Decreased neurite density within frontostriatal networks is associated with executive dysfunction in temporal lobe epilepsy.

OBJECTIVE: Executive dysfunction is observed in a sizable number of patients with refractory temporal lobe epilepsy (TLE). The frontostriatal network has been proposed to play a significant role in executive functioning, however, because of the complex architecture of these tracts, it is difficult to generate measures of fiber tract microstructure using standard diffusion tensor imaging. To examine the association between frontostriatal network compromise and executive dysfunction in TLE, we applied an advanced, multishell diffusion model, restriction spectrum imaging (RSI), that isolates measures of intraaxonal diffusion and may provide better estimates of fiber tract compromise in TLE. METHODS: Restriction spectrum imaging scans were obtained from 32 patients with TLE [16 right TLE (RTLE); 16 left TLE (LTLE)] and 24 healthy controls (HC). An RSI-derived measure of intraaxonal anisotropic diffusion (neurite density; ND) was calculated for the inferior frontostriatal tract (IFS) and superior frontostriatal tract (SFS) and compared between patients with TLE and HC. Spearman correlations were performed to evaluate the relationships between ND of each tract and verbal (i.e., D-KEFS Category Switching Accuracy and Color-Word Interference Inhibition/Switching) and visuomotor (Trail Making Test) set-shifting performances in patients with TLE. RESULTS: Patients with TLE demonstrated reductions in ND of the left and right IFS, but not SFS, compared with HC. Reduction in ND of left and right IFS was associated with poorer performance on verbal set-shifting in TLE. Increases in extracellular diffusion (isotropic hindered; IH) were not associated with executive dysfunction in the patient group. SIGNIFICANCE: Restriction spectrum imaging-derived ND revealed microstructural changes within the IFS in patients with TLE, which was associated with poorer executive functioning. This suggests that axonal/myelin loss to fiber networks connecting the striatum to the inferior frontal cortex is likely contributing to executive dysfunction in TLE.

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

OBJECTIVE: Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). METHODS: RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. RESULTS: Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. SIGNIFICANCE: RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy.

Stereotactic Radiosurgery for Residual and Recurrent Nonfunctioning Pituitary Adenomas: A Contemporary Case Series of GammaKnife and CyberKnife Radiosurgery.

BACKGROUND: In patients with residual or recurrent nonfunctioning pituitary adenomas (NFPAs) after transsphenoidal resection, both GammaKnife (GKRS) and CyberKnife (CKRS) stereotactic radiosurgery (SRS) are viable treatment options. OBJECTIVES: We report a retrospective single center series comparing assessing the effectiveness and complications from of these 2 commonly used SRS techniques. METHODS: A total of 53 patients with prior surgical resection and residual or recurrent NFPAs who underwent GKRS or CKRS and minimum 3-month follow-up between January 2002 and February 2017 at a single center were identified. RESULTS: A total of 34 patients underwent GKRS and 19 received CKRS. CKRS patients had a larger maximal tumor diameter (P = 0.005) and tumor volume treated (P = 0.001). Differences between GKRS and CKRS treatment parameters included target volume, target volume treated, prescribed dose, maximum dose, prescription isodose line, and conformity index (P < 0.05). The mean follow-up time was 53.74 months for GKRS and 41.48 months for CKRS patients. Tumor progression developed in 6% of cases after GKRS versus 5% after CKRS. The mean progression-free survival was 48.44 months after GKRS and 38.57 months after CKRS (P = 0.61). Five-year actuarial tumor control rates were 91% after GKRS versus 89% after CKRS (P > 0.99). There were no differences in worsened vision or rates of hypopituitarism. CONCLUSIONS: In patients undergoing single fraction GKRS versus fractionated CKRS for NFPAs, both modalities had similar rates of tumor control, new hypopituitarism, and visual morbidity despite varying indications. This study validates the versatile use of these 2 SRS modalities for patients meeting their relative criteria, especially based on proximity to the optic apparatus and normal pituitary gland.

Beyond depression: The impact of executive functioning on quality of life in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) often experience diminished quality of life (QoL). Although comorbid depression is one of the most recognized predictors of poor QoL in TLE, impairments in verbal memory (VM) and executive functioning (EF), have also been identified as risk factors, independent of other biological and psychosocial factors. In this study, we examine the contribution of depression, VM, and EF to QoL in 52 well-characterized medically-refractory TLE patients. METHODS: Quality of life was assessed with the Quality of Life in Epilepsy (QOLIE-31) questionnaire and depression symptomatology was evaluated with the Beck Depression Inventory-II (BDI-II). Tests of VM included the California Verbal Learning Test-Second Edition and the Wechsler Memory Scale-Third Edition, Logical Memory and Verbal Paired Associates subtests. Tests of EF included the D-KEFS Category Switching and Color Word Interference Tests, and the Trail Making Test. Using these measures, a principal component (PC) was derived for VM and for EF. Hierarchical multiple linear regression analysis was used to evaluate the unique contributions of BDI-II Score, VM PC, and EF PC to the QOLIE-31 Total Score, while controlling for important clinical and demographic variables. Post-hoc analyses were also performed to examine the contribution of each variable to specific QOLIE subscales. RESULTS: Of the clinical variables, only number of antiepileptic drugs contributed to QOLIE scores. As expected, severity of depressive symptoms was the most significant predictor of QOLIE Total Score, explaining 43.4% of the variance in total QoL. The VM PC did not contribute to the QOLIE Total Score. Rather, our EF PC emerged as an important predictor of QoL, explaining an additional 5% of the variance, after controlling for clinical variables, depression severity, and VM performance. SIGNIFICANCE: These findings suggest that a combination of clinical, affective, and cognitive factors influence QoL in patients with TLE. Designing interventions with careful attention to depression and EF may be needed to optimize QoL in patients with refractory TLE and potentially other epilepsy syndromes.

Mapping lexical-semantic networks and determining hemispheric language dominance: Do task design, sex, age, and language performance make a difference?

Blocked and event-related fMRI designs are both commonly used to localize language networks and determine hemispheric dominance in research and clinical settings. We compared activation profiles on a semantic monitoring task using one of the two designs in a total of 43 healthy individual to determine whether task design or subject-specific factors (i.e., age, sex, or language performance) influence activation patterns. We found high concordance between the two designs within core language regions, including the inferior frontal, posterior temporal, and basal temporal region. However, differences emerged within inferior parietal cortex. Subject-specific factors did not influence activation patterns, nor did they interact with task design. These results suggest that despite high concordance within perisylvian regions that are robust to subject-specific factors, methodological differences between blocked and event-related designs may contribute to parietal activations. These findings provide important information for researchers incorporating fMRI results into meta-analytic studies, as well as for clinicians using fMRI to guide pre-surgical planning.

Impaired spatial pattern separation performance in temporal lobe epilepsy is associated with visuospatial memory deficits and hippocampal volume loss.

Individuals with chronic temporal lobe epilepsy (TLE) experience episodic memory deficits that may be progressive in nature. These memory decrements have been shown to increase with the extent of hippocampal damage, a hallmark feature of TLE. Pattern separation, a neural computational mechanism thought to play a role in episodic memory formation, has been shown to be negatively affected by aging and in individuals with known hippocampal dysfunction. Despite the link between poor pattern separation performance and episodic memory deficits, behavioral pattern separation has not been examined in patients with TLE. We examined pattern separation performance in a group of 22 patients with medically-refractory TLE and 20 healthy adults, using a task hypothesized to measure spatial pattern separation with graded levels of spatial interference. We found that individuals with TLE showed less efficient spatial pattern separation performance relative to healthy adults. Poorer spatial pattern separation performance in TLE was associated with poorer visuospatial memory, but only under high interference conditions. In addition, left hippocampal atrophy was associated with poor performance in the high interference condition in TLE. These data suggest that episodic memory impairments in patients with chronic, refractory TLE may be partially due to less efficient pattern separation, which likely reflects their underlying hippocampal dysfunction.

Effects of Age and Gender on Recall and Recognition Discriminability.

OBJECTIVE: Recall and recognition memory abilities are known to decline with increasing age, yet much of the evidence stems from studies that used simple measures of total target recall or recognition. The California Verbal Learning Test-Second Edition (CVLT-II) includes a new measure of recall discriminability that is analogous to recognition discriminability. These discriminability measures yield more thorough assessments of recall and recognition by accounting for intrusion and false positive errors, respectively. Research also has shown that women outperform men on verbal episodic memory tests. However, gender differences in recall and recognition discriminability and the age-by-gender interaction on these constructs have not been thoroughly examined. METHOD: Cognitively healthy adults (N = 223) 18-91 years in age completed the CVLT-II. Multiple regression analyses were conducted to examine effects of age, gender, and the age-by-gender interaction on CVLT-II subtypes of recall and recognition discriminability. RESULTS: Discriminability scores decreased with increasing age, and women outperformed men. There was an age-by-gender interaction on total, immediate, and free recall discriminability - the negative association between age and scores was stronger in men than in women. Exploratory analyses revealed an inverted U-shaped relationship between age and recall discriminability scores in women. CONCLUSIONS: The present findings support and expand upon the extant literature on aging, gender, and verbal episodic memory, plus describe a novel age-by-gender interaction intrinsic to subtypes of recall discriminability. The findings suggest that methods traditionally used to assess recognition memory function can be used to elucidate age- and gender-related changes in recall ability across the adult lifespan.

Multimodal imaging of language reorganization in patients with left temporal lobe epilepsy.

This study explored the relationships among multimodal imaging, clinical features, and language impairment in patients with left temporal lobe epilepsy (LTLE). Fourteen patients with LTLE and 26 controls underwent structural MRI, functional MRI, diffusion tensor imaging, and neuropsychological language tasks. Laterality indices were calculated for each imaging modality and a principal component (PC) was derived from language measures. Correlations were performed among imaging measures, as well as to the language PC. In controls, better language performance was associated with stronger left-lateralized temporo-parietal and temporo-occipital activations. In LTLE, better language performance was associated with stronger right-lateralized inferior frontal, temporo-parietal, and temporo-occipital activations. These right-lateralized activations in LTLE were associated with right-lateralized arcuate fasciculus fractional anisotropy. These data suggest that interhemispheric language reorganization in LTLE is associated with alterations to perisylvian white matter. These concurrent structural and functional shifts from left to right may help to mitigate language impairment in LTLE.