Sallie Baxendale

Effects of topiramate on cognitive function

OBJECTIVE To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p<0.001). Improvements in verbal fluency (p<0.05), verbal learning (p<0.01), and digit span (p<0.001) were recorded in those patients who had topiramate withdrawn or reduced. CONCLUSIONS In our patient group topiramate had a negative impact on cognition which was consistent with subjective complaints of patients. Tests requiring verbal processing seemed especially sensitive to the drug. A decline in verbal intellect (VIQ), a measure which has been considered by some to be insensitive to antiepileptic drug effects, was particularly striking. Caution is warranted in the interpretation of the findings due to methodological limitations of the study design. Further investigation of mediating factors such as serum concentrations, comedication, and other potential risk factors, however, is needed to enable appropriate targeting of treatment with this effective antiepileptic agent.

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach.

Predicting Memory Decline Following Epilepsy Surgery: A Multivariate Approach

Summary:  Background: While some patients experience a decline in memory function following an anterior temporal lobe resection, there is considerable individual variation in the extent, nature, and direction of postoperative memory change. Patients with surgically remediable temporal lobe epilepsy differ in etiology, the extent and type of underlying pathology, and on demographic and epilepsy‐related variables, all of which may have an impact on their pre‐ and postoperative neuropsychological functioning. This study examined the relationship between these variables and postoperative memory decline.

The role of the Wada test in the surgical treatment of temporal lobe epilepsy: An international survey

The Wada test, (intraarterial amobarbital procedure, IAP) has been used to determine language dominance and assess the risk of a postoperative amnesic syndrome in temporal lobe epilepsy (TLE) surgery candidates since its inception in the mid twentieth century (Wada J, 1949). In 1993, over 95% of epilepsy surgery centers worldwide reported using the IAP, with 85% conducting the procedure on all surgical candidates, primarily to assess language dominance and memory capacity (Rausch et al., 1993). Scores from the IAP were subsequently used as an adjunct in lateralizing the seizure focus (Davies et al., 1999; Kanemoto et al., 1999; Swearer et al., 1999; Alpherts et al., 2000; Akanuma et al., 2003) and to predict changes in postoperative memory function (Bell et al., 2000; Chiaravalloti & Glosser, 2001; Sabsevitz et al., 2001; Stroup et al., 2003; Lacruz et al., 2004; Lee et al., 2005; Andelman et al., 2006). However, the IAP is an invasive procedure with small, but serious risks of significant morbidity (Rausch et al., 1993; Loddenkemper et al., 2002). Morbidity risks are increased in selective procedures. Procedural failures, including somnolence can invalidate test scores and the accurate assessment of memory function can be difficult following perfusion of the language dominant hemisphere or perfusion of anterior regions leading to perseverative responses and/or behavioral disinhibition (Baxendale et al., 1996; Hamer et al., 2000; Masia et al., 2000; Bengner et al., 2003; de Paola et al., 2004). Topiramate, an antiepileptic drug, may also interfere with the validity of the procedure (McCabe & Eslinger, 2000; Kipervasser et al., 2004). Adverse reactions may be more common in procedures employing newer compounds such as etomidate, propofol, or brevital rather than amobarbital (Grote & Meador, 2005; Mikuni et al., 2005). High-definition structural MRIs enable the detailed examination of ipsilateral and contralateral structures in presurgical candidates (Duncan, 2007). Some centers now use data from these images, combined with detailed baseline neuropsychological assessments to assess the structure and the functional capacity of the contralateral mesial temporal lobe in surgical candidates, in order to assess the risk of a postoperative amnesic syndrome and to predict postoperative changes in memory function (Stroup et al., 2003; Baxendale et al., 2006). Functional imaging paradigms are also beginning to show promise in this regard (Richardson et al., 2004; Janszky et al., 2005). The potential of functional MRI (fMRI) to lateralize language functions prior to epilepsy surgery is becoming established. Large series of patients have undergone language evaluation with both IAP and fMRI and the latter is rapidly making the transition from an experimental technique to a clinical tool (Baxendale, 2002; Powell & Duncan, 2005). In the light of these developments and increasing divergence in the literature regarding the future role of the IAP and its counterparts in the presurgical evaluation of TLE candidates (van Emde, 1999; Valton & Mascott, 2004; Grote & Meador, 2005; Jones-Gotman et al., 2005), we initiated an international survey of current practice to determine the prevalence and rationale behind the employment of the IAP in the presurgical evaluation of TLE patients across the world at the present time.

Amnesia in temporal lobectomy patients: Historical perspective and review

Profound memory loss is a rare but serious complication of temporal-lobe surgery for the relief of medically intractable epilepsy. This paper examines the characteristics of the patients who have been reported to become amnesic following temporal-lobe surgery over the last four decades. The critical role of the hippocampi in memory function are implicated in autopsy studies and MRI investigations, but these cases suggest that a range of memory impairments result from bilateral hippocampal damage, rather than a pure amnesic syndrome in every case. There is some evidence that bilateral structural hippocampal abnormalities may not necessarily be associated with significant memory problems, if these abnormalities have a developmental basis. However, whilst not necessarily profound, any post-operative deterioration in memory function remains a significant consideration in the presurgical evaluation of temporal-lobe epilepsy patients.

Improvements in memory function following anterior temporal lobe resection for epilepsy

Background: While up to a third of patients may experience a decline in memory following an anterior temporal lobe resection (ATL) for epilepsy, between 10 and 20% may experience a postoperative improvement in function. The aim of this study was to examine the preoperative characteristics of these patients. Methods: Logistic regression analyses were used to determine which variables influenced postoperative memory improvement following ATL on standardized memory tests in 237 patients with unilateral hippocampal sclerosis (105 right; 132 left). Results: A total of 22% of the right ATL and 9% of the left ATL group demonstrated a significant postoperative improvement in verbal learning. A total of 9% of the right ATL and 16% of the left ATL group demonstrated a significant postoperative improvement in visual learning. In the R ATL group, postoperative improvements in verbal learning were associated with poor preoperative verbal learning, a shorter duration of epilepsy, higher scores on the visual learning task, and an older age at the time of surgery. In the L ATL group, postoperative improvements in visual learning were associated with poor preoperative visual learning, a shorter duration of epilepsy, and a higher IQ. Postoperative improvements in memory functions associated with the ipsilateral temporal lobe were not associated with demographic or epilepsy-related variables. Conclusions: Memory deficits normally associated with the function of the contralateral temporal lobe in patients with unilateral hippocampal sclerosis may improve postoperatively in patients with a shorter duration of epilepsy and the cognitive capacity to develop compensatory strategies.

Remote Memory in Epilepsy

Summary: Purpose: There is now a considerable amount of research relating to memory functioning in epilepsy. The majority of studies have focused on the retention of new information, and few reports have measured memory for past events. This study aims to redress this and measure the efficiency of remote memory in epilepsy.

The Role of Functional MRI in the Presurgical Investigation of Temporal Lobe Epilepsy Patients: A Clinical Perspective and Review

Speculation regarding the role that fMRI might play in the presurgical assessment of temporal lobe epilepsy patients began almost as soon as the technology was introduced. Much of this speculation centred on hopes that fMRI might eventually supersede the invasive intracarotid amobarbital procedure (IAP). This review examines the progress that has been made to date towards this aim. A decade after its inception, fMRI paradigms that reliably lateralize language dominance have been established. However, fMRI has yet to achieve its full potential in the mapping of clinically relevant language skills in presurgical epilepsy patients. The role of fMRI in the assessment of postoperative amnesic risk is more complex. The results from recent fMRI memory studies in people with epilepsy have been encouraging. However, as yet, fMRI techniques cannot be used alone to confidently assess the risk of a postsurgical amnesic syndrome. It seems probable that these techniques will continue to be combined with traditional neuropsychological assessment and information from structural MRI studies and the other presurgical investigations to assess postoperative amnesic risk.

Beyond localization: The role of traditional neuropsychological tests in an age of imaging

Rapid advances in structural and functional magnetic resonance imaging (MRI) present two significant challenges to the rationale and role of the traditional neuropsychological assessment in the presurgical evaluation of epilepsy surgery candidates today. The first is a direct challenge to the model of material‐specific memory that has underpinned much clinical practice over the last 50 years. The second, more fundamental, challenge goes to the very heart of the lateralizing/localizing approach that has been the cornerstone of clinical neuropsychology practice in epilepsy surgery centers to date. This review examines these challenges and suggests some ways in which the profession might respond and adapt. We conclude that noninvasive neuropsychological assessment remains a critical investigation in the presurgical evaluation of epilepsy surgery patients. Its value stretches beyond the localization of a surgically remediable seizure focus. Once a vital test, other investigations are now superior in this respect in many cases. However, new technologies have enhanced the role of the traditional neuropsychological assessment, which is now able to provide unparalleled insights and predictions into the way in which the underlying pathology, seizures, and proposed surgery shape an individual’s profile of cognitive abilities. Detailed neuropsychological feedback enables the patient to make an informed decision, and forms the basis of the tailor made preemptive rehabilitation programs that can be implemented preoperatively, minimizing the most significant morbidity associated with epilepsy surgery today.

Cognitive consequences of childhood-onset temporal lobe epilepsy across the adult lifespan.

Objectives: To examine the influence of side of pathology and gender on changes in cognitive function across the adult lifespan in a homogenous sample of patients with mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS). Methods: We retrospectively examined the neuropsychological profiles of 382 patients in 3 cohorts: cohort 1 aged 18–30 (n = 171), cohort 2 aged 31–45 (n = 170), and cohort 3 aged 46–65 (n = 41). All participants had medically intractable seizures associated with unilateral HS and an onset of epilepsy in childhood, with an average onset at 7 years. Results: There were no significant differences between the age cohorts on the measures of intellect, language, or memory. Duration of epilepsy (years) was not related to IQ, memory, or language scores in any group. Male subjects performed better than female subjects on verbal IQ, performance IQ, and naming tasks. Verbal learning and recall scores were worse in those with left than right HS. Conclusions: Our findings suggest that the profile of cognitive deficits associated with MTLE is already established as children with temporal lobe epilepsy enter adulthood. While memory and language skills are maximally affected, intellectual function is also compromised in MTLE. This profile appears to remain stable across the adult lifespan, at least until 60 years of age, despite the intractable nature of the seizures. Side of pathology and gender are significant mediating factors in shaping the profile of cognitive deficits associated with childhood-onset MTLE, with people with left-sided HS and female subjects particularly vulnerable to more widespread cognitive dysfunction.