Neuropsychology of late-onset epilepsies.

In an increasingly ageing society, patients ageing with epilepsy and those with late-onset epilepsies (LOE) represent a challenge for epilepsy care and treatment. Senescence itself bears risks of pathologies which in the form of acute focal damage (e.g. stroke) or slowly progressive degenerative damage can cause seizures and substantial cognitive impairment. There is converging evidence from studies in LOE that cognitive impairments are present from epilepsy onset before treatment is initiated and may even precede the emergence of seizures. This suggests that these impairments (like the seizures) are expressions of the underlying disease. Indeed, both seizures and cognitive impairments can be early indicators of disease conditions which lead to mental decline. Cognitive decline over time poses the challenge of disentangling the interrelation between seizures, treatment effects and underlying disease. This issue must be considered as some of the etiologies for causing neuropsychological decline can be addressed. Medication and active epilepsy can contribute to impairments and their impact may be reversible. Dementia is rare if seizures are what has brought the person to attention, and if this is not accompanied by other slowly developing features (such as cognitive of psychiatric changes). From a neuropsychological point of view choosing the right screening tools or assessments, obtaining the history and timeline of impairments in relation to epilepsy, and most importantly longitudinally following the patients regardless of whether epilepsy is ultimately controlled or not appear essential.

Cognitive disorders in epilepsy II: Clinical targets, indications and selection of test instruments.

This is the second of two narrative reviews on cognitive disorders in epilepsy (companion manuscript: Cognitive disorders in epilepsy I: Clinical experience, real-world evidence and recommendations). Its focus is on the clinical targets, indications, and the selection of neuropsychological test instruments. Cognitive assessment has become an essential tool for the diagnosis and outcome control in the clinical management of epilepsy. The diagnostics of basic and higher brain functions can provide valuable information on lateralized and localized brain dysfunctions associated with epilepsy, its underlying pathologies and treatment. In addition to the detection or verification of deficits, neuropsychology reveals the patient's cognitive strengths and, thus, information about the patient reserve capacities for functional restitution and compensation. Neuropsychology is an integral part of diagnostic evaluations mainly in the context of epilepsy surgery to avoid new or additional damage to preexisting neurocognitive impairments. In addition and increasingly, neuropsychology is being used as a tool for monitoring of the disease and its underlying pathologies, and it is suited for the quality and outcome control of pharmacological or other non-invasive medical intervention. This narrative review summarizes the present state of neuropsychological assessments in epilepsy, reveals diagnostic gaps, and shows the great need for education, homogenization, translation and standardization of instruments.

Cognitive outcome of pediatric epilepsy surgery across ages and different types of surgeries: A monocentric 1-year follow-up study in 306 patients of school age.

OBJECTIVE: The neuropsychological outcome of pediatric epilepsy surgery has been reported before, but only few studies compared different major types of surgery in differentially located epilepsies. METHODS: Neuropsychological performance of 306 children and adolescents (ages 6-17 years) were assessed before and one year after epilepsy surgery. Individual impairments, changes into and out of impairment, as well as intraindividually meaningful positive or negative changes were examined. Regression analyses addressed the effects of site, side, pathology, type of surgery, seizure outcome, and drug change on the cognitive and behavioral domains. RESULTS: Preoperatively 85% of the patients had cognitive impairments in at least one domain, 71% had behavioral problems. Postoperatively the number of impaired patients dropped considerably: 21-50% of the patients changed from impaired to unimpaired, individually significant gains were registered in 16-42%. Seizure freedom was achieved in 81% of all patients. The number of antiepileptic drugs decreased significantly. Seizure freedom, a younger age at evaluation, a later age at onset, a lower antiepileptic drug load, and less baseline damage predict better cognitive and behavioral outcomes. Gender, pathology, localization, and lateralization had little or no impact. CONCLUSION: Differentially located and lateralized epilepsies hardly differed in cognition and behavior indicating nonspecific developmental rather than domain specific impairments. Childhood epilepsy surgery is very successful and the functional improvements one year after surgery confirm the general relevance of baseline damage, mental reserve capacities, functional plasticity, the preservation of functional tissues and the functional release due to seizure freedom and drug load reduction.

Ten things every neurologist needs to know about neuropsychological assessments and interventions in people with epilepsy.

This paper describes 10 core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the following headings. (1) A neuropsychological assessment is a collaborative investigation. (2) Assessment prior to treatment allows for the accurate assessment of treatment effects. (3) The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. (4) Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. (5) Patients' subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. (6) The results from a neuropsychological assessment can be used to maximize the educational and occupational potentials of people with epilepsy. (7) Not all patients are able to engage with a neuropsychological assessment. (8) There are limitations in assessments conducted in a second language with tests that have been standardized on different populations from that of the patient. (9) Adequate intervals between assessments maximize sensitivity to meaningful change. (10) Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.

Cognitive outcomes more than 5 years after temporal lobe epilepsy surgery: Remarkable functional recovery when seizures are controlled.

PURPOSE: Epilepsy surgery can be a successful treatment option for temporal lobe epilepsy but there are concerns about accelerated memory decline in long-term follow-up. METHOD: 161 adult operated (77 right, 84 left temporal resections) versus a heterogeneous group of 208 non-operated patients with focal epilepsies were consecutively recruited and re-evaluated focusing on memory, executive functions, and vocational outcome after follow-up intervals of >5 years (5-22 years, mean 8 ± 3 years). RESULTS: Major losses in the operated group manifest early, at one-year follow-up. Few patients declined further. Long-term changes after surgery did not differ from those observed without surgery. The factor "surgery" caused verbal memory decline, "seizure freedom" (operated 48%, non-operated 17%) was associated with recovery of verbal memory, and "drug reduction" positively affected the course of executive functions. In terms of the critical function of verbal memory, only 3-17% of seizure-free patients showed long-term decline whereas 16-20% showed improvement (operated and non-operated). Persistent seizures were associated with decline in 12-37% and improvement in 4-12% of patients. Improvement was related to longer retest intervals and was stronger in younger patients. Independent of surgery or seizure outcome, the vocational status remained unchanged or change was negative (22%) rather than positive (3%). CONCLUSIONS: Patients' cognitive course 5-22 years after surgery is stable and may even be positive if epilepsy is controlled and drug load reduced. Depending on seizure outcome, recovery is more frequently observed than continuing decline. Recovery, however, takes time and age is a limiting factor.

[Stereotactic laser thermocoagulation in epilepsy surgery]. / Stereotaktische Laserthermokoagulation in der Epilepsiechirurgie.

In common with other stereotactic procedures, stereotactic laser thermocoagulation (SLT) promises gentle destruction of pathological tissue, which might become especially relevant for epilepsy surgery in the future. Compared to standard resection, no large craniotomy is necessary, cortical damage during access to deep-seated lesions can be avoided and interventions close to eloquent brain areas become possible. We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase® and NeuroBlate®; CE marks pending). Both systems are coupled with magnetic resonance imaging (MRI) and MR thermometry, thereby increasing patient safety. We report the published clinical experiences with SLT in epilepsy surgery (altogether approximately 200 cases) with respect to complications, brain structural alterations, seizure outcome, neuropsychological findings and treatment costs. The rate of seizure-free patients seems to be slightly lower than for resection surgery. Due to the inadequate quality of studies, the neuropsychological superiority of SLT has not yet been unambiguously demonstrated.

Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy.

OBJECTIVES: Whether and when to immunologically treat epilepsy patients with suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. METHODS: This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy. RESULTS: All patients had seizures, amygdala and/or -hippocampal enlargement, subjective cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were impaired in executive or memory functions, 39% (10/25) depressed, 81% were on antiepileptic drugs when pulse therapy started. After a median follow-up of 18 months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27) showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical changes did not correlate to each other. Outcomes could not be predicted. CONCLUSION: Immunological treatment of suggested AB-negative LE showed reasonable seizure control, MRI and cognitive improvements. Treatment success was not predictable from clinical features, nor definitely attributable to immunological treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we suggest that in presence of mild manifestations, and after initiating antiepileptic drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be documented before immunosuppressive treatment is initiated.

Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis.

OBJECTIVE: To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies. METHODS: Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption. RESULTS: Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p<0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p<0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p<0.05) over time. CONCLUSIONS: Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.

Intracranial EEG correlates of implicit relational inference within the hippocampus.

Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future decision making.

The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding.

Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014. This Conference Proceedings provides a summary of the conference proceedings. Specifically, the following topics are discussed: (i) role of comorbidities in epilepsy diagnosis and management, (ii) role of antiepileptic medications in understanding the relationship between epilepsy and neurobehavioral and cognition problems, and (iii) animal data and diagnostic approaches. Evidence to date, though limited, strongly suggests a bidirectional relationship between epilepsy and cognitive and psychiatric comorbidities. In fact, it is likely that seizures and neurobehavioral problems represent different symptoms of a common etiology or network-wide disturbance. As a reflection of this shared network, psychiatric comorbidities and/or cognition problems may actually precede the seizure occurrence and likely get often missed if not screened.

Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies.

PURPOSE: Temporal lobe epilepsy with antibodies (abs) against the glutamic acid decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological syndrome. Here we evaluate the therapy response to various immunotherapies and epilepsy surgery in this syndrome. METHOD: All patients with GAD-TLE and follow-up data and stored serum and CSF samples, identified and treated at the Bonn centre from 2002 to 2010, were studied retrospectively. Seizure freedom for ≥1 year and reduction of ≥50%, i.e. therapy response, were assessed. GAD-ab titres and neuropsychological performances were documented prior and after individual interventions. RESULTS: Thirteen patients with GAD-TLE were identified with the following seizure responses: corticosteroids (5 responders out of 11 treated patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved sustained seizure freedom apart from one patient. This patient was on antiepileptic drug treatment after discontinuation of immunotherapy. CONCLUSION: The seizure response to immunotherapies in patients with GAD-TLE was poor. Corticosteroids were the most effective regarding seizure response. Especially the poor effects of apheresis therapies support the idea that GAD-abs are not directly pathogenic. None of three patients was seizure-free after temporal lobe surgery suggesting that GAD-TLE patients respond worse than others to this type of intervention. Our results reflect the chronic course of the disease with low likelihood for patients with GAD-TLE to attain long-term seizure freedom.

Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.

Cognitive-behavioral screening in elderly patients with new-onset epilepsy before treatment.

OBJECTIVES: Cognitive comorbidity at epilepsy onset reflects disease severity and provides a baseline estimate of reserve capacities with regard to the effects of epilepsy and its treatment. Given the high incidence of epilepsy at an older age, this study analyzed objective and subjective cognition as well as quality of life in elderly patients with new-onset focal epilepsy before initiation of anti-epileptic treatment. MATERIALS AND METHODS: A total of 257 untreated patients (60-95 years of age) with new-onset epilepsy underwent objective assessment of executive function (EpiTrack) and performed subjective ratings of cognition (Portland Neurotoxicity Scale) and quality of life (QoL; QOLIE-31). RESULTS: According to age-corrected norms, 58% of patients (N=257) demonstrated deficits in executive function; major determinants were cerebrovascular etiology, neurological comorbidity, and higher body mass index. Subjective ratings indicated deficits in up to 27% of patients. Self-perceived deficits were associated with neurological, cardiovascular, and/or psychiatric comorbidity, whereas poorer QoL was related to neurological comorbidity and female gender. Objectively assessed executive functions correlated with subjective social functioning, energy, motor function, and vigilance. CONCLUSIONS: We found a relatively high QoL, a low rate of subjective impairment, but a high incidence of objective executive deficits in untreated elderly patients with new-onset epilepsy. Neurological status and body mass index, rather than seizure frequency or severity, were risk factors for cognitive impairment. Given the relevance of cognition in the course of epilepsy and its treatment, routine screening before treatment initiation is highly recommended.

Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups.

BACKGROUND AND PURPOSE: In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed. METHODS: Age at surgery and duration of epilepsy, which was differentiated according to histopathology (AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately. RESULTS: Of all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7 years and the duration of epilepsy until surgery increased by 5 years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery. CONCLUSIONS: During the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS (mTLE + AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease-modifying factors which have changed the incidence of classical mTLE + AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery.

Disentangling the relationship between epilepsy and its behavioral comorbidities - the need for prospective studies in new-onset epilepsies.

It has been long recognized that there is more to epilepsy than seizures. The prevalence of such neurobehavioral abnormalities as cognitive and mood disorders, autism spectrum disorder, and attention deficit and hyperactivity disorder (ADHD) is significantly higher among patients with epilepsy than in the general population. A long-held view that comorbidities of epilepsy represent mere epiphenomena of seizures has undergone substantial transformation during the past decade, as emerging clinical evidence and experimental evidence suggest the involvement of specific neurobiological mechanisms in the evolution of neurobehavioral deficits in patients with epilepsy. Developmental aspects of both epilepsy and its comorbidities, as well as the frequently reported reciprocal connection between these disorders, both add other dimensions to the already complex problem. In light of progress in effective seizure management in many patients with epilepsy, the importance of neurobehavioral comorbidities has become acute, as the latter are frequently more detrimental to patients' quality of life compared with seizures. This calls for a serious increase in efforts to effectively predict, manage, and ideally cure these comorbidities. Coordinated multicenter clinical, translational, and basic research studies focusing on epidemiology, neuropsychology, neurophysiology, imaging, genetics, epigenetics, and pharmacology of neurobehavioral comorbidities of epilepsy are absolutely instrumental for ensuring tangible progress in the field. Clinical research should focus more on new-onset epilepsy and put particular emphasis on longitudinal studies in large cohorts of patients and groups at risk, while translational research should primarily focus on the development of valid preclinical systems which would allow investigating the fundamental mechanism of epilepsy comorbidities. The final goal of the described research efforts would lie in producing an armamentarium of evidence-based diagnostic tools and therapeutic interventions which would at minimum mitigate and at maximum prevent or abolish neurobehavioral comorbidities of epilepsy and, thus, improve the quality of life of those patients with epilepsy who suffer from the said comorbidities.

[Assessing activities of daily living in patients with epilepsy]. / Die Erfassung von Aktivitäten des täglichen Lebens (ADL) bei Epilepsie.

BACKGROUND: Objective cognitive assessment and subjective self-assessment do not sufficiently reflect actual daily routines and everyday functioning of patients with epilepsy. The study at hand examined whether a questionnaire assessing the activities of daily living provides additional diagnostic information. METHODS: A total of 180 consecutive patients with epilepsy received a questionnaire addressing (i) mood, (ii) subjective cognitive performance as well as (iii) frequencies of subjective problems in everyday life and (iv) 36 activities of daily living (ADL-Track). Normative data were based on 536 healthy volunteers. Analysis focused on the interrelation among these subjective measures as well as their relation to objective neuropsychological performance. RESULTS: Compared to the normative sample, social activities, home activities, and mobility were reduced in 25 - 34 % of the patients (OR = 2.07 - 2.79). Frequencies of activities of daily living reflect the results of subjective performance ratings ("attention", "praxia") and objective performance in attention, language, intelligence and memory. A negative mood showed highly significant correlations with subjective complaints and increased the risk of reduced activities by a factor of 2 - 3. Multiple regression analyses explained between 9 - 22 % of the variance of the ADL-Track scales. CONCLUSION: The ADL-Track, a questionnaire on frequencies of activities of daily living, appears more independent from mood than subjective complaints and it shows relevant correlations with subjective and even more with objective cognitive measures. Moreover, it indicates a behavioural domain in epilepsy which is not yet covered by standard diagnostics. When applied longitudinally, the ADL-Track may well turn out to be a valuable longer-term outcome parameter with regard to epilepsy and its treatment.

Neuropsychological course of voltage-gated potassium channel and glutamic acid decarboxylase antibody related limbic encephalitis.

BACKGROUND AND PURPOSE: Autoantibodies (abs) to glutamic acid decarboxylase (GAD) and to voltage-gated potassium channels (VGKC) induce distinct courses of limbic encephalitis, related to MRI findings, seizure outcome and cognition. METHODS: A detailed analysis of the cognitive course of the two forms is presented, spanning a median time interval of 28 months, including parameters of attention, learning and memory in 15 VGKC-ab-positive and 16 GAD-ab-positive patients. RESULTS: In both groups, the initially significantly impaired attention performance recovered to a putatively premorbid level. In VGKC patients the partially severely impaired learning and memory performance improved under treatment but remained subnormal at last follow-up. By contrast, GAD-ab-positive patients had initially less impaired learning and memory scores but did not show an improvement under treatment. CONCLUSIONS: The results provide evidence of distinct relations between inductive processes and cognitive outcome in VGKC-ab-positive and GAD-ab-positive subforms of limbic encephalitis, which possibly depend on differences in pathogenic molecular mechanisms and affected cerebral loci.

Impaired verbal fluency under topiramate--evidence for synergistic negative effects of epilepsy, topiramate, and polytherapy.

BACKGROUND AND PURPOSE: Treatment with topiramate (TPM) is known to negatively affect executive functions and verbal fluency in particular. However, judgments of cognitive side effects under TPM rarely consider clinical conditions and possible effects of epilepsy, treatment, and drug load. METHODS: This retrospective cross-sectional study in large cohorts of patients with epilepsy evaluated the impact of TPM mono- and polytherapy on verbal fluency. To isolate TPM-induced effects from those of epilepsy and antiepileptic medication in general, verbal fluency under TPM (N = 421) was compared to the performance of a matched sample of patients with an antiepileptic medication other than TPM (N = 351), untreated patients (N = 108), and healthy controls (N = 100). RESULTS: Impaired verbal fluency performance was seen in 77% of the patients treated with TPM. Compared to healthy controls, verbal fluency in untreated patients was reduced by 22%, under monotherapy without TPM by 31% and under TPM monotherapy by 45%. With and without TPM, verbal fluency performance linearly decreased with each additional drug in polytherapy. On each level, performance under TPM was 21-28% worse than in the respective condition without TPM. Unimpaired performance under TPM was primarily associated with lower dose, higher education, and a later onset of epilepsy. CONCLUSIONS: The majority of patients under TPM shows reduced verbal fluency. However, when taking the cumulative negative effects of epilepsy, and the concomitant drug regimen into account, TPM is associated with a 21-28% poorer performance as compared with other drugs. Additionally, the data indicate an impact of dose and reserve capacity on the occurrence of impairments.

Introduction and first validation of EpiTrack Junior, a screening tool for the assessment of cognitive side effects of antiepileptic medication on attention and executive functions in children and adolescents with epilepsy.

OBJECTIVE: Maximum seizure control, preservation of cognition, and prevention of developmental hindrance are major aims of the pharmacological treatment of children and adolescents with epilepsy. Herewith we introduce the junior version of EpiTrack, a 12- to 15-minute screening test for monitoring the cognitive effects of antiepileptic drug treatment in children and adolescents aged 6 to 18. METHODS: The test, which comprises six subtests (Speed, Flexibility, Planning, Response Inhibition, Word Fluency, Working Memory), was administered to 277 children and adolescents aged 6-18 years, 111 of whom were retested after an interval of 3 months. For the first clinical validation, 155 patients (46% idiopathic/benign, 62% seizure free) were evaluated. RESULTS: Standardization and correction for age resulted in a mean score of 33 ± 2 points, which was no longer correlated with age (r=0.005). The retest practice effect was 0.7 ± 2 points, and the reliability r(tt)=0.78. Factor analysis indicated one executive factor in controls and patients. In the epilepsy group, 50% of the patients were impaired (controls 14%). Number of antiepileptic drugs, use/no use of individual drugs, type of epilepsy, earlier age at onset, generalized tonic-clonic seizures, and history of febrile seizures made a difference in test performance. For patients and controls, EpiTrack scores reflected parents' performance ratings and the children's needs for extra education. CONCLUSION: The junior version of EpiTrack appears to be a valid and reliable screening tool for the assessment of executive functions in children and adolescents. Future studies with a repeated measurement design must show how well this tool is suited for the tracking of cognitive effects of antiepileptic drug treatment.