Causes, presentation and outcome of lesional adult onset mediotemporal lobe epilepsy.

BACKGROUND AND AIMS: Mediotemporal lobe (MTL) epilepsy (MTLE) is particularly frequent among human localisation related epilepsies. MTLE usually starts before adulthood and is most frequently associated with hippocampal sclerosis (HS). Here, aetiologies, disease courses and outcomes of adult onset MTLE patients treated at this tertiary epilepsy centre are studied. METHODS: We collected all patients studied between January 1999 and December 2005 fulfilling the following criteria: (1) MTLE manifestation at age > 20 years; (2) time between disease manifestation and assessment < or = 6 years; (3) MTL lesion on brain MRI; and (4) neuropsychological test battery applied. The diagnoses were classified and paraclinical data, neuropsychological performances, and seizure and memory outcomes were documented. RESULTS: Diagnoses in the 84 patients (mean age 42 years at MTLE onset) were: limbic encephalitis (LE), n = 23 (27%); HS (unrelated to inflammation), n = 18 (22%); tumours I/II(o), n = 12 (14%); amygdala lesions (increased volume and T2/FLAIR signal), n = 11 (13%); and other, n = 20 (24%). Visible MTL affection was frequently bilateral in patients with LE (57%) and HS (22%). These groups also showed the poorest memory performance. Patients with amygdala lesions were the oldest (mean age 52 years); their lesions were in part immune mediated and in part probably dysplastic. Treatment dependent seizure outcomes were similar to published data without restriction to adult onset cases. Under conservative therapy, memory performance remained stable in patients with HS but improved in a proportion of patients with LE. CONCLUSIONS: The data suggest that LE is a common and a previously underestimated cause of MTLE in this age group. Its prognosis is variable. Amygdala lesions, also, are in part encephalitic in nature.

Greater functional recovery after temporal lobe epilepsy surgery in children.

The purpose of our study is to evaluate whether children recover better than adults from memory deficits as a consequence of temporal lobe surgery. We compared 3 and 12 month outcomes obtained in children and adults with medically refractory epilepsy. Each candidate underwent temporal lobe resection for seizure control and children were matched with regard to pathology, onset of epilepsy, side of surgery and type of surgery with adults (N = 30 for each group, mean age at surgery 13 versus 30 years). Three months after surgery, both left-resected groups displayed a significant decline in verbal learning capacity. During the following 9 months, only the children recovered and were able to reach their preoperative level 1 year after surgery. The left-resected adults remained, for the most part, on their low level and one year after surgery, they were still significantly worse than at the time of their preoperative examination. The right-resected adults experienced a deterioration in visual memory 1 year after surgery relative to the results of the short-term follow-up; the children improved. The children also had a better outcome with regard to attentional functions and, as a trend, a better seizure outcome (Engel Outcome I--1 year after surgery: 63% adults, 80% paediatric patients). Our neuropsychological data provide evidence of greater plasticity and compensational capacity in childhood. The results can be taken as a strong argument for early surgical intervention.

Introducing natural thermoplastic shellac to microfluidics: A green fabrication method for point-of-care devices.

We present a sustainable fabrication method for cheap point-of-care microfluidic systems, employing hot embossing of natural shellac as a key feature of an energy-efficient fabrication method that exclusively uses renewable materials as consumables. Shellac is a low-cost renewable biomaterial that features medium hydrophilicity (e.g., a water contact angle of ca. 73°) and a high chemical stability with respect to common solvents such as cyclohexane or toluene, rendering it an interesting candidate for low-cost microfluidics and a competitor to well-known systems such as paper-based or polydimethylsiloxane-based microfluidics. Moreover, its high replication accuracy for small features down to 30 µm lateral feature size and its ability to form smooth surfaces (surface roughness Ra = 29 nm) at low embossing temperatures (glass transition temperature Tg = 42.2 °C) enable energy-efficient hot embossing of microfluidic structures. Proof-of-concept for the implementation of shellac hot embossing as a green fabrication method for microfluidic systems is demonstrated through the successful fabrication of a microfluidic test setup and the assessment of its resource consumption.

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs resections plus Multiple Subpial Transections), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the three month follow-up examination, patients with temporal lobectomy had improved frontal functions, while patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MST's of precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favorable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated to frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Evidence of very fast memory consolidation: an intracarotid amytal study.

This study provides evidence from intracarotid amobarbital tests (IAT) in patients with epilepsy that complete suppression of the electrophysiological activity of the left language-dominant hemisphere through left IAT does not impair memory for verbal information given 1 min or immediately before the injection of the barbiturate. Although language functions were completely disrupted and patients were unable to encode new information during the left IAT, pre/post memory was as good as in the right IAT. This lack of retrograde amnesia leads to the conclusion that a relatively stable representation of events is achieved within seconds after encoding. The results contradict models which assume that short-term memory is based on purely electrophysiological processes.

The hippocampal contribution to verbal fluency in patients with temporal lobe epilepsy.

We report the effects of hippocampal and non-hippocampal temporal-lobe dysfunction on verbal fluency performance. Quantitative aspects of semantic and phonemic fluency performance were examined in 46 patients with right- or left-temporal-lobe epilepsy and 20 healthy controls. A pattern of fewer words generated on semantic rather than phonemic fluency tasks was found among patients with damage to hippocampal structures. This pattern was not obtained in patients with non-hippocampal temporal-lobe damage, suggesting that the hippocampus plays a crucial role in semantic fluency performance. An interesting lateralization effect was obtained. Among patients with left temporal-lobe involvement, fluency performance was impaired regardless of whether the hippocampus was involved. In contrast, among patients with right temporal-lobe involvement, fluency performance was impaired only when the hippocampus was involved.

Relational verbal memory processing in patients with temporal lobe epilepsy.

Patients with left temporal lobe epilepsy (LTLE) have been shown to demonstrate impaired categorization in semantic memory tasks leaving open the question whether this is due to problems with active categorization or to problems with consolidation/retrieval of relations. 35 patients with left or right temporal lobe epilepsy (LTLE, RTLE) and 20 healthy controls performed three verbal learning and memory tests differing in the relational distance between the items to be learned (unrelated, low associative, high associative). In order to separate the memory component in relational memory processing, we avoided problems in active categorization and perception of semantic relations by presenting category members already clustered in the order of category membership, and by checking whether the patients had actually noticed the categories. In controls and in patients with RTLE, both semantic conditions significantly improved the test performance. LTLE-patients showed the worst test performance independent of the test condition. Their performance improved under the high associative condition, but they did not at all profit from the low associative condition. Although the semantic tasks had no demand on active clustering and although all LTLE-patients noticed the relational properties very well, they could not make use of the offered clusters. They demonstrated significantly more "item specific" than "relational" encoding than the other groups. This was pronounced in the low associative condition but became evident also in the high associative condition. In contrast to the other groups, the order in recall (clustering) deteriorated with passing time in LTLE-patients. In conclusion the data provide evidence of impaired semantic relational processing in LTLE. The impairment depends on the relational properties of the material to be learned, in that it increases with the relational distance between the memory contents. Because the tasks did not demand active clustering, we can attribute this impairment to deficits in relational encoding/retrieval which would be consistent with current opinions of the role of temporolimbic structures in relational memory processing.

The performance-complaint relationship in patients with epilepsy: a matter of daily demands?

Weak relationships have been reported between subjective complaints of memory deficits and memory performance in neuropsychological tests in patients with temporal lobe epilepsy (TLE). This study investigated whether the individual exposure to cognitive demands in daily life contributes to cancel out the performance-complaint relationship in such a way that cognitive deficits are more likely experienced by patients in 'high demand' than in 'low demand' situations. Neuropsychological performance, subjective complaints and daily demands were assessed in 57 TLE-patients 1 year after a temporal lobe surgery. Data were analyzed using non-parametric statistical techniques. Results indicated surprisingly close relationships between subjective complaints and memory performance in standardized tests. The highest correlations were found for the non-verbal memory test. Cognitive demands did not counteract this result. Contrary to our expectation, lower demands were associated with stronger subjective complaints. Cognitive demands thus appeared not as a modulating factor that weakens the relationship between test deficits and subjective complaints in patients with TLE.

Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy.

Outcome studies concerning memory after pediatric temporal lobe surgery in the treatment of epilepsy are rare and have not yielded consistent results. In the present study, 55 children and adolescents with temporal lobe epilepsy (TLE; 26 left, 29 right, 6-17 years) performed a verbal memory test before and 3 as well as 12 months after different types of temporal lobe resections (anterior lobectomy, amygdalo-hippocampectomy (AH), lesionectomy (LX)). Groups did not significantly differ before surgery. Three months after surgery, the left resected group showed a decline in learning and delayed recall, and performed significantly lower than the right resected group. Recoveries were evident 1 year after surgery. The postoperative memory declines were associated with a left-sided resection and a higher preoperative performance. Comparisons on the different resection types suggest a special risk in patients undergoing a left-sided AH. In summary, our results indicate a functional association of verbal memory functions with the left temporal lobe similar to findings in adult patients. Declines after left-sided temporal resections seem to be reversible at least for part of the children, perhaps due to the greater plasticity of the immature brain.

Neuropsychological Outcome in Children after Frontal Lobe Epilepsy Surgery.

We investigated the neuropsychological performance of children with frontal lobe epilepsy (FLE, n = 12) before and 1 year after surgery. Children with temporal lobe epilepsy (TLE, n = 12) were included as control group. Preoperatively, children with FLE had a significantly higher IQ than children with TLE, but were significantly more often impaired in manual motor coordination. Postoperatively, both groups improved in attention, short-term and long-term memory, and manual coordination, although the latter was not significant. Neuropsychological outcome in FLE patients was not better in seizure-free patients than in patients with continuing seizures. To avoid deterioration in language functions of patients in whom surgery involved left area 44, correspondence of results in cortical stimulation and intracarotid amytal test may be essential. All in all, our data indicate a favorable cognitive outcome in children 1 year after frontal lobe surgery.

The validity of the Child Behavior Checklist for children with epilepsy.

The validity of the Child Behavior Checklist (CBCL) for patients with epilepsy has been questioned, because several items may reflect seizure semiology rather than habitual behavior. This study compared a standard version of the CBCL with an adjusted version that excluded those ambiguous items. Participants were 58 pediatric patients with epilepsy who were assessed preoperatively and 1 year after successful surgical treatment. Before surgery, the adjusted version indicated significantly lower values for the scales Attention Problems, Thought Problems, and Total Problems than the standard version. After surgery, the difference between the standard and adjusted versions and the scores for the ambiguous items were unchanged, although all patients were completely seizure free at that time. Elevated scores on the ambiguous items thus probably reflect real behavioral problems and are not due to confusion with seizure semiology. The results support the CBCL as a valid assessment tool in children with epilepsy.

[A new questionnaire for recognizing cognitive problems in children and adolescents]. / Kognitive Probleme bei Kindern und Jugendlichen : Vorstellung eines Fragebogens.

BACKGROUND: Patients with psychiatric or neurologic disease often suffer from neuropsychologic problems. The purpose of this study was to present a parental questionnaire (KOPKIJ) that assesses neuropsychologic problems in children and adolescents between 6 and 16 years of age. METHODS: We tested theoretical analysis, standardization, and validation of the questionnaire in 352 healthy controls and 116 pediatric patients with epilepsy. RESULTS: The objectivity of this standardized questionnaire can be considered high, and the reliability of the subscales is satisfying. Epileptic patients had higher scores than healthy controls, and the validation displayed reasonable connections with clinical factors and the results of neuropsychological evaluation. CONCLUSION: The KOPKIJ allows an orientating appraisal clear picture of cognitive problems of children and adolescents at home and at school, simplifies anamnesis, and eases the planning of therapy strategies.

Surgical outcome in a group of low-IQ patients with focal epilepsy.

PURPOSE: Because a low IQ score indicates global brain damage, several authors consider it a contraindication for resective epilepsy surgery. This study reports the postoperative results of a small group of subaverage-intelligence patients with epilepsy who underwent focal resections. METHODS: We report on 16 patients who underwent focal resections (no callosotomy or hemispherectomy). All had IQ's <85 and were >13 years of age at the time of surgery. Low IQ was psychometrically assessed (mean IQ = 70) and confirmed by the patients' educational/occupational status. Clinical characteristics, findings from the preoperative workup, and the surgical treatment are described in detail. Postoperative outcome was evaluated with respect to seizure relief and cognitive/ socioeconomic development. RESULTS: Three months after surgery, 14 (87%) of 16 patients were completely seizure free, and nine (64%) of 14 were seizure free at the 1-year follow-up. Patients' cognitive abilities and socioeconomic status were mostly unchanged and in some cases improved. Seizure outcome was not related to IQ level, and there was no evidence of multiple epileptic foci in the patients with continued seizures. CONCLUSIONS: A low IQ level does not entail the presence of extended epileptogenic regions or multiple epileptic foci. Seizure-relief rates in our group concurred with the rates in patients of average intelligence, and the cognitive/socioeconomic outcome was favorable. We conclude that focal surgery in intellectually impaired patients can be recommended if the preoperative diagnostics confirm a circumscribed seizure onset.

Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy.

OBJECTIVES: Existing speculations regarding the cognitive functions of the right hippocampus suggest a special involvement in non-verbal memory functions. However, all supporting evidence in epileptic patients came from postoperative studies that did not consider the preoperative functioning level. The present study investigates in patients with right temporal lobe epilepsy (RTLE), both preoperatively and postoperatively, the role of the right hippocampus for visual memory, visuoconstruction, and spatial visualisation. METHODS: Two groups of patients with RTLE with and without right hippocampal damage (HC+/n=15 v HC-/n=13) were set up retrospectively thereby taking into account the surgical treatment (selective amygdalohippocampectomy v temporal resections sparing the hippocampus), the postoperative pathological findings (hippocampal sclerosis in the HC+ group) and the seizure outcome (all seizure free). The two groups were compared with regard to their neuropsychological performance preoperatively and 3 months after temporal lobe surgery. RESULTS: The preoperative results indicated impaired visual memory performance only for the HC+ patients, whereas the HC- patients exhibited no deficiencies in any of the assessed functions. Postoperatively, both groups exhibited partially improved performances. The type of surgical treatment had no different effects on the postoperative performance changes. CONCLUSIONS: The results suggest that hippocampal damage is the major cause of non-verbal memory deficiencies in preoperative patients with right temporal lobe epilepsy. Hence the results support and extend findings from previous postoperative studies. Right hippocampal resections did not increase the preoperative visual memory deficiencies, thus supporting the view that right temporal lobe resection in general bears only small risks for cognitive deteriorations.

Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy.

A wealth of animal and human research has pointed to a significant involvement of the temporal lobes in memory processing, and yet the different functional roles of temporal cortical vs. mesial structures remain unclear. We studied verbal declarative memory, by using a word list paradigm that differentiates among learning (immediate recall), memory (delayed recall), and recognition, in epilepsy patients being considered for surgical resection of the left temporal lobe. Verbal memory was evaluated preoperatively and during the recording of intracranial event related potentials and postoperatively after selective hippocampectomy, temporal cortical lesionectomy, or anterior two-thirds en bloc temporal lobe resection procedures. Preoperative differences in verbal memory performance as a function of differences in underlying neuropathology, concurrent event-related potentials, and specific patterns of postoperative memory impairments lead to converging evidence that verbal declarative memory relies on a synergistic interaction of at least two functionally distinct brain systems. Material-specific data acquisition, or working memory, is mediated by neocortical temporal structures, whereas long-term consolidation/retrieval is particularly mediated by temporomesial structures. In contrast to the left temporal neocortex, the function of the temporomesial system appears to be material nonspecific. Apparently, its preferential involvement in verbal memory is due to its close interaction with overlying neocortical structures that are specialized for language processing.

An open study of tacrolimus therapy in Rasmussen encephalitis.

Seven patients with Rasmussen encephalitis (RE) were treated with the immunosuppressant tacrolimus and followed for a median of 22.4 months. They were compared with 12 historical untreated RE patients (median follow-up 13.9 months). The tacrolimus-treated patients had a superior outcome regarding neurologic function and progression rate of cerebral hemiatrophy but no better seizure outcome. No treated patient, but 7 of 12 control patients, became eligible for hemispherectomy. Tacrolimus did not have any major side effects.

Clinical and neuropsychological characteristics of pediatric epilepsy patients with atypical language dominance.

Studies on intracarotid amobarbital procedures (IAP) in pediatric patients are rare and mainly focus on practicability aspects. Very few studies have reported characteristics of children with atypical language dominance. We compared children with left-sided focal epilepsy and atypical (i.e., right or bilateral) versus left-sided language representation (n=12 versus 17). Our results indicate a higher incidence of left handedness, extratemporal lesions, an earlier onset of epilepsy, and a neuropsychological "crowding effect" with distinct nonverbal memory deficits in the atypical group. We conclude that atypical language representation in children with left-sided epilepsy is associated with similar characteristics as in adults. It is recommended that the possibility of a language shift in the presurgical workup of pediatric patients be considered, particularly if a left-hemispheric epileptic focus is suspected.