Marijke Miatton

Vagus nerve stimulation…25 years later! What do we know about the effects on cognition?

VNS therapy was delivered to patients for the first time in 1988. After 25 years, insight in the antiepileptic and antidepressant mechanism of action of VNS has grown steadily. The effects on cognition and especially memory remain controversial. This review provides an elaborate overview of studies addressing cognition and describes potential underlying mechanisms for the reported effects. Short-term VNS has an effect on verbal memory recognition when administered at the correct timing and dosage. Chronic VNS resulted into a positive effect on the cognitive status in an Alzheimer population. Positive effect of chronic VNS in epilepsy or depression patients on global cognitive functioning are less convincing. Neither do the results reveal a negative effect which has major implications for chronic treatment of neurology patients. A cascade of neurochemical processes put in motion by changes in NE concentrations in reaction to stimulation of the vagal nerve may underlie the VNS-induced effects on cognition and memory. In Alzheimer pathology, NE may act as an anti-inflammatory agent on brainstem nuclei.

A decade of experience with deep brain stimulation for patients with refractory medial temporal lobe epilepsy

In this study, we present long-term results from patients with medial temporal lobe (MTL) epilepsy treated with deep brain stimulation (DBS). Since 2001, 11 patients (8M) with refractory MTL epilepsy underwent MTL DBS. When unilateral DBS failed to decrease seizures by > 90%, a switch to bilateral MTL DBS was proposed. After a mean follow-up of 8.5 years (range: 67-120 months), 6/11 patients had a ≥ 90% seizure frequency reduction with 3/6 seizure-free for > 3 years; three patients had a 40%-70% reduction and two had a < 30% reduction. In 3/5 patients switching to bilateral DBS further improved outcome. Uni- or bilateral MTL DBS did not affect neuropsychological functioning. This open study with an extended long-term follow-up demonstrates maintained efficacy of DBS for MTL epilepsy. In more than half of the patients, a seizure frequency reduction of at least 90% was reached. Bilateral MTL DBS may herald superior efficacy in unilateral MTL epilepsy.

Neurocognitive Consequences of Surgically Corrected Congenital Heart Defects: A Review

With advances in surgical procedures, neuropsychological assessment after congenital heart defects and pre, peri- and/or postoperative predictors of adverse outcome has become an important focus in research. We aim to summarize neuropsychological sequelae associated with different types of congenital heart defects, critically review the methodology used in more than 20 empirical studies that were retrieved from biomedical electronic search engines, and identify possible directions for future research. Despite the lack of adequate control groups and long-term studies, there seem to be some cognitive deficits. The largest group of children with isolated congenital heart defects present with normal intellectual capacities. However, they tend to show language deficits and motor dysfunction. Although performances on memory tasks are good, unambiguous conclusions concerning their attentional and executive functioning are still lacking. Serious behavioral problems are not an issue. In addition to a detailed description of the (neuro) psychological consequences of pediatric cardiac surgery, an overview of the predictors of the cognitive defects is provided.

Predictors of cognitive impairment in advanced Parkinson’s disease

Objective: To investigate the cognitive profile of patients with idiopathic Parkinson’s disease and to determine the demographic and medical variables that contribute to the cognitive outcome. Design: Retrospective cohort analysis. Methods: 100 patients with idiopathic Parkinson’s disease were given a neuropsychological test battery investigating attention, memory, and visuospatial and executive functions. Test performance was compared against normative data, and linear regression determined significant predictors of cognitive impairment from a set of demographic and disease course variables. Results: Frontal-type cognitive dysfunction was widespread in patients with advanced Parkinson’s disease. Attention and memory were mildly to moderately impaired, whereas visuospatial function showed only subtle impairment. Older age and tremor at onset were significant predictors of poor cognitive performance. Conclusions: The observed cognitive impairment in patients with advanced Parkinson’s disease is more than expected for normal aging. Although in apparent contrast with most previous research, reporting a greater risk of cognitive dysfunction in Parkinson’s disease patients with predominant akinesia/rigidity, tremor at onset may be a marker for more widespread brain pathology that contributes to an increased risk of cognitive impairment.

Behavior and self-perception in children with a surgically corrected congenital heart disease.

Objective: We sought to combine parental and child reports in order to describe the behavior, self-perception, and emotional profile of children with a surgically corrected congenital heart disease (CHD). Methods: Forty-three children with a surgically corrected CHD were selected and compared to an age- and sex-matched healthy group. The parents of the CHD children completed a behavior rating scale, the Child Behavior Checklist. Children 8 years and older (n = 23) completed a self-report questionnaire concerning perceived competence, their anxiety level, and feelings of depression. Results: Compared to parents of healthy children, those of CHD children report significantly lower school results (p < .01), more school problems in general (p < .01), and a higher percentage of their children repeated a school year (p < .01). They also reported more social (p < .01) and attention problems (p < .01) and more aggressive behavior (p < .05). On self-perception and state anxiety questionnaires, no significant differences were found between the patient group and the healthy group. On a depression scale, however, children with a surgically corrected CHD reported more depressive feelings than healthy controls (p < .01). Conclusion: Parents of children with CHD rate their childs school competence to be weaker than healthy peers, they report more attention and social problems and more aggressive behavior. Children themselves did not report differences on perceived competence or anxiety but they do indicate more depressive symptoms than healthy peers.

The cognitive effects of amygdalohippocampal deep brain stimulation in patients with temporal lobe epilepsy

The aim of this study was to examine the effects of amygdalohippocampal deep brain stimulation (AH-DBS) on cognitive functioning in patients with refractory temporal lobe epilepsy. The population consisted of 10 patients (7 men) who underwent ipsilateral (n=8) or bilateral (n=2) AH-DBS. Intellectual and neuropsychological evaluation was performed before and 6 months after initiation of AH-DBS. Group analyses revealed no overall pattern of change in cognitive measures, but improvement was seen in emotional well-being. Individual results varied over a broad spectrum ranging from no cognitive effects to negative effects on intelligence capacities, divided attention, and concept formation, to positive effects on speed of information processing and speed of finger movements. AH-DBS is a valuable treatment alternative for patients with refractory epilepsy that appears to have no major adverse neuropsychological consequences and enhances emotional well-being on the group level. Individual results are too diverse at this moment to allow viable interpretation. Additional studies are needed to confirm these preliminary results.

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: The limits of material specificity

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.

Clinical relevance of memory performance during Wada is stimulus type dependent

Objectives: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). Methods: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. Results: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. Conclusions: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty‐six epilepsy centers and members of “E‐PILEPSY” (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co‐normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Neurocognitive development and behaviour in school-aged children after surgery for univentricular or biventricular congenital heart disease

OBJECTIVES To assess the long-term neuropsychological and behavioural profile of school-aged children who were treated for univentricular heart (UVH) conditions or biventricular heart defect (BiVH) in infancy in a cross-sectional study design. METHODS Sixty-three patients, 17 UVH (13 males, 4 females) and 46 BiVH (19 males, 27 females), were assessed at a mean age of 9.1 years (2.2 years) with an intelligence and neuropsychological test battery. Results were compared between subgroups (UVH, BiVH and a healthy control group). Associations between cognitive outcome, medical and socio-demographic factors were explored. Parents completed the Child Behavior Checklist (CBCL). RESULTS Mean intelligence and neuropsychological scores were found within normal ranges for all diagnostic groups. Significant differences between UVH patients and controls emerged on auditory sustained and alternating attention, fine motor skills, visuospatial information processing, and to a lesser extent, memory performance. Parents of UVH patients reported more externalizing problems and school problems. Patient groups did not differ on neuropsychological outcome measures, nor on behavioural problems as rated by parents. CONCLUSIONS After Fontan completion, patients at school age display intelligence scores within normal population-based ranges. However, they were found at risk for subtle shortcomings in attention, fine motor skills, visuospatial information processing and externalizing behaviour problems. Considerations pertaining to neurobehavioural outcome in school-aged children are discussed.