha validado clínicamente en su mayoría utilizando la lengua nativa de los sujetos. Cuando el test se realiza en una segunda lengua como es el caso de población inmigrante se plantea la cuestión de la validez del test. Aunque existen un gran número de estudios de bilingüismo utilizando RMf, estos se han centrado en la búsqueda de diferencias en redes neuronales de las diferentes lenguas y no en el análisis de la validez clínica de estos mapas. En el tercer trabajo de la tesis se investiga las diferencias en los mapas de lenguajes obtenidos con RMf cuando se utiliza la lengua materna y cuando se utiliza una lengua secundaria. Con este estudio pretendemos evaluar la validez clínica de realizar mapeo de lenguaje con resonancia en una lengua secundaria.
Imaging techniques have led to the discovery of key questions in the field of epileptology. In this thesis, functional and structural aspects of focal epilepsies are investigated through magnetic resonance imaging (MRI). In particular, functional MRI and voxel wise analysis are used as the tool to test the hypothesis posed in the different studies that conform this thesis. The thesis is divided into three studies; two of them focus on frontal lobe epilepsy and the third one on language mapping of bilingual patients with epilepsy. Frontal lobe epilepsy is the second most prevalent syndrome among the focal epilepsies after temporal lobe epilepsy. However, it has proved challenging to characterize cognitive dysfunction within this group. Furthermore, the functional anatomy correlates of dysfunction in FLE is still unknown. Understanding these changes may help to characterize better the cognitive profile of this group. It may also improve the understanding of the changes in cognitive function as the result of surgery. In particular one of the studies focuses in memory function in patients with FLE. This cognitive aspect has received little attention in this group of patients. However, there is a significant prevalence of memory deficits in patients with Frontal lobe epilepsy. Using functional MRI (fMRI) I investigated long term memory in patients with FLE in order to characterize the functional anatomy that underlies memory dysfunction in this group of patients. The second study on FLE explores the structural changes in this syndrome. It uses voxel wise quantitative MRI techniques to identify common structural changes across this heterogeneous group. Language fMRI is widely used as part of the pre-surgical investigations of patients with drug resistant epilepsy. This is justified given the high prevalence of atypical language dominance in patients with epilepsy. The clinical validation of these tests have been performed using the subject’s native language. However this is a problem when the evaluated subject has to perform the test in a secondary language as it is the case of immigrant population. Although there is a large number of fMRI studies in bilingualism, these mainly focus in the differences in language networks between the different languages in bilinguals. The third study in this thesis investigates the differences in the language networks that support native and learned languages in bilingual patients with epilepsy and asses the clinical validity of mapping language using language paradigms in a subject’s first and second languages.

A lobectomia frontal é um procedimento neurocirúrgico frequentemente realizado para o tratamento de tumores cerebrais, epilepsia refratária, e outras patologias que requerem remoção extensa do lobo frontal. Embora seja um procedimento relativamente comum, foram encontrados apenas alguns relatos na literatura acerca da técnica cirúrgica, com pouca consideração acerca da anatomia relevante para esse procedimento. OBJETIVOS: O principal objetivo desta tese é apresentar parâmetros anatômicos e considerações técnicas para a remoção da substância cinzenta do lobo frontal (decorticação do lobo frontal) como uma alternativa a lobectomia frontal. A finalidade deste estudo é a maximização da remoção cerebral, diminuindo a perda sanguínea, e evitando a abertura do corno frontal do ventrículo lateral. MATERIAIS E MÉTODOS: O estudo anatômico foi realizado em 15 cabeças cadavéricas adultas. Os dados clínicos foram baseados em 15 decorticações frontais realizadas de 2002 a 2014. RESULTADOS: A decorticação frontal envolve as superfícies lateral, medial e basal, e consiste em 5 passos principais: a) coagulação e secção dos ramos arteriais da superfície lateral do lobo frontal; b) ressecção subpial paramediana do lobo frontal até a localização do joelho do corpo caloso; c) ressecção da substância cinzenta da superfície lateral do lobo frontal sem entrar no corno frontal; d) identificação e preservação do trato olfatório; e) remoção da substância cinzenta da superfície basal do lobo frontal. Esta técnica cirúrgica foi aplicada em 15 casos, em nenhum deles o corno frontal do ventrículo lateral foi aberto, evitando complicações da abertura do mesmo. CONCLUSÃO: A decorticação frontal guiada por parâmetros anatômicos pode ser uma das técnicas cirúrgicas a ser considerada quando há necessidade da ressecação extensa do lobo frontal (especialmente substância cinzenta). A técnica proporciona máxima remoção do lobo frontal, preservação do corno frontal e da área motora suplementar, e redução da perda sanguínea
BACKGROUND: The frontal lobectomy is a frequently performed neurosurgical procedure for treating brain tumors, refractory epilepsy, and other disorders that require extensive removal of the frontal lobe. In spite of being a relatively common procedure, there are only few reports available regarding its surgical technique and little attention has been given to the anatomy relevant to this procedure. OBJECTIVES: The authors present the anatomical landmarks and technical nuances for removing the gray matter of the frontal lobe (frontal lobe decortication) as an alternative to frontal lobectomy. The goals are to maximize the brain removal, minimize the blood loss, and avoid opening the frontal horn of the lateral ventricle. MATERIAL AND METHODS: The anatomical study was performed in 15 adult cadaveric heads. The clinical data are based on 15 frontal resections performed from 2002 to 2014. RESULT: The frontal decortication involves the lateral, medial, and basal surfaces of the frontal lobe, and it consists of 5 main steps: a) coagulation and section of the arterial branches of the lateral surface of the frontal lobe; b) paramedian subpial resection of the frontal lobe until the genu of the corpus callosum is located; c) resection of the gray matter of the lateral surface of the frontal lobe without entering the frontal horn; d) identification and preservation of the olfactory tract; e) removal of the gray matter of the basal surface of the frontal lobe. This surgical technique was applied in 15 cases, and it was possible to preserve the frontal horn in all the patients when following this technique, avoiding complications resulted by its opening. CONCLUSION: The frontal decortication guided by intraoperative anatomical landmarks can be one of the surgical techniques to be considered when an extensive frontal lobe resection (especially gray matter) is needed. It offers maximum frontal lobe removal, preservation of the frontal horn and supplementary motor area, and reduced blood loss

Pacientes com epilepsias farmacorresistentes estão cada vez mais se beneficiando do tratamento cirúrgico, dado o avanço nas técnicas de diagnóstico. Com a cirurgia, busca-se tornar o paciente livre de crises sem que para isso sejam provocados déficits neurológicos secundários. Para que isso seja alcançado é fundamental que a região cerebral epileptogênica seja delimitada com precisão. Os principais meios que o neurofisiologista dispõe para localizar a zona epileptogênica (ZE) na avaliação pré-cirurgica são a eletroencefalografia escapelar e a ressonância magnética (RM). Nos casos em que a RM não apresenta lesões ou os dados obtidos são conflitantes as técnicas de imagem funcional tais como a tomografia por emissão de fóton único (SPECT) e a tomografia por emissão de pósitron passam a ter um papel decisivo. O SPECT crítico apresenta uma imagem da perfusão sanguínea cerebral no momento da crise evidenciando, assim, as áreas cerebrais que estavam mais ativas. A técnica de subtração do SPECT intercrítico do crítico e o corregistro deste resultado coma RM do paciente (SISCOM) tem sido estudada como uma maneira de aumentar a sensibilidade e especificidade do SPECT crítico. Este trabalho buscou estudar e validar o papel dos SPECT crítico, intercrítico e SISCOM na localização da ZE. Todos os pacientes com suspeita de epilepsias refratária do lobo frontal baseada nos outros exames, operados no período de 2007 a 2011 e que realizaram um SPECT crítico e um intercrítico foram considerados nesse estudo. Para cada SPECT crítico foi realizado o SISCOM e o resultado comparado com o local da ressecção e o resultado cirúrgico sendo calculadas as métricas de desempenho diagnóstico de cada um dos métodos de neuroimagem funcional. No total foram operados 14 pacientes e 5 tiveram um bom resultado cirúrgico. O SPECT crítico apresentou 40% de sensibilidade e 88,9% de especificidade enquanto que o SPECT intercrítico apresentou 40% de sensibilidade e 66,7% de especificidade. O SISCOM foi o método com melhores parâmetros de desempenho apresentando uma sensibilidade de 60% e uma especificidade de 88,9%. Esses resultados coadunam com os dados encontrados na literatura em que o SISCOM é o estado da arte na interpretação do SPECT crítico e sugerem que o SISCOM tem potencial para ser utilizado na avaliação pré-cirurgica de pacientes com suspeita de epilepsias do lobo frontal.
The surgical treatment for patients with intractable epilepsies has become more efficient with the evolution of diagnosis techniques. The surgery aims at rendering the patient free of seizures, without postoperative neurological deficits. In order to accomplish this, it is of major importance to precisely delineate the epileptogenic zone (EZ). The main exams the neurologists use in order to find the EZ in the pre-surgical evaluation are the scalp electroencephalography and the magnetic resonance imaging (MRI). However, in cases where the MRI doesn\'t show any lesion or there are conflicting data, functional imaging such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography techniques play a crucial role. Ictal SPECT shows a snapshot of cerebral blood perfusion during the seizure, highlighting the most active areas during the ictus state and it has been shown this technique is useful in localizing the EZ in frontal lobe epilepsy cases. Sensitivity and specificity of ictal SPECT might be improved by a developed Computer Aided Diagnosis tool that subtracts the interictal SPECT image from the ictal one and coregisters the result with the MRI (SISCOM). In the present study, we aimed to evaluate the contribution of SISCOM to the pre-surgical evaluation in frontal lobe epilepsies. We considered for this study patients submitted to frontal lobe epilepsy surgery at our institution between 2007 and 2011 and with at least one ictal and one interictal SPECT. 14 patients were included and only 5 had a good outcome after the surgery. The ictal SPECT had a sensibility of 40% and specificity of 88,9% while the interictal SPECT showed a sensibility of 40% and a specificity of 66,7%. The sensitivity of the SISCOM tool was 60% and the specificity 88,9%.These results agree with the literature showing that SISCOM is the state-of-the-art in interpreting the ictal SPECT and has the potential to be used during presurgical evaluation of patients being considered for surgical treatment of frontal lobe epilepsy.

The Whole thesis is in Afrikaans: Epilepsy is a phenomenon that can manifest in a variety of ways, which differ mainly in severity, appearance, aetiology, effect and control thereof. In this study a lack of knowledge and education about epilepsy is pointed out as a factor that was neglected over the years. It is of utmost importance to distinguish between three main categories of epilepsy as all three types have a restraining effect that may leave any learner vulnerable. The popular belief about the concept epilepsy until recently did not recognize the type of epilepsy where a disturbance in consciousness or relapse in consciousness only occurred as in the case with elementary partial attacks (temporal and frontal lobe epilepsy). Ignorance about temporal and frontal lobe epilepsy, as well as the fact that the physical symptoms of this type of epilepsy are very subtle in nature, may be the cause why acceptance of this condition has been slow or undervalued. In reality learners with lobe epilepsy are not regarded as disabled and should such a learner not be diagnosed and not receive the correct treatment, he/she will not be able to function optimally. The researcher has made a study of epilepsy as well as the physical, cognitive, emotional, social, self image impact on the learner in family and school context. The impact of epilepsy on the primary school learner was studied from a gestalt point of view. In this study the researcher employed both a quantitative and qualitative research approach. It was therefore fitting to formulate a research question and a hypothesis. The research question formulated for this study is as follows: What is the knowledge basis of teachers regarding learners with lobe epilepsy? The empirical study indicated that the researcher could provide an answer to the research question by way of semi-structured interviews that indicated that the knowledge basis of the teachers was not sufficient to identify learners with this phenomena. The researcher determined through these interviews that teachers experienced a need to extend their knowledge about temporal and frontal lobe epilepsy. The hypothesis formulated for this study is as follows: Should information and clear guidelines regarding the identification of a learner with lobe epilepsy be offered to teachers, the learner with lobe epilepsy would be identified timeously in the school system. The researcher did a pre-test on the knowledge levels on lobe epilepsy among teachers by way of questionnaires. The pre-test was followed by a structured information session after which an after-test was done by way of questionnaires to determine the change in the teachers’ knowledge basis. The empirical study showed that the teachers’ knowledge basis increased due to the information session offered to them. After this study the teachers could identify learners and refer them for diagnosis and treatment as a result of an increased knowledge basis about this phenomena. The study was followed up by guidelines offered to the teachers on identifying the primary school learner with temporal and frontal lobe epilepsy.
Thesis (DPhil (Social Work))--University of Pretoria, 2005.
Social Work and Criminology
unrestricted

M.A. (Clinical Psychology)
Attention deficit hyperactivity disorder (ADHD) is a form of psychopathology characterised by difficulties with hyperactivity, attention and behavioural inhibition. Although ADHD has been historically considered a disorder specific to children, the contemporary consensus among researchers is that, in some cases, ADHD may persist into adulthood. Neurologically, ADHD is associated with deficits in the executive functions, located in the frontal lobe. Cortical arousal, which refers to the level of neuronal activity in the cerebral cortex and is measurable using electroencephalograph machinery (EEGs), is usually lower in the frontal lobes in those with ADHD when compared to individuals without the disorder. With regards to anxiety disorders, which are dysfunctional variations in the normal fear response, the aetiology of the pathologies in this category are multifaceted and complex. At the neurological level, however, there is a clear link between anxiety disorders and hypervigilance, which is characterised by high cortical arousal in the frontal lobes. Despite the fact that, at face value, it seems impossible for an increase and decrease in cortical arousal to occur simultaneously, ADHD is often diagnosed alongside anxiety disorders, and it is this anomaly which is the focus of this study. Electroencephalograph machinery (EEGs) are able to measure levels of cortical arousal using electrodes placed on the scalp. This research employs this equipment in order to elucidate on how cortical arousal manifests during a task that demands significant involvement from the frontal areas of the brain. A quasi-xperimental research design using non-parametric statistics (Mann-Whitney U Test) was used in order to compare the levels of cortical arousal between 4 groups of 5 research participants with either ADHD, an anxiety disorder, comorbid ADHD and anxiety and no discernible psychopathology. The significant results found in this study point to the fact that, in cases where ADHD and anxiety disorders occur comorbidly, there is a possibility that the anxiety component enables an individual to achieve more pronounced levels of attention, concentration and focus than normal participants and those with ADHD alone...