Prediction of Cognitive Decline in Temporal Lobe Epilepsy and Mild Cognitive Impairment by EEG, MRI, and Neuropsychology.
ABSTRACT: Cognitive decline is a severe concern of patients with mild cognitive impairment. Also, in patients with temporal lobe epilepsy, memory problems are a frequently encountered problem with potential progression. On the background of a unifying hypothesis for cognitive decline, we merged knowledge from dementia and epilepsy research in order to identify biomarkers with a high predictive value for cognitive decline across and beyond these groups that can be fed into intelligent systems. We prospectively assessed patients with temporal lobe epilepsy (N?=?9), mild cognitive impairment (N?=?19), and subjective cognitive complaints (N?=?4) and healthy controls (N?=?18). All had structural cerebral MRI, EEG at rest and during declarative verbal memory performance, and a neuropsychological assessment which was repeated after 18 months. Cognitive decline was defined as significant change on neuropsychological subscales. We extracted volumetric and shape features from MRI and brain network measures from EEG and fed these features alongside a baseline testing in neuropsychology into a machine learning framework with feature subset selection and 5-fold cross validation. Out of 50 patients, 27 had a decline over time in executive functions, 23 in visual-verbal memory, 23 in divided attention, and 7 patients had an increase in depression scores. The best sensitivity/specificity for decline was 72%/82% for executive functions based on a feature combination from MRI volumetry and EEG partial coherence during recall of memories; 95%/74% for visual-verbal memory by combination of MRI-wavelet features and neuropsychology; 84%/76% for divided attention by combination of MRI-wavelet features and neuropsychology; and 81%/90% for increase of depression by combination of EEG partial directed coherence factor at rest and neuropsychology. Combining information from EEG, MRI, and neuropsychology in order to predict neuropsychological changes in a heterogeneous population could create a more general model of cognitive performance decline.
Project description:The objective of this cohort study was to compare neuropsychological outcomes following left temporal lobe resection (TLR) in patients with epilepsy who had or had not undergone prior invasive monitoring.Data were obtained from an institutional review board-approved, neuropsychology registry for patients who underwent epilepsy surgery at Cleveland Clinic between 1997 and 2013. A total of 176 patients (45 with and 131 without invasive EEG) met inclusion criteria. Primary outcome measures were verbal memory and language scores. Other cognitive outcomes were also examined. Outcomes were assessed using difference in scores from before to after surgery and by presence/absence of clinically meaningful decline using reliable change indices (RCIs). Effect of invasive EEG on cognitive outcomes was estimated using weighting and propensity score adjustment to account for differences in baseline characteristics. Linear and logistic regression models compared surgical groups on all cognitive outcomes.Patients with invasive monitoring showed greater declines in confrontation naming; however, when RCIs were used to assess clinically meaningful change, there was no significant treatment effect on naming performance. No difference in verbal memory was observed, regardless of how the outcome was measured. In secondary outcomes, patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using RCIs to define change. There were no outcome differences on other cognitive measures.Results suggest that invasive EEG monitoring conducted prior to left TLR is not associated with greater cognitive morbidity than left TLR alone. This information is important when counseling patients regarding cognitive risks associated with this elective surgery.
Project description:BACKGROUND:Patients with a lesion within the amygdala and uncus may develop temporal lobe epilepsy despite having functional mesial structures. Resection of functional hippocampus and surrounding structures may lead to unacceptable iatrogenic deficits. To our knowledge, there is limited descriptions of surgical techniques for selectively resecting the amygdala and uncus lesions while preserving the hippocampus in patients with language-dominant temporal lobe pathology. METHODS:Thirteen patients with language-dominant temporal lobe epilepsy related to amygdala-centric lesions were identified. Patients with sclerosis of the mesial structures or evidence of pathology outside of the amygdala-uncus region were excluded. Neuropsychological evaluation confirmed normal function of the mesial structures ipsilateral to the lesion. All patients were worked up with video-EEG, high-resolution brain MRI, neuro-psychology evaluation, and either Wada or functional MRI testing. RESULTS:All patients underwent selective resection of the lesion including amygdala and uncus with preservation of the hippocampus via a transcortical inferior temporal gyrus approach to the mesial temporal lobe. Pathology was compatible with glioneuronal tumors. Post-operative MRI demonstrated complete resection in all patients. Eight of the thirteen patients underwent post-operative neuropsychology evaluations and did not demonstrate any significant decline in tasks of delayed verbal recall or visual memory based on the Rey Auditory Verbal Learning Test (RAVLT). One patient showed a slight decrease in confrontation naming using the Boston Naming Test (BNT). Seizure freedom (Engel class I) was achieved in 12 of 13 patients. CONCLUSION:Selective transcortical amygdala and uncus resection with hippocampus preservation may be a reasonable way to achieve seizure control while sparing functional mesial structures.
Project description:This retrospective cohort study characterized cognitive and motor outcomes in a large sample of adults who underwent frontal lobe resections for treatment of pharmacoresistant epilepsy.Ninety patients who underwent unilateral frontal lobe resection for epilepsy (42 language-dominant hemisphere/48 nondominant hemisphere) between 1989 and 2014 completed comprehensive preoperative and postoperative neuropsychological evaluations that included measures of verbal and nonverbal intellectual functioning, attention/working memory, processing speed, language, executive functioning, verbal and visual memory, and motor functioning. Objective methods were used to assess meaningful change across a wide range of abilities and to identify factors associated with neuropsychological decline following frontal lobectomy. Detailed postoperative neuroimaging analysis was conducted to characterize region, extent, and volume of resection.Forty-eight percent of patients did not demonstrate meaningful postoperative declines in cognition and an additional 42% demonstrated decline in 1 or 2 cognitive domains. When cognitive decline was observed, it usually occurred on measures of intelligence, visuomotor processing speed, or executive functioning. Side and site of resection were unrelated to cognitive outcome, but played a role in decline of contralateral manual dexterity following supplementary motor area resection. Higher preoperative ability, older age at surgery, absence of a malformation of cortical development on MRI, and poor seizure outcome were related to cognitive decline on some measures, but had poor sensitivity in identifying at-risk patients.The vast majority of patients who undergo frontal lobectomy for treatment of pharmacoresistant epilepsy demonstrate good cognitive and motor outcomes.
Project description:To develop a clinically applicable memory functional MRI (fMRI) method of predicting postsurgical memory outcome in individual patients.In this prospective cohort study, 50 patients with temporal lobe epilepsy (23 left) and 26 controls underwent an fMRI memory encoding paradigm of words with a subsequent out-of-scanner recognition assessment. Neuropsychological assessment was performed preoperatively and 4 months after anterior temporal lobe resection, and at equal time intervals in controls. An event-related analysis was used to explore brain activations for words remembered and change in verbal memory scores 4 months after surgery was correlated with preoperative activations. Individual lateralization indices were calculated within a medial temporal and frontal region and compared with other clinical parameters (hippocampal volume, preoperative verbal memory, age at onset of epilepsy, and language lateralization) as a predictor of verbal memory outcome.In left temporal lobe epilepsy patients, left frontal and anterior medial temporal activations correlated significantly with greater verbal memory decline, while bilateral posterior hippocampal activation correlated with less verbal memory decline postoperatively. In a multivariate regression model, left lateralized memory lateralization index (?0.5) within a medial temporal and frontal mask was the best predictor of verbal memory outcome after surgery in the dominant hemisphere in individual patients. Neither clinical nor functional MRI parameters predicted verbal memory decline after nondominant temporal lobe resection.We propose a clinically applicable memory fMRI paradigm to predict postoperative verbal memory decline after surgery in the language-dominant hemisphere in individual patients.
Project description:OBJECTIVE:A 71-year-old (MN) with an 11-year history of left onset tremor diagnosed as Parkinson's disease (PD) completed longitudinal brain magnetic resonance imaging (MRI) and neuropsychological testing. MRI scans showed an asymmetric caudate nucleus (right < left volume). We describe this asymmetry at baseline and the progression over time relative to other subcortical gray, frontal white matter, and cortical gray matter regions of interest. Isolated structural changes are compared to MN's cognitive profiles. METHOD:MN completed yearly MRIs and neuropsychological assessments. For comparison, left onset PD (n = 15) and non-PD (n = 43) peers completed the same baseline protocol. All MRI scans were processed with FreeSurfer and the FMRIB Software Library to analyze gray matter structures and frontal fractional anisotropy (FA) metrics. Processing speed, working memory, language, verbal memory, abstract reasoning, visuospatial, and motor functions were examined using reliable change methods. RESULTS:At baseline, MN had striatal volume and frontal lobe thickness asymmetry relative to peers with mild prefrontal white matter FA asymmetry. Over time only MN's right caudate nucleus showed accelerated atrophy. Cognitively, MN had slowed psychomotor speed and visuospatial-linked deficits with mild visuospatial working memory declines longitudinally. CONCLUSIONS:This is a unique report using normative neuroimaging and neuropsychology to describe an individual diagnosed with PD who had striking striatal asymmetry followed secondarily by cortical thickness asymmetry and possible frontal white matter asymmetry. His decline and variability in visual working memory could be linked to ongoing atrophy of his right caudate nucleus.
Project description:BACKGROUND:Deep brain stimulation (DBS) is effective for treatment of motor complications of dopaminergic therapy in Parkinson's disease (PD) but occasionally has been associated with multidomain cognitive decline. Patient- and caregiver-reported cognitive decline are clinically meaningful and increasingly recognized as important to consider when evaluating therapeutic interventions for PD. OBJECTIVE:The objective was to assess presurgical neuropsychological and clinical factors associated with PD patient- and caregiver-reported cognitive decline in two or more domains after DBS. METHOD:A single telephone survey was used to assess patient- and caregiver-reported cognitive decline in five domains at both one and four months after DBS surgery. Decline in two or more domains was considered multidomain cognitive decline (MDCD). Baseline demographic, clinical, and neuropsychological factors were compared in those with or without MDCD. Preoperative neuropsychological measures were evaluated as risk factors and regressed on the presence of MDCD, with demographic covariates, using multiple logistic regression. RESULTS:Preoperative performance in verbal recognition memory, language knowledge, and verbal processing decline were associated with postoperative, patient-reported MDCD in the first four weeks. MDCD at four months after DBS was associated with worse preoperative verbal reasoning, verbal recall, and semantic verbal fluency. Caregiver-reported MDCD one month after DBS was associated with poorer baseline verbal memory recognition accuracy/discriminability, visuospatial problem solving, and constructional praxis. CONCLUSION:Poor presurgical performance in verbal memory recognition, language processing, and visuospatial performance is associated with patient- or caregiver-reported decline following DBS surgery. Posterior cortical dysfunction seems to portend significant self-reported cognitive decline following deep brain stimulation.
Project description:Dysembryoplastic neuroepithelial tumors (DNTs) provide a unique model for studying the effects of seizures on cognitive development. Epilepsy and antiepileptic medications are prominent features in the lives and schooling of people who develop seizures in childhood. People with an adult onset share the same underlying brain pathology, but their childhood development is unaffected by seizures. Therefore, DNTs provide a model to examine the specific influence of seizures and their treatment on cognitive development, over and above the effects of the underlying pathology in epilepsy.We examined the neuropsychological characteristics of 56 adults with DNT and medically intractable epilepsy (mean age 32.7 years). Twenty-two adults (39%) had an age of onset of epilepsy before the age of 12 years (childhood-onset group). Scores on tests of intelligence (Verbal IQ and Performance IQ), reading, working memory, verbal learning, verbal recall, visual learning, and expressive and receptive language ability were analyzed.There were no significant localization effects (right vs. left vs. extratemporal) on any of the neuropsychological test scores. In the group as a whole, the neuropsychological test scores were significantly lower than healthy, age-matched controls on measures of Verbal IQ (p < 0.01), naming p < 0.01, verbal learning (p < 0.01), and working memory (p < 0.05). The childhood-onset group had significantly lower scores on the measures of Verbal IQ (p < 0.01), Performance IQ (p < 0.05), reading (p < 0.05), naming (p = 0.05), and verbal retention (p < 0.05) than those with an onset of seizures at the age of 12 or older.The traditional pattern of lateralized memory deficits seen in people with hippocampal sclerosis may not be present in people with temporal lobe epilepsy associated with a DNT. The presence of seizures and their treatment in early childhood may adversely influence the development of these core cognitive abilities, resulting in patterns of cognitive deficits that remain apparent in adulthood.
Project description:Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.
Project description:<h4>Objective</h4>The aim of this study was to determine if there were focal cortical abnormalities in juvenile myoclonic epilepsy (JME) using neuropsychological investigations and MRI.<h4>Methods</h4>Twenty-eight patients with JME and a large sample of healthy controls were assessed using a series of neuropsychological tests as well as structural and diffusion tensor MRI (DTI). DTI measures assessed fractional anisotropy (FA) within a white matter skeleton.<h4>Results</h4>Neuropsychological testing indicated subtle dysfunctions in verbal fluency, comprehension, and expression, as well as nonverbal memory and mental flexibility. Utilizing whole-brain voxel-based morphometry for gray matter MRI data and tract-based spatial statistics for white matter diffusion MRI data, we found reductions in gray matter volume (GMV) in the supplementary motor area and posterior cingulate cortex and reductions in FA in underlying white matter of the corpus callosum. Supplementary motor area FA predicted scores in word naming tasks and expression scores. Posterior cingulate cortex GMV and FA predicted cognitive inhibition scores on the mental flexibility task.<h4>Conclusions</h4>The neuropsychological, structural, and tractography results implicate mesial frontal cortex, especially the supplementary motor area, and posterior cingulate cortex in JME.
Project description:OBJECTIVE:Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. METHODS:In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. RESULTS:Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. CONCLUSION:Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.