Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients.

A subgroup of patients with breast cancer suffers from mild cognitive impairment after chemotherapy. To uncover the neural substrate of these mental complaints, we examined cerebral white matter (WM) integrity after chemotherapy using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Postchemotherapy breast cancer patients (n = 17) and matched healthy controls (n = 18) were recruited for DTI and neuropsychological testing, including the self-report cognitive failure questionnaire (CFQ). Differences in DTI WM integrity parameters [fractional anisotropy (FA) and mean diffusivity (MD)] between patients and healthy controls were assessed using a voxel-based two-sample-t-test. In comparison with healthy controls, the patient group demonstrated decreased FA in frontal and temporal WM tracts and increased MD in frontal WM. These differences were also confirmed when comparing this patient group with an additional control group of nonchemotherapy-treated breast cancer patients (n = 10). To address the heterogeneity observed in cognitive function after chemotherapy, we performed a voxel-based correlation analysis between FA values and individual neuropsychological test scores. Significant correlations of FA with neuropsychological tests covering the domain of attention and processing/psychomotor speed were found in temporal and parietal WM tracts. Furthermore, CFQ scores correlated negatively in frontal and parietal WM. These studies show that chemotherapy seems to affect WM integrity and that parameters derived from DTI have the required sensitivity to quantify neural changes related to chemotherapy-induced mild cognitive impairment.

Correlation of neuropsychological and metabolic changes after epilepsy surgery in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Epilepsy surgery often causes changes in cognition and cerebral glucose metabolism. Our aim was to explore relationships between pre- and postoperative cerebral metabolism as measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological test scores in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), who were rendered seizure-free after epilepsy surgery. RESULTS: Thirteen patients were included. All had neuropsychological testing and an interictal FDG-PET scan of the brain pre- and postoperative. Correlations between changes in neuropsychological test scores and metabolism were examined using statistical parametric mapping (SPM). There were no significant changes in the neuropsychological test scores pre- and postoperatively at the group level. Decreased metabolism was observed in the left mesial temporal regions and occipital lobe. Increased metabolism was observed in the bi-frontal and right parietal lobes, temporal lobes, occipital lobes, thalamus, cerebellum, and vermis. In these regions, we did not find a correlation between changes in metabolism and neuropsychological test scores. A significant negative correlation, however, was found between metabolic changes in the precuneus and Boston Naming Test (BNT) scores. CONCLUSIONS: There are significant metabolic decreases in the left mesial temporal regions and increases in the bi-frontal lobes; right parietal, temporal, and occipital lobes; right thalamus; cerebellum; and vermis in patients with left MTLE-HS who were rendered seizure-free after epilepsy surgery. We could not confirm that these changes translate into significant cognitive changes. A significant negative correlation was found between changes in confrontation naming and changes in metabolism in the precuneus. We speculate that the precuneus may play a compensatory role in patients with postoperative naming difficulties after left TLE surgery. Understanding of these neural mechanisms may aid in designing cognitive rehabilitation strategies.

Outcome after epilepsy surgery at the University Hospitals Leuven 1998-2012.

We performed a retrospective outcome study of 199 patients who underwent resective epilepsy surgery from 1998 to 2012 and had a minimum of one-year follow-up at the University Hospitals Leuven. Our aim was to assess seizure outcome, prognostic factors for seizure outcome and complication rate. Good seizure outcome after surgery was 38 % at 5 years and 34 % at 10 years follow-up. Good seizure outcome over the previous year at last follow-up, however, was 77 %, which could be explained by the 'running-down phenomenon', i.e. seizure freedom after initial recurrent epilepsy in 32 % of the patients, mainly after temporal lobe surgery. Good seizure outcome for at least 1 year at the last visit was 82 % for temporal and 62 % for extra-temporal lobe interventions. Other variables predictive of a good seizure outcome were not identified. Permanent complications of epilepsy surgery were observed in 31 %. The most important were word finding difficulties (22 %), depression (18 %) and memory deficits (12 %). In conclusion, epilepsy surgery is an excellent treatment option for selected patients, with a good seizure outcome in around 80 % of patients and complications in about 30 %.

Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients.

Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

Cognitive deficits during status epilepticus and time course of recovery: a case report.

We describe a young woman with progressive cognitive and neurological deficits during a parietal lobe status epilepticus (SE). Ictal FDG-PET showed left parietal lobe hypermetabolism and frontal lobe hypometabolism with concomitant EEG slowing. Cognitive and neurological deficits fully reversed more than 1 year after seizure remission, and were associated with normalization of FDG-PET and EEG. Our findings suggest that ictal hypometabolism and EEG delta activity at a distance from the epileptic focus were seizure-related phenomena, possibly representing inhibition in seizure propagation pathways, which could be responsible for the epileptic encephalopathy.

Paradoxical features of word finding difficulty in primary progressive aphasia.

Impaired word retrieval is a main symptom of primary progressive aphasia (PPA). The cognitive features of this impairment in PPA are poorly understood. We studied 12 patients with PPA (6 English-speaking and 6 Dutch-speaking), 7 patients with early-stage clinically probable Alzheimer's disease (PRAD), 5 patients with mild cognitive impairment (MCI), and 15 age-matched, cognitively intact, control subjects. Subjects had to name a picture (the probe), which was preceded by a written word (the prime) that could be the correct name of the picture, a noun belonging to the same semantic subcategory (related prime), a semantically unrelated noun (unrelated prime), or a pseudoword (neutral control). Naming latencies were longer in PPA and PRAD patients than in control subjects. Critically, the interaction between group and prime type was highly significant. PPA patients named the probe more slowly after a related compared with an unrelated prime. In contrast, PRAD patients, mild cognitive impairment patients, and healthy control subjects tended to name the probe faster when it was preceded by a related prime. The semantic interference effect in PPA generalized across languages and PPA subtypes. Selection among competing word forms sharing a same semantic field is abnormal in PPA. The semantic interference effect constitutes a positive distinguishing feature between PPA and PRAD.