RESUMEN

BACKGROUND: Gliosis only (GO) and hippocampal sclerosis (HS) are distinct histopathological entities in mesial temporal lobe epilepsy. This study explores whether this distinction also exists on a functional level when evaluating pre- and postoperative memory. METHODS: Using a retrospective matched case-control study design, we analysed verbal and visual memory performance in 49 patients with GO and 49 patients with HS before and one year after elective surgery. RESULTS: Clinical differences were evident with a later age at seizure onset (18±12 vs 12±9 years) and fewer postoperative seizure-free patients in the GO group (63% vs 82%). Preoperatively, group and individual-level data demonstrated that memory impairments were less frequent, less severe and relatively non-specific in patients with GO compared with HS. Postoperatively, verbal memory declined in both groups, particularly after left-sided resections, with more significant losses in patients with GO. Factoring in floor effects, GO was also associated with more significant visual memory loss, particularly after left resections. CONCLUSIONS: Compared with HS, GO is characterised by (1) a later onset of epilepsy, (2) less pronounced and more non-specific memory impairments before surgery, (3) a less successful surgical outcome and (4) a more significant memory decline after surgery. Overall, our results regarding cognition provide further evidence that GO and HS are distinct clinical entities. Functional integrity of the hippocampus appears higher in GO, as indicated by a better preoperative memory performance and worse memory outcome after surgery. The different risk-benefit ratios should be considered during presurgical patient counselling.

RESUMEN

Introduction: Our goal was to investigate whether biomarkers of cerebral damage are found in autoimmune-mediated epilepsy (AIE) and whether these can differentiate AIE from other seizure disorders. Methods: We retrospectively searched our cerebrospinal fluid (CSF) database for patients with definite AIE, hippocampal sclerosis due to other causes (HS), genetic generalized epilepsy (GGE), and psychogenic, non-epileptic seizures (PNES). We measured serum and CSF tau, neurofilament 1 (NFL), glial fibrillary acid protein (GFAP), and ubiquitin-carboxy-terminal hydrolase L1 with a single-molecule array. Results: We identified suitable samples from patients with AIE (n = 13) with different antibodies and compared them to HS (n = 13), GGE (n = 7), and PNES (n = 8). The NFL levels were significantly elevated in the serum (p = 0.0009) and CSF (p < 0.0019) of AIE patients. The AIE group was significantly older, while the disease duration was significantly shorter than in the control groups. NFL correlated significantly with age in all groups, and the NFL levels of AIE patients were hardly higher than those of healthy elderly people published elsewhere. Conclusions: Our data indicate that the elevated NFL levels in AIE patients are most likely due to the higher age in this group and not due to the underlying inflammation. Unless larger prospective studies with intra-individual, longitudinal analyses and treatment responses would contradict our findings, NFL in serum might yet become a biomarker for disease activity and differential diagnosis.

RESUMEN

OBJECTIVE: Focal cortical dysplasias (FCDs) are a common cause of drug-resistant focal epilepsy but frequently remain undetected by conventional magnetic resonance imaging (MRI) assessment. The visual detection can be facilitated by morphometric analysis of T1-weighted images, for example, using the Morphometric Analysis Program (v2018; MAP18), which was introduced in 2005, independently validated for its clinical benefits, and successfully integrated in standard presurgical workflows of numerous epilepsy centers worldwide. Here we aimed to develop an artificial neural network (ANN) classifier for robust automated detection of FCDs based on these morphometric maps and probe its generalization performance in a large, independent data set. METHODS: In this retrospective study, we created a feed-forward ANN for FCD detection based on the morphometric output maps of MAP18. The ANN was trained and cross-validated on 113 patients (62 female, mean age ± SD =29.5 ± 13.6 years) with manually segmented FCDs and 362 healthy controls (161 female, mean age ± SD =30.2 ± 9.6 years) acquired on 13 different scanners. In addition, we validated the performance of the trained ANN on an independent, unseen data set of 60 FCD patients (28 female, mean age ± SD =30 ± 15.26 years) and 70 healthy controls (42 females, mean age ± SD = 40.0 ± 12.54 years). RESULTS: In the cross-validation, the ANN achieved a sensitivity of 87.4% at a specificity of 85.4% on the training data set. On the independent validation data set, our method still reached a sensitivity of 81.0% at a comparably high specificity of 84.3%. SIGNIFICANCE: Our method shows a robust automated detection of FCDs and performance generalizability, largely independent of scanning site or MR-sequence parameters. Taken together with the minimal input requirements of a standard T1 image, our approach constitutes a clinically viable and useful tool in the presurgical diagnostic routine for drug-resistant focal epilepsy.

Asunto(s)

RESUMEN

INTRODUCTION: Medical cannabis is increasingly discussed as an alternative treatment option in neurological diseases, e.g. epilepsy. Supporters and opponents base their propositions mostly on subjective estimates, they confuse cannabis in whole versus extracts and botanical versus synthesized. METHODS: Two hundred seventy five patients with any kind of epilepsy (56% female, 44% seizure free, 91% on medication) answered a survey on the knowledge, expectations, fears, and willingness to be treated with medical cannabis. Data were analyzed with regard to patient characteristics and clinical data from patient files. RESULTS: Overall, 70.5% of the patients were familiar with the possibility of medical cannabis treatment, 36.7% with its use in epilepsy. A minority of 10.9% gained the information from their physicians. The majority knew about organic compared to synthetic cannabis. The interest in further information is high (71.3%). Regression analysis (explaining 53.8% of the variance) indicated that positive expectations (in the order of relevance) were seizure control, relaxation, mood, and tolerability whereas fears mostly concerned addiction and delirant intoxication. Men showed a greater interest than women. CONCLUSION: Many epilepsy patients knew about medical cannabis, were interested in this treatment, and wanted more information. Expectations, however, appear to be based on the connotations of the whole substance cannabis with tetrahydrocannabidiol and its commonly known effects. Unfortunately, patients did not get their information from physicians, but mostly by other sources. In order to avoid prejudices and potentially harmful self-medication, physicians and healthcare providers are called to become familiar with the substance and to inform patients adequately.

Asunto(s)

RESUMEN

OBJECTIVE: To compare the effects of different surgical approaches for selective amygdalohippocampectomy in patients with pharmacoresistant mesial temporal lobe epilepsy with regard to the neuropsychological outcome and to replicate an earlier study employing a matched-pair design. METHOD: 47 patients were randomised to subtemporal versus transsylvian approaches. Memory, language, attentional and executive functions were assessed before and 1 year after surgery. Multivariate analyses of variance (MANOVAs) with presurgical and postsurgical assessments as within-subject variables and approach and side of surgery as between-subject factors were calculated. Additionally, the frequencies of individual performance changes based on reliable change indices were analysed. RESULTS: Seizure freedom International League Against Epilepsy (ILAE) 1a, was achieved in 62% of all patients without group difference. MANOVAs revealed no significant effects of approach on cognition. Tested separately for each parameter, verbal recognition memory declined irrespective of approach. Post hoc tests revealed that on group level, the subtemporal approach was associated with a worse outcome for verbal learning and delayed free recall as well as for semantic fluency. Accordingly, on individual level, more patients in the subtemporal group declined in verbal learning. Left side of surgery was associated with decline in naming regardless of approach. CONCLUSION: The main analysis did not confirm the effects of approach on memory outcome seen in our previous study. Post hoc testing, however, showed greater memory losses with the subtemporal approach. Previous findings were replicated for semantic fluency. The discrepant results are discussed on the background of the different study designs.

Asunto(s)

RESUMEN

Background: Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of epilepsy refractory to medical therapy. Among different surgical approaches, selective amygdalohippocampectomy has gained increasing interest for its rationale of isolated removal of the epileptogenic mesiotemporal area. Objective: To summarize our experience with surgical treatment of MTLE in 162 patients using the transsylvian approach and to analyze possible effects of length of hippocampal resection and postoperative gliosis on seizure and cognitive outcome. Methods: Clinical, radiological, histopathological and neuropsychological findings of 162 patients with MTLE who were operated by the senior author between 1993 and 2012 were retrospectively evaluated. Postoperative follow-up mounted up to 240 months (59 ± 56 months). Seizure outcome was available in 156 patients with minimum follow-up of 3 months. Extent of hippocampal resection was evaluated in 70 and postoperative gliosis in 62 of the 92 patients. Results were then correlated with seizure and cognitive outcome. Results: Of 134 patients with a follow-up of at least 1 year, 85 (63.4%) remained completely seizure free (Engel Ia) and 118 (88.0%) had a worthwhile improvement after surgery (Engel I+II). There was no perioperative death. Permanent morbidity was encountered in 4 patients (2.5%). Neither the extent of hippocampal resection nor postoperative gliosis correlated with seizure outcome or postoperative memory performance. Conclusion: Transsylvian selective amygdalohippocampectomy can be recommended as an adequate procedure for the surgical treatment of mesiotemporal epilepsy with favorable epileptological results and acceptable morbidity.

Asunto(s)

RESUMEN

PURPOSE: Epilepsy surgery is associated with a risk of cognitive deterioration, but improvement has also been reported. Improvements have mostly been attributed to seizure control, neglecting changes in drug treatment during the observation period. We evaluated whether changes of antiepileptic treatment affect cognitive outcome one year after epilepsy surgery. METHODS: This retrospective study evaluated the impact of quantitative and qualitative antiepileptic drug changes on postoperative outcome on cognition (executive functions, episodic memory) and mood in 116 epilepsy surgery patients, controlling the results for seizure outcome (seizure free yes/no) and site of surgery (87 temporal lobe, 29 extratemporal lobe resections). RESULTS: At baseline, 60% of all patients showed impairment in executive functions, 54% in memory, 49% in mood. Postoperatively, 65% of the patients were seizure free. Executive functions, memory, and mood improved in 22%, 10%, and 32%, respectively, and deteriorated in 15%, 21%, and 11%. Drugs were changed quantitatively (change of drug load) and qualitatively (optimization in regard to side effect profiles). According to MANCOVA and individual level analyses, executive functions changed significantly with altered drug load. This was confirmed by partial correlations when controlling for seizure outcome. Memory outcome was more strongly determined by site of surgery. Mood improved non-specifically. However, qualitative drug change had some positive effect on postoperative memory and mood. CONCLUSION: The data highlight the relevance of AED changes for cognitive outcome after epilepsy surgery. Drug load reduction and selection of drugs with favorable side effect profiles significantly release cognitive functions thereby supporting recovery after epilepsy surgery.

Asunto(s)

RESUMEN

We describe a 35-year-old male patient presenting with depressed mood and emotional instability, who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic awareness regarding autobiographical memories of the last 3 years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression, or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left >right). Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over 6 months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment, the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit, vocational reintegration was successfully in progress. In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting, and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with repeated assessments.

RESUMEN

BACKGROUND: Multiple cerebral cavernous malformations (mCCMs) are known as potentially epileptogenic lesions. Treatment might be multimodal. Management of patients with mCCMs and epilepsy is challenging. OBJECTIVE: To evaluate (1) algorhythmic therapeutic sequences in patients with epilepsy associated to mCCMs, (2) whether there are predictive parameters to anticipate the development of drug-resistant epilepsy, and (3) seizure after epilepsy surgery compared to conservatively-treated drug-resistant patients. METHODS: All inpatients and outpatients with epilepsy associated to mCCMs from 1990 to 2010 and follow-up >12 months available were retrospectively analyzed. RESULTS: Twenty-three patients matched inclusion criteria. Epilepsy became drug-resistant in 18/23 (78%) patients. No predictors were found for development of drug-resistant epilepsy. Median follow-up for both groups was 7.8 years. Nine patients did not qualify for surgical therapy and were treated conservatively. One patient of this cohort (11%) was seizure-free (International League Against Epilepsy [ILAE] class 1). Surgical treatment was performed in 9 patients; 7/9 (78%) of these patients were seizure-free (ILAE class 1) after epilepsy surgery for at least 12 months compared with 1/9 patients in the non-operated group. In 7/9 cases (78%) the largest CCM was resected. In 8/9 (89%) not all CCMs were resected. CONCLUSION: After initial diagnosis of epilepsy associated to mCCMs, a primary conservative approach is reasonable. Surgical treatment can be successful in a large fraction of cases with drug-resistant epilepsy where an epileptogenic lesion is identified. Cases where surgery is not undertaken are likely to remain intractable.

Asunto(s)

RESUMEN

OBJECTIVE: Hemispheric neurosurgery is an established treatment for severe epilepsy caused by extended unilateral brain pathology. However, it is still an unresolved question at which age surgery should best be performed. In light of decreasing plasticity and the cumulative impact of seizures and anticonvulsants on neurodevelopment, early surgery appears preferable. METHODS: We retrospectively investigated the medical, cognitive-behavioural and psychosocial long-term outcome (follow-up: 9.4 years (1.1-19.4)) of hemispherectomy as a function of age at surgery (early: <7 years/intermediate: 7-16 years/late: >16 years) based on a structured postal survey in a large patient sample (N=61/81, return rate: 75%). RESULTS: At follow-up, 45 (74%) patients were seizure free. Presurgical levels of intelligence were below average in most patients (79%) and postsurgical cognition largely resembled the presurgical capacities. Best seizure outcome was obtained for early surgery patients (90% seizure free). Patients with late surgery, however, exhibited higher presurgical and postsurgical intelligence and better psychosocial achievements. Binary logistic regression identified better presurgical intelligence and higher age at surgery as positive predictors of postsurgical intelligence. Lower presurgical intelligence and postsurgical seizure freedom predicted intellectual pre-post improvements. CONCLUSIONS: Our data confirm the efficacy and cognitive safety of hemispheric surgeries performed at different ages. Eligible older and high functioning patients can be perfect candidates. Presurgical intelligence serves as indicator of the functional integrity of the contralateral hemisphere, which mainly determines postsurgical cognition and psychosocial outcome. Seizure freedom promotes cognitive improvement. As many unknown factors determined age at surgery, our retrospective data neither question early surgeries nor suggest postponing surgery.

Asunto(s)

RESUMEN

Despite considerable research on EEG-feedback of slow cortical potentials (SCPs) for seizure control in epilepsy, the underlying mechanisms and the direct effects on intracerebral pathological activity within the focal area remain unclear. Intrahippocampal EEG recordings from four patients with temporal lobe epilepsy and implanted electrodes were analyzed with regard to spike activity and power in 10 frequency bands (0.5-148Hz) during SCP feedback based on surface recordings (position Cz). Trials with positive, negative and indifferent SCPs were contrasted. Three of the four patients showed changes in spike activity during SCPs, but these were inconsistent between patients, and resulted in increased and decreased activity in both positive and negative SCPs. Spectral analysis revealed that in all patients, positive surface shifts showed a bi-hemispheric higher power in the high-frequency activity above 40Hz. Two patients showed a higher power also during negative shifts, both in high-frequency activity and one in most other frequency bands. Feedback-related power effects did not differ between focal and non-focal side. The inconsistent change in spiking activity and the lack of decrease of power in pathology associated frequency bands during SCPs show that these SCPs do not decrease pathological activity within the epileptic focus. A possible relation of higher power in high-frequency activity during positive SCPs to cognitive processes, such as memory functions, is discussed.

Asunto(s)

RESUMEN

Clarification of the cortical mechanisms underlying auditory sensory gating may advance our understanding of brain dysfunctions associated with schizophrenia. To this end, data from nine epilepsy patients who participated in an auditory paired-click paradigm during pre-surgical evaluation and had grids of electrodes covering temporal and frontal lobe were analyzed. A distributed source localization approach was applied to the intracranial P50 response and the Gating Difference Wave obtained by subtracting the response to the second stimuli from the response to the first stimuli. Source reconstruction of the P50 showed that the main generators of the response were localized in the temporal lobes. The analysis also suggested that the maximum neuronal activity contributing to the amplitude reduction in the P50 time range (phenomenon of auditory sensory gating) is localized at the frontal lobe. Present findings suggest that while the temporal lobe is the main generator of the P50 component, the frontal lobe seems to be a substantial contributor to the process of sensory gating as observed from scalp recordings.

Asunto(s)

RESUMEN

Effects of stimulus repetition are investigated in short-term habituation experiments. In these experiments, trains of stimuli are applied with longer intervals of no stimulation between the trains. In scalp recordings, an amplitude and latency decrease of the auditory N100 is usually observed at the beginning of the train. This contrasts to a recent finding with intracranial recordings, exhibiting an effect on N100 amplitude, but not on its latency. In the current study, P50 and N100 were simultaneously recorded intra- and extracranially in epilepsy patients. The amplitudes of P50 and N100 decreased in both recordings, whereas the P50 latency was not significantly affected. A latency decrease was revealed for the extracranially recorded N100, but not for the intracranial N100. This dissociation between the intracranial and scalp recordings might be explained by a different sensitivity of the two measurements for N100 generators.

Asunto(s)

RESUMEN

It is still a matter of debate at which time point faces are recognized as familiar, with some studies claiming a relatively early face recognition and others later effects of familiarity. The authors report on effects of famousness of depicted persons and stimulus repetition on intracranially recorded event-related potentials. Famousness resulted in an increased latency of the N200 component, as well as in an increased amplitude of a later long-lasting potential (N700). In contrast, repetition led to an increased amplitude of the N200 but no increase of its latency. They suppose that the recognition of faces becomes observable within the N200 latency range and that the increased N200 latency reflects a feature processing additional to the holistic face processing.

Asunto(s)

RESUMEN

Mismatch negativity (MMN) is elicited by discernible changes in an otherwise regular stream of auditory stimulation and reflects a pre-attentive detection mechanism. In the current study, auditory evoked potentials were recorded intracranially and electrode contacts sensitive for stimulus deviance were selected in order to further elucidate the contribution of different brain areas to MMN generation. Data were obtained from patients with frontal and temporal lobe epilepsy undergoing a presurgical evaluation by subdural and depth electrodes. In 13 of 29 patients under investigation an intracranial MMN could be observed, while in four other patients a response recovery of the N100 was revealed, mimicking an MMN. Most electrodes with an MMN signal were located in or close to the superior temporal lobe. In two patients an MMN was observed at electrode contacts over the lateral inferior frontal cortex and in one patient at a frontal interhemispheric electrode strip, giving evidence for a participation of the frontal gyrus in MMN generation. Current findings have, however, to be interpreted with caution owing to the placement and limited extension of the used electrode arrays.

Asunto(s)

RESUMEN

At an interstimulus interval (ISI) of 500-ms stimulus repetition leads to a strong decrease in cortical response. The functional foundation of this response suppression (or sensory gating) is yet not fully understood. Experiments on short-term habituation using the same stimulus material as sensory gating experiments and same ISI might help to elucidate the mechanisms behind the P50 suppression. Event-related potentials were recorded intracranially in epileptic patients undergoing presurgical evaluation with subdural and depth electrodes. Stimulus material consisted of trains of six clicks, with the last stimulus deviating in pitch and duration. P50 and N100 were calculated for each stimulus in the train separately and compared by analysis of variance (ANOVA). A highly significant amplitude reduction was found from the 1st to 2nd stimulus for both P50 and N100. From the 2nd to 5th stimulus no further amplitude decrease was observable. The deviating 6th stimulus led to a response recovery of both components, but the P50 elicited by the 6th stimulus was still smaller than the P50 of the 1st stimulus. Current results indicate that the P50 suppression as investigated in sensory gating experiments seems to be completed after the 2nd stimulus.

Asunto(s)

RESUMEN

It remains unclear whether uncontrolled epilepsy causes mental decline. This longitudinal study contrasts change of memory and nonmemory functions in 147 surgically and 102 medically treated patients with temporal lobe epilepsy. All participants were evaluated at baseline (T1) and after 2 to 10 years (T3). Surgical patients underwent additional testing 1 year postoperatively (T2). Data were analyzed on an individual and group level. Sixty-three percent of the surgical and 12% of the medically treated patients were seizure-free at T3. Fifty percent of the medically treated and 60% of the surgical patients showed significant memory decline at T3 with little change in nonmemory functions (difference not significant). Surgery anticipated the decline seen in the medically treated group and exceeded it when surgery was performed on the left, or if seizures continued postoperatively. Seizure-free surgical patients showed recovery of nonmemory functions at T2 (p < 0.001) and of memory functions at T3 (T3, p = 0.03). Multiple regression indicated retest interval, seizure control, and mental reserve capacity as predictors of performance changes. In addition, psychosocial outcome was better when seizures were controlled. In conclusion, chronic temporal lobe epilepsy is associated with progressive memory impairment. Surgery, particularly if unsuccessful, accelerates this decline. However, memory decline may be stopped and even reversed if seizures are fully controlled.

Asunto(s)

RESUMEN

Our knowledge of longer term outcome in psychogenic nonepileptic seizures (PNESs) patients is limited; we know less still about factors predicting prognosis. This study was intended to describe outcome in a large cohort and to identify predictive clinical and psychological factors to generate new ideas for treatment. One hundred sixty-four adult patients with PNESs (66.7%) responded to outcome, personality, and psychosymptomatology questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], Dissociative Experiences Scale, and Screening Test for Somatoform Symptoms) a mean of 11.9 years after manifestation and 4.1 years after diagnosis of PNES. Additional clinical data were retrieved from hospital records. The responses showed that 71.2% of patients continued to have seizures and 56.4% were dependent on social security. Dependence increased with follow-up. Outcome was better in patients with greater educational attainments, younger onset and diagnosis, attacks with less dramatic features, fewer additional somatoform complaints, and lower dissociation scores. Better outcome was associated with lower scores of the higher order personality dimensions "inhibitedness," "emotional dysregulation," and "compulsivity" but not "dissocial behavior" (DAPP-BQ). Outcome in PNESs is poor but variable. Clinical and personality factors can be used to provide an individualized prognosis. By generating a patient-specific profile, they show particular maladaptive traits or tendencies that can identify goals for psychological therapy.

Asunto(s)

Asunto(s)

RESUMEN

We present three patients with left-sided temporal lobe epilepsy who exhibited preoperatively a neuropsychological pattern characteristic for interhemispheric language transfer (marked nonverbal memory deficits, relatively preserved verbal memory and language performance). The Wada test indicated atypical language dominance in two patients, but one patient was clearly left hemispheric language dominant. All patients showed a marked recovery of nonverbal memory after left-sided surgery. Results are discussed with respect to memory transfer and plasticity for memory functions in the adult brain.

Asunto(s)