scholarly journals Case Report: Disruption of Resting-State Networks and Cognitive Deficits After Whole Brain Irradiation for Singular Brain Metastasis

2021 ◽  
Vol 15 ◽  
Author(s):  
Martin Kocher ◽  
Christiane Jockwitz ◽  
Christoph Lerche ◽  
Michael Sabel ◽  
Philipp Lohmann ◽  
...  
Keyword(s):  
Working Memory ◽  
Brain Metastasis ◽  
Cognitive Deficits ◽  
Resting State ◽  
Healthy Subjects ◽  
Connectivity Matrix ◽  
Resting State Networks ◽  
Whole Brain

Introduction: Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI.Methods: A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0 Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects.Results: At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white mater of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks.Conclusion: As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.

scholarly journals Working Memory Training and Cortical Arousal in Healthy Older Adults: A Resting-State EEG Pilot Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Chiara Spironelli ◽  
Erika Borella
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Pilot Study ◽  
Resting State ◽  
Training Group ◽  
Effect Sizes ◽  
Intrusion Errors ◽  
High Beta

The current pilot study aimed to test the gains of working memory (WM) training, both at the short- and long-term, at a behavioral level, and by examining the electrophysiological changes induced by training in resting-state EEG activity among older adults. The study group included 24 older adults (from 64 to 75 years old) who were randomly assigned to a training group (TG) or an active control group (ACG) in a double-blind, repeated-measures experimental design in which open eyes, resting-state EEG recording, followed by a WM task, i.e., the Categorization Working Memory Span (CWMS) task, were collected before and after training, as well as at a 6-month follow-up session. At the behavioral level, medium to large Cohen's d effect sizes was found for the TG in immediate and long-term gains in the WM criterion task, as compared with small gains for the ACG. Regarding intrusion errors committed in the CWMS, an index of inhibitory control representing a transfer effect, results showed that medium to large effect sizes for immediate and long-term gains emerged for the TG, as compared to small effect sizes for the ACG. Spontaneous high-beta/alpha ratio analyses in four regions of interest (ROIs) revealed no pre-training group differences. Significantly greater TG anterior rates, particularly in the left ROI, were found after training, with frontal oscillatory responses being correlated with better post-training CWMS performance in only the TG. The follow-up analysis showed similar results, with greater anterior left high-beta/alpha rates among TG participants. Follow-up frontal high-beta/alpha rates in the right ROI were correlated with lower CWMS follow-up intrusion errors in only the TG. The present findings are further evidence of the efficacy of WM training in enhancing the cognitive functioning of older adults and their frontal oscillatory activity. Overall, these results suggested that WM training also can be a promising approach toward fostering the so-called functional cortical plasticity in aging.

Salvage Surgical Resection After Linac-based Stereotactic Radiosurgery and Radiotherapy for Newly Diagnosed Brain Metastasis

2021 ◽  
Author(s):  
Ryosuke Matsuda ◽  
Takayuki Morimoto ◽  
Tetsuro Tamamoto ◽  
Nobuyoshi Inooka ◽  
Tomoko Ochi ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Cyst Formation ◽  
Histopathological Diagnosis ◽  
Newly Diagnosed ◽  
Long Term Follow Up

Abstract Purpose: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for brain metastasis.Methods: Between November 2009 and December 2018, we treated 427 consecutive patients with 919 lesions with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During the follow-up period, we treated 19 consecutive patients who underwent 21 SSRs for recurrence, radiation necrosis (RN), and cyst formation after SRS/fSRT for newly diagnosed brain metastasis. Two patients underwent multiple surgical resections. Brain metastasis originated from the lung (n=15, 78.9%), breast (n=3, 15.7%), and colon (n=1, 5.2%). Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 15 months (range: 2–76 months). The range of tumor volume at initial SRS/SRT was 0.121–21.459 cm3 (median: 2.188 cm3). Histopathological diagnosis after SSR was recurrence, RN and cyst formation in 13 and 6 cases, respectively. The median survival time from SSR and from initial SRS/SRT was 17 months and 74 months, respectively. The cases with recurrence had a significantly shorter survival time than those without recurrence (p=0.0453).Conclusion: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

scholarly journals The Hyperfocusing Hypothesis: A New Account of Cognitive Dysfunction in Schizophrenia

2019 ◽  
Vol 45 (5) ◽  
pp. 991-1000 ◽  
Author(s):  
Steven J Luck ◽  
Britta Hahn ◽  
Carly J Leonard ◽  
James M Gold
Keyword(s):  
Working Memory ◽  
Cognitive Processes ◽  
Cognitive Deficits ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Good Target ◽  
Processing Resources ◽  
Nonspecific Factors ◽  
New Treatments

Abstract Impairments in basic cognitive processes such as attention and working memory are commonly observed in people with schizophrenia and are predictive of long-term outcome. In this review, we describe a new theory—the hyperfocusing hypothesis—which provides a unified account of many aspects of impaired cognition in schizophrenia. This hypothesis proposes that schizophrenia involves an abnormally narrow but intense focusing of processing resources. This hyperfocusing impairs the ability of people with schizophrenia to distribute attention among multiple locations, decreases the number of representations that can simultaneously be maintained in working memory, and causes attention to be abnormally captured by irrelevant inputs that share features with active representations. Evidence supporting the hyperfocusing hypothesis comes from a variety of laboratory tasks and from both behavioral and electrophysiological measures of processing. In many of these tasks, people with schizophrenia exhibit supranormal effects of task manipulations, which cannot be explained by a generalized cognitive deficit or by nonspecific factors such as reduced motivation or poor task comprehension. In addition, the degree of hyperfocusing in these tasks is often correlated with the degree of impairment in measures of broad cognitive function, which are known to be related to long-term outcome. Thus, the mechanisms underlying hyperfocusing may be a good target for new treatments targeting cognitive deficits in schizophrenia.

scholarly journals MON-307 Prospective, Longitudinal Study of Glucose-Suppressed GH Levels in 87 Acromegaly Patients with IGF-1 Normalization After Surgical Therapy: Prognostic Value of Nadir GH Levels for Long-Term Remission or Recurrence

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pamela Freda ◽  
Jeffrey N Bruce ◽  
Carlos Reyes-Vidal ◽  
Yessica De Leon ◽  
Zhezhen Jin ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Prognostic Value ◽  
Relevant Information ◽  
Oral Glucose ◽  
Surgical Removal ◽  
Prospective Longitudinal Study ◽  
Normal Ranges ◽  
Prospective Longitudinal

Abstract Surgical removal of the GH-secreting tumor is the initial treatment of choice for acromegaly. Outcome of surgery is assessed by measuring IGF-1 and glucose-suppressed GH levels. IGF-1 normalization is an essential biochemical criterion for remission. The cut-off for nadir GH after oral glucose that signifies remission, however, is debated. It also remains unclear whether GH levels provide additional prognostic or clinically relevant information when IGF-1 results are definitive. To address this question, we examined how initial postoperative glucose-suppressed GH levels change over time on serial testing in patients who achieve initial remission as defined by IGF-1 normalization. We studied 87 acromegaly patients (48M, 39F) who achieved a normal IGF-1 level after surgery alone longitudinally from 1996 to 2019. All had GH measured before and 60, 90 and 120 minutes after 75 or 100 mg oral glucose (OGTT) at ≥ 3 months after surgery and GH and IGF-1 repeated ≥ 1 year later. GH was by measured by sensitive, 22KDa GH specific assays, either a IRMA (DSL, International Reference Standard (IRS) 88/624) or a chemiluminescence immunoassay (IDS-iSYS, IRS 98/574). OGTT Nadir GH levels were also measured in healthy subjects; n=46 (26 M, 20 F, ages 19-71 yr.) by DSL and n=46 (29 M, 17 F; ages 20-66 yr.) by IDS-iSYS. Nadir GH levels in acromegaly patients were compared to the 95%CI of healthy subjects’ mean and categorized relative to healthy subjects’ 97.5 percentile, which was 0.14 µg/L for both assays. IGF-1 levels were compared to age and gender adjusted normal ranges. Subjects were grouped based on initial nadir GH ≤ or > 0.14 µg/L and the patterns of change in nadir GH and IGF-1 at last follow up or until IGF-1 became elevated (i.e. recurrence). Follow up durations are given as median(range). In follow up, 73 patients remained in remission (normal IGF-1) and 14 had a recurrence (elevated IGF-1). Of the 73 in remission, 55 had initial nadir GH ≤ 0.14 µg/L that persisted to 10 yr.(1-22yr.) of follow up, 5 had initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 9(3-21)yr., 10 had GH > 0.14 µg/L that persisted at 5.5(2-22)yr., and 3 had GH > 0.14 µg/L that fell to ≤ 0.14 µg/L at 5(4-7)yr. of follow up. Of the 14 that recurred, 11 had an initial and persistent GH > 0.14 µg/L and developed an elevated IGF-1 level after 6(1-23) yr.. The 3 other patients that recurred had an initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 1-6 years later and subsequently developed an elevated IGF-1 level by 14-16 years of follow up. In summary, we found that the pattern of normal IGF-1 along with nadir GH > 0.14 µg/L on initial testing or developing with time, was associated with recurrence in 14/32 patients. We also found that initial nadir GH ≤ 0.14 µg/L was highly predictive of long-term persistent remission: 60/63 such patients remained in remission. In conclusion, glucose-suppressed GH levels are of prognostic value in acromegaly patients with normal IGF-1 after surgery.

scholarly journals Consistent resting-state networks across healthy subjects

2006 ◽  
Vol 103 (37) ◽  
pp. 13848-13853 ◽  
Author(s):  
J. S. Damoiseaux ◽  
S. A. R. B. Rombouts ◽  
F. Barkhof ◽  
P. Scheltens ◽  
C. J. Stam ◽  
...  
Keyword(s):  
Resting State ◽  
Healthy Subjects ◽  
Resting State Networks

Long-term cognitive deficits following posterior fossa tumor resection: A neuropsychological and functional neuroimaging follow-up study.

2009 ◽  
Vol 23 (6) ◽  
pp. 694-704 ◽  
Author(s):  
Hyo Jung De Smet ◽  
Hanne Baillieux ◽  
Peggy Wackenier ◽  
Mania De Praeter ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Posterior Fossa ◽  
Cognitive Deficits ◽  
Functional Neuroimaging ◽  
Tumor Resection ◽  
Posterior Fossa Tumor ◽  
Follow Up Study

scholarly journals Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome

2013 ◽  
Vol 31 (31) ◽  
pp. 3971-3979 ◽  
Author(s):  
Patrick G. Morris ◽  
Denise D. Correa ◽  
Joachim Yahalom ◽  
Jeffrey J. Raizer ◽  
David Schiff ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Karnofsky Performance Score ◽  
Whole Brain ◽  
Long Term Outcome ◽  
Reduced Dose ◽  
Brain Radiotherapy

Purpose A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Results Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33). Conclusion R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.

scholarly journals An Updated Review on Memantine Efficacy in Reducing Cognitive Dysfunction of Whole-brain Irradiation for Adult Patients with Brain metastasis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Anya jafari ◽  
Zahra Siavashpour ◽  
Mohammad Houshyari
Keyword(s):  
Brain Metastasis ◽  
Verbal Learning ◽  
Whole Brain Radiotherapy ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
Delayed Recognition

Context: Increased survival of patients with cancer raises the need to pay attention to long-term side effects. Patients with brain metastasis experienced cognition failure after whole-brain radiotherapy. This review aimed at concluding the efficacy of Memantine in preserving cognitive function by reducing the brain toxicity of whole-brain radiotherapy for metastatic brain cancers. Evidence Acquisition: Published studies evaluating memantine protective effects during brain metastasis radiotherapy were searched for in scientific databases (e.g., Embase, PubMed, Cochrane database, Google Scholar, Scopus) using keywords including whole-brain radiotherapy and Memantine. Results: A total of 4 prospective clinical trials were included in the review. Effects of Memantine on cognition tests were evaluated in these trials. A significantly better Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recognition at months 6 was achieved in RTOG 0614 and NRG CC001. Longer time to cognitive decline was found in the memantine arm of the RTOG trial and was statistically significant. Memantine effects were not statistically significant before 2 months. Conclusions: It seems reasonable to consider Memantine during radiation to prevent long-term cognitive failure in patients with brain metastasis due to the current results. Memantine improves cognition function during whole-brain radiotherapy (WBRT) without adding irreparable complications.

Sign in / Sign up

Export Citation Format

Share Document