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.

[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.

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.

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.

[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.

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.

[Neuropsychology in epilepsy]. / Neuropsychologie bei Epilepsie.

Neuropsychological assessment has become an essential tool for the diagnosis and outcome control in the clinical management of epilepsy. However, only a few attempts have been made to formulate explicit guidelines about which cognitive domains should be addressed in epilepsy patients and which of the various coexisting neuropsychological tests would provide an appropriate and evidence-based assessment. The present survey among 14 epilepsy centres in German-speaking countries indicates that there is at least some consensus concerning the cognitive domains which need to be addressed. However, concerning test selection a large diversity of more than 200 applied psychometric tests among the different epilepsy centres becomes evident. Evidence-based test selection was only seen in 25 % of the applied instruments. One-third of the tests are conducted because of pragmatic reasons or due to subjective preferences, whereas for the majority of tests no justification is provided. Taking into consideration the bulk of publications on cognition and epilepsy, it is time to establish an evidence-based core test battery for the use in epilepsy patients. Therefore a closer communication between centres is needed to come to an agreement and to accumulate experience with already established and newly developed tests in order to promote evidence-based neuropsychology in the field of epilepsy.

[Neuropsychology in epilepsy]. / Neuropsychologie bei Epilepsie.

In order to understand cognitive impairment associated with epilepsy, it is essential to appreciate that independent static and dynamic factors affect brain function in this disease. Whereas morphological lesions or structural changes are associated with more or less irreversible deficits, epileptic activity, seizures, and the treatment of epilepsy can cause dynamic and principally reversible impairment. The relative contribution of these factors differs depending on the type of epilepsy, the age at lesion/epilepsy onset, the localization and lateralization of epilepsy and individual demographic patient characteristics. Altered brain structure and function can result in epilepsy, but epilepsy can also alter the functional cerebral organization of the brain. Thus epilepsy-related cognitive impairment must be integrated within a developmental neuropsychological framework. The aetiology of epilepsy is strongly related to the age of onset. From a neuropsychological point of view, it makes a big difference for cognitive outcome as to whether epilepsy hits the maturing versus mature or aging brain. Dependent on this, epilepsy can result in retardation, loss of acquired functions, or accelerated mental decline. It will be demonstrated that cognitive impairments in epilepsy mostly exist from the beginning of epilepsy, that early onset lesions/epilepsy interfere with mental development, and that a progressive aetiology, severe seizures, and lesions secondary to epilepsy may accelerate mental decline. It will furthermore be discussed that uncontrolled epilepsy and epileptic activity may reversibly and irreversibly contribute to cognitive impairment. The same is demonstrated with regard to the pharmacological treatment of epilepsy. Finally, the cognitive risks and benefits of epilepsy surgery and the advantages of selective surgery will be addressed. The consequences for the neuropsychological assessment are discussed in part two of this review.

Thinking of boards as families.

As hospitals forge new strategic partnerships, the question of "what to do about the board" is always prominent. But before hospital boards can look at governance roles, composition, and structure in integrated mechanisms, many need to take a hard look at themselves, writes long-time board observer John Witt. In this perspective, he argues that many boards act like dysfunctional families: They appear normal and even successful until a crisis occurs to reveal underlying malfunctions. Both families and boards can help themselves by working on who they function as a group, he says.

Board training policies and practices.

This survey reveals some very interesting aspects about training of hospital boards of directors. When both CEOs and board chairpersons agree that making board training mandatory is necessary today, it is probably worthy of some serious board discussion.