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.
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.
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.
Summary: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. Key Words: Epileptic encephalopathyCognition-Epilepsy-Surround inhibition-FDG-PET.An epileptic encephalopathy is characterized by uncontrolled epileptic seizures associated with cognitive deterioration, and can occur both in children (Wirrell et al., 2005) and adults (Dodrill 2002;Helmstaedter et al., 2003;Thompson and Duncan 2005). The cause of the cognitive deterioration is unknown and may be due to antiepileptic drugs (AEDs), neuronal cell loss, the underlying etiology of the epilepsy or as a direct effect of seizures and epileptic activity. We describe a patient with prolonged status epilepticus (SE) and progressive cognitive deterioration, which slowly reversed after the control of epileptic seizures. We present evidence that this cognitive decline may be a seizure-related phenomenon, characterized by FDG-PET hypometabolism and EEG delta activity at a distance from the ictal onset zone, which we have called the surround inhibition zone (Nelissen et al., 2006;Van Paesschen et al., 2007). CASE DESCRIPTIONThe patient was a 25-year-old right-handed woman. Her gestation and birth were uneventful. She did not have a his-
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 %.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.