Cognitive function after concurrent temozolomide-based chemoradiation therapy in low-grade gliomas.

PURPOSE: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG). MATERIALS/METHODS: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time. RESULTS: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination). CONCLUSION: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ.

Quality of life following concurrent temozolomide-based chemoradiation therapy or observation in low-grade glioma.

PURPOSE: Low-grade glioma (LGG) exhibits longer median survival than high-grade brain tumors, and thus impact of our therapies on patient quality of life remains a crucial consideration. This study evaluated the effects of concurrent temozolomide-based chemoradiation (RT + TMZ) or observation on quality of life (QOL) in patients with low-grade glioma. METHODS: We completed a retrospective cross-sectional study of adults with LGG who underwent surgery with known molecular classification from 1980 to 2018. Postoperatively, patients were either observed or received adjuvant concurrent temozolomide-based chemoradiation. EQ-5D and PHQ-9 depression screen were completed before outpatient visits every 2-3 months. Baseline score was defined as ± 30 days within initial operation. RESULTS: Of the 63 patients (mean age 44 ± 17 years, 51% female) with baseline EQ-5D or PHQ-9 depression screen data and at least one follow-up measure, 30 (48%) were observed and 33 (52%) received RT + TMZ. No significant decline was seen in EQ-5D or PHQ-9 scores at 3, 6, 9, 12, and 24 months compared to baseline scores for all patients. At each time point, there was no significant difference between those who were observed or received adjuvant therapy. The linear mixed model estimating PHQ-9 value or EQ-5D index demonstrated that there was no significant difference in PHQ-9 or EQ-5D index between treatment groups (p = 0.42 and p = 0.54, respectively) or time points (p = 0.24 and p = 0.99, respectively). CONCLUSION: Our study found no significant decline in patient QOL or depression scores as assessed by patient- reported outcome measures for patients with low-grade glioma up to 2 years following surgery. We found no difference between RT + TMZ compared to observation during this time frame. Additional follow-up can help identify the longer-term impact of treatment strategy on patient experience.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

OBJECTIVES: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BACKGROUND: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. METHODS: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. RESULTS: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. CONCLUSIONS: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Implications from neurologic assessment of brain protection for total arch replacement from a randomized trial.

OBJECTIVE: The study objective was to perform a randomized trial of brain protection during total aortic arch replacement and identify the best way to assess brain injury. METHODS: From June 2003 to January 2010, 121 evaluable patients were randomized to retrograde (n = 60) or antegrade (n = 61) brain perfusion during hypothermic circulatory arrest. We assessed the sensitivity of clinical neurologic evaluation, brain imaging, and neurocognitive testing performed preoperatively and 4 to 6 months postoperatively to detect brain injury. RESULTS: A total of 29 patients (24%) experienced neurologic events. Clinical stroke was evident in 1 patient (0.8%), and visual changes were evident in 2 patients; all had brain imaging changes. A total of 14 of 95 patients (15%) undergoing both preoperative and postoperative brain imaging had evidence of new white or gray matter changes; 10 of the 14 patients had neurocognitive testing, but only 2 patients experienced decline. A total of 17 of 96 patients (18%) undergoing both preoperative and postoperative neurocognitive testing manifested declines of 2 or more reliable change indexes; of these 17, 11 had neither imaging changes nor clinical events. Thirty-day mortality was 0.8% (1/121), with no neurologic deaths and a similar prevalence of neurologic events after retrograde and antegrade brain perfusion (22/60, 37% and 15/61, 25%, respectively; P = .2). CONCLUSIONS: Although this randomized clinical trial revealed similar neurologic outcomes after retrograde or antegrade brain perfusion for total aortic arch replacement, clinical examination for postprocedural neurologic events is insensitive, brain imaging detects more events, and neurocognitive testing detects even more. Future neurologic assessments for cardiovascular procedures should include not only clinical examination but also brain imaging studies, neurocognitive testing, and long-term assessment.

Memory performance in older adults before and after temporal lobectomy for pharmacoresistant epilepsy.

Little is known about the effects of epilepsy surgery on memory in older adults. The purpose of this study was to determine if older adults exhibit greater memory decline than younger adults after anterior temporal lobectomy (ATL). Patients 55 years and older at time of surgery (23 left, 14 right ATL, range 55-66 years) were compared to patients age 25-35 years (44 left, 33 right ATL) to assess differences in preoperative to postoperative change in WMS-III index scores. Repeated-measures ANOVAs and ANCOVAs revealed that older patients did not demonstrate greater decline than younger patients across any of the memory indices. Rather, in the left ATL group, older patients showed less decline than younger patients on the Auditory Delayed Memory Index. Similarly, in the right ATL group, older patients showed less decline than younger patients on the Visual Delayed Memory Index. These patterns were also apparent in frequency of individual change. Results provide preliminary evidence that older adults who are good candidates for ATL are not at greater risk for memory decline when measured at 7 months postoperatively.

Word-finding difficulties confound performance on verbal cognitive measures in adults with intractable left temporal lobe epilepsy.

This study sought to determine if word-finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi-square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42-46%) as compared to patients with fewer WFDs (18-24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word-retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection.

Working memory and intelligence are associated with victoria symptom validity test hard item performance in patients with intractable epilepsy.

Loring et al. (Journal of clinical and experimental neuropsychology, 2005:27;610­617) observed relationships between VSVT hard item performance and IQ and memory indices in epilepsy surgical candidates, with a potential confound of low FSIQ on VSVT performance. The present study replicated the Loring et al. study in a larger sample and extended their findings by examining the relationships among VSVT performance, FSIQ, and working memory. A total of 404 patients with medically intractable epilepsy completed a comprehensive neuropsychological assessment. Differences in WAIS-III and WMS-III performance were examined as a function of VSVT hard score categories as determined by Grote et al. (2000)--that is, valid, > 20/24; questionable, 18­20; or invalid, < 18. Quantile regression models were constructed to compare the strength of the relationship between FSIQ and VSVT at various points of the FSIQ distribution. Linear regression analyses examined working memory as a potential mediator between FSIQ and VSVT performance. The invalid group performed more poorly than the valid and questionable groups on multiple measures of intelligence and memory. The strength of the relationship between FSIQ and VSVT hard item performance decreased as FSIQ increased, and working memory mediated this relationship. Results suggest VSVT hard item scores may be impacted by working memory difficulties and/or low intellectual functioning.

Computerized neuropsychological assessment devices: joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology.

This joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology sets forth our position on appropriate standards and conventions for computerized neuropsychological assessment devices (CNADs). In this paper, we first define CNADs and distinguish them from examiner-administered neuropsychological instruments. We then set forth position statements on eight key issues relevant to the development and use of CNADs in the healthcare setting. These statements address (a) device marketing and performance claims made by developers of CNADs; (b) issues involved in appropriate end-users for administration and interpretation of CNADs; (c) technical (hardware/software/firmware) issues; (d) privacy, data security, identity verification, and testing environment; (e) psychometric development issues, especially reliability, and validity; (f) cultural, experiential, and disability factors affecting examinee interaction with CNADs; (g) use of computerized testing and reporting services; and (h) the need for checks on response validity and effort in the CNAD environment. This paper is intended to provide guidance for test developers and users of CNADs that will promote accurate and appropriate use of computerized tests in a way that maximizes clinical utility and minimizes risks of misuse. The positions taken in this paper are put forth with an eye toward balancing the need to make validated CNADs accessible to otherwise underserved patients with the need to ensure that such tests are developed and utilized competently, appropriately, and with due concern for patient welfare and quality of care.

Computerized neuropsychological assessment devices: joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology.

This joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology sets forth our position on appropriate standards and conventions for computerized neuropsychological assessment devices (CNADs). In this paper, we first define CNADs and distinguish them from examiner-administered neuropsychological instruments. We then set forth position statements on eight key issues relevant to the development and use of CNADs in the healthcare setting. These statements address (a) device marketing and performance claims made by developers of CNADs; (b) issues involved in appropriate end-users for administration and interpretation of CNADs; (c) technical (hardware/software/firmware) issues; (d) privacy, data security, identity verification, and testing environment; (e) psychometric development issues, especially reliability and validity; (f) cultural, experiential, and disability factors affecting examinee interaction with CNADs; (g) use of computerized testing and reporting services; and (h) the need for checks on response validity and effort in the CNAD environment. This paper is intended to provide guidance for test developers and users of CNADs that will promote accurate and appropriate use of computerized tests in a way that maximizes clinical utility and minimizes risks of misuse. The positions taken in this paper are put forth with an eye toward balancing the need to make validated CNADs accessible to otherwise underserved patients with the need to ensure that such tests are developed and utilized competently, appropriately, and with due concern for patient welfare and quality of care.

Pre-surgical mood predicts memory decline after anterior temporal lobe resection for epilepsy.

This study examined pre-surgical depressed mood as a predictor of post-surgical memory change in adults who underwent temporal lobe resections (TLRs; n = 211). Patients completed the Wechsler Memory Scale-III and Beck Depression Inventory-Second Edition (BDI-II) before and after TLR (left = 110, right = 101) and were divided into two groups (clinically elevated depressive symptoms or not depressed) based on BDI-II score. Left-TLR patients with poorer pre-surgical mood had greater verbal memory declines after surgery compared with nondepressed left- or right-TLR patients and right-TLR patients with poor mood. Further, pre-surgical BDI-II score demonstrated incremental validity in predicting post-surgical memory change in left-TLR patients beyond pre-surgical memory scores. Differences in seizure outcome and post-surgical mood change could not account for memory decline. Results suggest that elevated pre-surgical depressive symptomatology is a risk factor for post-surgical memory decline and indicate that mood should be considered when advising patients about cognitive risks associated with temporal lobectomy. Results are discussed in terms of poor pre-surgical mood as an indicator of reduced cognitive reserve.

The Family Pictures subtest of the WMS-III: relationship to verbal and visual memory following temporal lobectomy for intractable epilepsy.

This study examined the extent to which the Family Pictures (FP) subtest of the Wechsler Memory Scale-Third Edition (WMS-III) is related to verbal memory measures and right mesial temporal integrity. Epilepsy patients who underwent temporal lobectomy did not differ in the extent to which FP scores changed from before to after surgery, although postoperative FP performance was worse in those who underwent right temporal lobectomy than in those who underwent left temporal lobectomy. FP was most strongly related to the Logical Memory subtest from the WMS-III. Results suggest that FP measures both verbal and visual memory and is minimally sensitive to lateralization of temporal lobectomy.

Poor presurgical performance on both verbal and visual memory measures is associated with low risk for memory decline following left temporal lobectomy for intractable epilepsy.

Studies have shown a lower risk for verbal memory decline following dominant anterior temporal lobectomy (ATL) among patients with poor, presurgical verbal memory scores. It is unclear however, if the risk of decline is increased in patients who also have reduced visual memory. Objective and subjective memory outcome following left ATL was examined in twelve patients with reduced presurgical visual and verbal memory scores. Only one patient demonstrated a meaningful decline in memory scores, with a decline in visual memory following surgery. Presurgically, this patient demonstrated poor memory bilaterally on Wada testing and small discrepancy in hippocampal volumes. She was also one of two patients who continued to have seizures post-surgery. This preliminary study suggests that patients with unilateral, left TLE and poor verbal and visual memory are unlikely to show meaningful memory declines following left ATL, particularly if they demonstrate expected patterns on Wada testing, hippocampal volume discrepancy (left < right), and postsurgical seizure-freedom.

APOE epsilon4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy.

This study examined the relationship between the APOE epsilon4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one epsilon4 allele (n=22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without epsilon4 (43%). These preliminary results demonstrate that APOE epsilon4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms.

Relationship between presurgical memory performance on the Wechsler Memory Scale-III and memory change following temporal resection for treatment of intractable epilepsy.

Previous research demonstrated a relationship between preoperative memory measured by the Wechsler Memory Scale-Revised (WMS-R) and postsurgical memory change in patients who underwent left (LATL), but not right (RATL) anterior temporal lobectomy. The current study replicated previous efforts using the Wechsler Memory Scale-Third Edition (WMS-III) in a larger sample. The WMS-III was administered to 161 patients with medically intractable epilepsy prior to and approximately 6 months following LATL or RATL. Correlations between presurgical memory on WMS-III indices and memory change following surgery were calculated for each group. Significant negative relationships were found between pre- and postsurgical memory scores in patients who underwent LATL on all WMS-III measures (r=-0.31 to -0.43). Significant negative correlations were observed in patients who underwent RATL only on visual memory measures (r=-0.24 to -0.44). Findings support previous conclusions using the WMS-R showing that patients who undergo LATL with higher presurgical memory ability are at greater risk for memory decline following temporal resection than patients with lower presurgical memory scores.

Temporal lobe neoplasm and seizures: how deep does the story go?

[March 2008-Cleveland Case Report]. There is a well-described association between the occurrence of developmental tumors and the presence of cortical dysplasia in the neighboring brain tissue. The main surgical approaches in the treatment of medically refractory epilepsy related to such developmental tumors include a lesionectomy versus a tailored cortical resection, often guided by an invasive evaluation. This case report describes the surgical management of a 26-year-old female with olfactory auras evolving into automotor seizures and convulsions, occurring in the context of a right temporo-parietal developmental lesion. It illustrates the pros and cons of various surgical approaches, and discusses some pathophysiological aspects of developmental tumors, dysplasia and epilepsy. [Published with video sequences].

Relationships among victoria symptom validity test indices and personality assessment inventory validity scales in a large clinical sample.

The purpose of this study was twofold: (1) to examine the relationships among measures of cognitive symptom exaggeration (i.e., response accuracy and response latency) and (2) to examine the relationship between measures of cognitive and psychopathological symptom exaggeration. It was expected that Victoria Symptom Validity Test (VSVT) accuracy and latency measures would be significantly correlated, with invalid responders demonstrating longer response latencies. VSVT scores were also expected to correlate significantly with the Negative Impression Management (NIM) and Infrequency (INF) subscales of the Personality Assessment Inventory (PAI). VSVT and PAI data were collected from 300 patients during routine clinical neuropsychological evaluations. Results indicated that VSVT accuracy and latency measures were significantly and moderately correlated, and both types of VSVT scores were significantly, but modestly, related to NIM, but not INF. These findings suggest that VSVT response latencies may supplement accuracy scores in identifying patients who are exerting suboptimal effort on cognitive measures. These findings further suggest that measures of cognitive symptom validity only partially overlap with measures of psychopathological symptom exaggeration.