Cognitive impairment and drug responsiveness in mesial temporal lobe epilepsy.

OBJECTIVES: Mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsies. Seizures of MTLE with hippocampal sclerosis (MTLE-HS) are typically resistant to antiepileptic drug (AED) therapy. Although memory disturbances in patients with MTLE-HS are expected, verbal attention and frontal lobe functions may also be impaired. We aimed to examine the relationship between the clinical features and cognitive functions of patients by comparing cognitive test scores of patients with MTLE with few seizures (drug-responsive group) and those with frequent seizures (pharmacoresistant group). METHODS: Seventy-nine patients with MTLE-HS and 30 healthy controls were enrolled. Thirty-four patients were accepted as the drug-responsive group (DrG), and 45 patients were included in the pharmacoresistant group (PRG). Tests evaluating attention, memory, and executive functions were performed on all participants. RESULTS: Forty-nine (62%) female and 30 (38%) male patients with MTLE-HS, and 14 (46.7%) female and 16 (53.3%) male controls participated in the study. The mean age of the patients and controls was 33.53 ±â€¯9.60 (range, 18-57) years and 35.90 ±â€¯7.98 (range, 18-56) years, respectively. Both the DrG and PRG showed poorer performances in tests evaluating memory and frontal lobe functions when compared with the control group (CG). Additionally, attention test results were significantly worse in the PRG than in the DrG. CONCLUSION: It is reasonable to say that increased seizure frequency is the main causative factor of verbal attention deficit due to the poorer attention test results in the PRG. Poor performances in memory and frontal lobe function tests of all patients with MTLE-HS emphasized the importance of the mutual connection between the temporal lobe and prefrontal cortices.

A Qualitative Approach to Health Related Quality-of-Life in Congenital Muscular Dystrophy.

Congenital muscular dystrophies (CMD) cause progressive muscle weakness resulting in severe motor disabilities. Previous studies focused on the effects of motor disability. Here, we explore other factors affecting health related quality-of-life (HRQOL) in CMD. Qualitative interviews were conducted with participant-parent dyads to identify symptoms having the greatest impact on HRQOL. Symptoms were classified into themes and domains representing physical, mental, social health, and disease specific issues. Social role limitations and specific activity impairment were frequently mentioned. A greater understanding of symptoms impacting HRQOL will provide a framework for improved clinical care and patient centered outcomes as new therapies are developed.

Importance of neuropsychological and clinical features to predict seizure control in medically treated patients with mesial temporal epilepsy and hippocampal sclerosis.

OBJECTIVE: It is not yet understood why seizures in certain patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) develop resistance to antiepileptic drugs (AEDs) while others achieve good seizure control with this treatment. We analyzed clinical and neuropsychological features associated with seizure control in patients with MTLE-HS who had not undergone resective surgery. METHODS: We enrolled 40 patients with medically treated MTLE-HS and retrospectively collected the following data from prospective databases: sex, febrile seizures, central nervous system infection, history of head trauma, cognitive impairment, psychiatric disturbances, history of status epilepticus, age at onset of epilepsy, aura, seizure type and frequency, electroencephalography abnormalities, HS side, AEDs, global cognitive status, and neuropsychological functions such as cognitive processing speed, attention and executive functions, verbal and visual memory, language, and visuospatial ability. These factors were compared between patients who achieved seizure control (no seizures or a >50% reduction in seizure frequency) with AED treatment and those who continued with poor seizure control (increase or no change in frequency or <50% reduction) after starting treatment. RESULTS: The factors associated with poor seizure control in the multivariate analysis were >2seizures per month before treatment (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.2-4.8, p=0.04), moderate or severe cognitive impairment (OR 2.1, 95% CI 1.8-7.6, p=0.02), and impairment of >2 neuropsychological functions (OR 2.88, 95% CI 2-6.6, p=0.04). No associations were observed between poor seizure control and specific neuropsychological function impairment. CONCLUSIONS: Poor seizure control in MTLE-HS is associated with moderate-severe cognitive impairment but not with a specific profile of impairment. Recognizing poor prognostic features such as a high frequency of monthly seizures prior to starting AED treatment could help to identify patients with medically intractable MTLE-HS who may be good candidates for early epilepsy surgery.

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.

Differences in visual naming performance between patients with temporal lobe epilepsy associated with temporopolar lesions versus hippocampal sclerosis.

OBJECTIVE: Naming difficulties are frequently observed in patients with temporal lobe epilepsy (TLE). Although damage/removal of regions of the anterior temporal neocortex including the temporal pole is considered critical for those difficulties, 1 relevant hypothesis proposes that hippocampal damage also has a role. Our aim was to better understand the specific involvement of temporal pole and hippocampus in visual object naming. METHOD: We assessed 2 types of patients with TLE on a visual confrontation-naming task: patients with hippocampal sclerosis (HS; n = 16) and patients with a lesion on the tip of the temporal pole that spared the hippocampus entirely (n = 18). A common battery of verbal and nonverbal semantic tasks was administered and used as a semantic memory background. Control group were 20 matched healthy participants. RESULTS: Patients with lesions on their temporal poles differed from patients with HS and control group on naming ability, proportion and rate of error type, and influence of concept familiarity. Of note, naming performance was not affected by hippocampal damage. Using a Bayesian model averaging approach, we found that the number of omission errors distinguished patients with temporal pole damage from patients with HS and controls. This differential pattern occurred despite similar impairment on the semantic memory background in both clinical groups. CONCLUSION: Current findings provide evidence that temporal pole damage produces or contributes to naming impairment in TLE, while also suggesting that the hippocampus is not critical for naming. They also highlight the importance of error-type analysis when evaluating visual naming in TLE. (PsycINFO Database Record

Adhesio interthalamica and cavum septum pellucidum in mesial temporal lobe epilepsy.

The absence of the adhesio interthalamica (AI; also called interthalamic adhesion or massa intermedia) and the presence of a large cavum septum pellucidum (CSP) later in life have been related to neurodevelopmental alterations and have not been systematically investigated in epilepsy to date. This study carried out a MRI evaluation of the AI and CSP in a large sample with mesial temporal lobe epilepsy (MTLE). A total of 179 patients, classified according to the side of the epileptogenic focus, and 156 age- and sex-balanced healthy controls were assessed. Between-group comparisons of the prevalence and length of both AI and CSP were conducted. Neuropsychological assessments were also performed in 160 MTLE patients. The patients exhibited reduction in the AI prevalence (P < 0.05; FDR-uncorrected) and length (P < 0.05; FDR-corrected) when compared to controls. Patients without AI showed lower scores in a proportion of neuropsychological tests than patients with AI. No CSP differences were found between MTLE patients and controls. These results support that AI anomalies have clinical significance in MTLE, as well as indicate that neurodevelopmental alterations may be implicated in this disorder.

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. METHODS: We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. RESULTS: TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. CONCLUSIONS: Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up.

Update on Hippocampal Sclerosis.

The diagnostic hallmarks of hippocampal sclerosis (HS) are severe volume loss of the hippocampus, severe neuronal loss, and reactive gliosis involving primarily two especially vulnerable fields, CA1 and the subiculum. Occasionally, HS may be the only neuropathological change detected in older individuals with dementia and is known as pure HS. In the majority of cases, HS occurs in the setting of other degenerative changes, usually Alzheimer's disease (AD). In these cases, it is classified as combined HS. Although a clinical profile for HS has been identified, its similarities with AD make the diagnosis during life quite challenging; thus, the diagnosis is often made postmortem. The pathogenesis of HS is not completely understood, but the strong association with transactive response DNA-binding protein 43 (TDP-43), in approximately 90%, and the recent discovery of genetic risk factors are important contributions to a better understanding of the disease process.

Religiosity aspects in patients with epilepsy.

The objectives of this study were to assess religiosity aspects in patients with epilepsy (PWEs) and controls and to determine whether such aspects were related to the samples' clinical, sociodemographic, and QOL-31 data. The Duke Religion Index was administered to 159 adult PWEs and 50 controls. The relationships between the Duke Religion Index and the study variables of the two groups were compared. Intrinsic religiosity (IR) and nonorganizational religiosity (NOR) were higher in PWEs than in controls. Logistic regression showed that being female (p=0.022) and having mesial temporal lobe epilepsy with hippocampus sclerosis (MTLE-HS) (p=0.003) were predictors of high organizational religiosity (OR) and that high NOR was associated with MTLE-HS (p=0.026) and controlled seizures. Further, only MTLE-HS (p=0.002) was predictive of high IR. The Duke Religion Index and QOLIE-31 scores were not related. Different forms of interictal religiosity are related to clinical aspects of epilepsy.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently.

Spirituality aspects in patients with epilepsy.

PURPOSE: Do epilepsy and spirituality interact? This study aimed to determine whether an easy-to-administer scale, such as the spirituality self-rating scale (SSRS), could detect increased religiousness in people with epilepsy and verify how epilepsy influences spirituality. METHODS: A total of 196 consecutive patients with epilepsy (epilepsy group, EG) with a mean age and standard deviation of 46.5 ± 14.8 years and 66 subjects with no history of neurological or other chronic disorders (control group, CG) were assessed by the SSRS and neurologically. RESULTS: The SSRS scores of the EG and CG did not differ significantly (22.8 ± 5.1 and 22.0 ± 5.7, respectively). Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) had significantly higher SSRS scores than those with other epileptic syndromes and, than in individuals of the CG. Multiple regression showed that the factors significantly associated with greater spirituality (greater SSRS score) for the EG, were lower education level, abnormal background EEG activity, and MTLE-HS. Other relationships with the clinical features of epilepsy and with the presence of psychiatric co-morbidity were not found. CONCLUSION: The present findings do not confirm a specific role of epilepsy in spirituality or of "epileptic hyperreligiosity," but suggest that spirituality in people with epilepsy is influenced by education level, and may also stem from epilepsy-related factors such as abnormal background EEG activity and the presence of MTLE-HS.

Sexual desire and satisfaction after resective surgery in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Utilizing a questionnaire, we inquired about the self-perceived sexual behavior of 50 married males with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL) and compared the results with those of 50 age-matched healthy married males. The sexual desire and satisfaction of the patients were poor when compared to the controls. Although a majority of the sexual domains improved following ATL, even after a median duration of five years, the sexual status of the patients did not match with that of the controls. Those who, after ATL, were seizure free, had one or no antiepileptic drug (AED) and had an EEG without epileptiform abnormalities achieved a better sexual outcome. We conclude that sexual dysfunction is frequent in male patients with MTLE-HS. They require preoperative assessment to identify their sexual inadequacies as well as counseling about the expected post-ATL sexual outcome. Discontinuation of enzyme-inducing AEDs facilitates post-ATL improvement in sexual function.

Blurring in patients with temporal lobe epilepsy: clinical, high-field imaging and ultrastructural study.

Magnetic resonance imaging-positive temporal lobe atrophy with temporo-polar grey/white matter abnormalities (usually called 'blurring') has been frequently reported in patients with temporal lobe epilepsy associated with hippocampal sclerosis. The poor distinction of grey and white matter has been attributed to various causes, including developmental cortical abnormalities, gliosis, myelin alterations, a non-specific increase in temporal lobe water content and metabolic/perfusion alterations. However, there is still no consensus regarding the genesis of these abnormalities and no histopathological proof for a structural nature of magnetic resonance imaging changes. The aim of this study was to investigate the pathological substrate of temporo-polar blurring using different methodological approaches and evaluate the possible clinical significance of the abnormalities. The study involved 32 consecutive patients with medically intractable temporal lobe epilepsy and hippocampal sclerosis who underwent surgery after a comprehensive electroclinical and imaging evaluation. They were divided into two groups on the basis of the presence/absence of temporo-polar blurring. Surgical specimens were examined neuropathologically, and selected samples from both groups underwent high-field 7 T magnetic resonance imaging and ultrastructural studies. At the clinical level, the two groups were significantly different in terms of age at epilepsy onset (earlier in the patients with blurring) and epilepsy duration (longer in the patients with blurring). Blurring was also associated with lower neuropsychological test scores, with a significant relationship to abstract reasoning. On 7 T magnetic resonance image examination, the borders between the grey and white matter were clear in all of the samples, but only those with blurring showed a dishomogeneous signal in the white matter, with patchy areas of hyperintensity mainly in the depth of the white matter. Sections from the patients with blurring that were processed for myelin staining revealed dishomogeneous staining of the white matter, which was confirmed by analyses of the corresponding semi-thin sections. Ultrastructural examinations revealed the presence of axonal degeneration and a significant reduction in the number of axons in the patients with blurring; there were no vascular alterations in either group. These data obtained using different methodological approaches provide robust evidence that temporo-polar blurring is caused by the degeneration of fibre bundles and suggest slowly evolving chronic degeneration with the redistribution of the remaining fibres. The article also discusses the correlations between the morphological findings and clinical data.

Validity and reliability of the Portuguese version of the quality of life in epilepsy inventory (QOLIE-31) for Brazil.

PURPOSE: We report the cultural adaptation and psychometric properties of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) for the Portuguese language and Brazilian culture. METHODS: This study involved 150 outpatients: 50 presurgical patients with refractory temporal lobe epilepsy (TLE) related to mesial temporal sclerosis (MTS), 50 patients with juvenile myoclonic epilepsy (JME), and 50 seizure-free patients with TLE. They completed the QOLIE-31, Nottingham Health Profile (NHP), Beck Depression Inventory (BDI), and Adverse Events Profile (AEP) and underwent a neuropsychological evaluation (NE). Internal consistency reliability, interrater and test-retest reliability, and construct validity were assessed. RESULTS: QOLIE-31 mean scores were 33.1 (Social Function), 68.9 (Overall Quality of Life), 56.5 (Seizure Worry), 64.1 (Emotional Well-Being), 63.7 (Energy/Fatigue), 38.9 (Cognitive Function), and 49.7 (Medication Effects). Internal consistency was high (Cronbach's alpha), as were the associations between QOLIE-31 and the BDI, NHP, AEP, and NE. CONCLUSION: The Portuguese/Brazilian version of the QOLIE-31 inventory showed good reliability, validity, and construct validity.

Clinical holistic medicine: chronic infections and autoimmune diseases.

The consciousness-based (holistic) medical toolbox might be useful in general practice and in cases of recurrent infections and chronic infection or inflammation. From our clinical experiences, there is hope for improvement from a number of diseases caused by disorders affecting the regulation of the immune system when the physician includes the holistic medical approach. Our scientific understanding of the connection between consciousness and cellular order is still limited. Consciousness-based holistic medicine removes (as explained by the holistic process theory of healing) the "blockages" in the tissues of the body and facilitates function and informational exchange of the cells of the body. Many blockages and repressed feelings in an area would imply "noise and disturbances" on the level of intercellular communications, which in turn means major difficulties for the cells of the immune system. For this they are totally dependent on the body information system, which the holistic treatment aims to recover. Processing the blockages increases the coherence of the cells and organism, thus increasing the intercellular flow of information in the area and thus strengthening the immune defense and healing the disease. The area of clinical holistic medicine is going through a rapid development and the toolbox of consciousness-based medicine is available for dealing with many diseases arising from disturbances in the regulation of the immune system. Holistic medicine has yet to be better explained scientifically and our proposed holistic cures have yet to be documented clinically. We invite the medical community to cooperate on this important challenge.

Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis.

Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.

Cognitive consequences of coexisting temporal lobe developmental malformations and hippocampal sclerosis.

OBJECTIVE: To characterize patterns of cognitive functioning in a well-defined group of patients with MRI-identified coexisting left temporal lobe developmental malformations (TLDM) and mesial temporal sclerosis (MTS), and to examine neuropsychological outcome in this dual-pathology group following epilepsy surgery. METHODS: Cognitive functioning in patients with left TLDM and MTS (n = 15) was compared with patients with isolated left MTS (n = 40). TLDM and MTS were identified by high-quality MRI protocol. Patients were administered a battery of neuropsychology tests as part of their presurgical workup for possible epilepsy surgery. Unilateral temporal lobe resection was performed on 10 of the dual-pathology patients and 34 of the isolated MTS patients. Postoperative cognitive performance was also assessed. RESULTS: Both groups displayed impairments in verbal and visual memory, language, and academic achievement. Performance on measures of psychometric intelligence, executive function, and attention were not impaired and were similar between groups. Presence of dual pathology was associated with a significantly less efficient verbal encoding strategy on the word list learning task. Postoperatively, declines were noted for both groups across tasks of verbal memory and language. Groups were not different significantly in terms of neuropsychological outcome after surgery. CONCLUSION: Patients with coexisting TLDM and MTS have impaired cognitive functioning similar to MTS patients-in particular, with regard to episodic memory and language deficits. Temporal lobe resection produces similar cognitive changes in both groups.