Browsing by Author "O'Neill, Darren P."

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    Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy
    (American Society of Clinical Oncology, 2016-03-01) Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.; Saykin, Andrew J.; IU School of Nursing
    PURPOSE: To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. METHODS: Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. RESULTS: Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). CONCLUSION: Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications.
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    Prophylactic Anticonvulsants in Intracerebral Hemorrhage
    (Springer, 2017-10) Mackey, Jason; Blatsioris, Ashley D.; Moser, Elizabeth A. S.; Carter, Ravan J. L.; Saha, Chandan; Stevenson, Alec; Hulin, Abigail L.; O'Neill, Darren P.; Cohen-Gadol, Aaron A.; Liepzig, Thomas J.; Williams, Linda S.; Neurology, School of Medicine
    Background and Purpose Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. Methods We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. Results We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95–0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76–4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40–3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51–6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10–5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4–6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. Discussion Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.
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    Resting-state fMRI Activity Profile in Prodromal Alzheimer’s Disease and Older Adults with Cognitive Complaints
    (Office of the Vice Chancellor for Research, 2013-04-05) Wang, Yang; West, John D.; Magee, Tamiko R.; McDonald, Brenna C.; Risacher, Shannon L.; Farlow, Martin R.; O'Neill, Darren P.; Saykin, Andrew J.
    Background: Resting-state functional MRI (RS-fMRI) has been proposed to detect neurodegenerative disease-related network alterations before brain atrophy has emerged. Disrupted resting-state connectivity in the posterior cingulate cortex (PCC) and hippocampus has been reported in AD (Grecius, 2004), yet results in prodromal AD including MCI vary. Other methods have suggested the feasibility of earlier detection in euthymic older adults with marked cognitive complaints (CC) but normal neuropsychological test performance (Saykin, 2006). The current study was designed to assess RS-fMRI patterns in CC compared with MCI, AD and healthy controls (HC). Methods: To date, 13 CC, 9 HC, 4 MCI and 3 AD participants were scanned at rest with eyes closed on a Siemens 3T. RS-fMRI was analyzed using FSL, AFNI and SPM8. For each individual, the sum of amplitude of low frequency fluctuation (ALFF; 0.01–0.1 Hz) was calculated at each voxel (Biswal, 2010). Using PCC seed ROIs adapted from Fox et al (2005) voxel-wise cross-correlation maps were generated for each subject. Group comparisons and covariate analyses were performed using SPM8 with age as a covariate. Results: Compared to HC, MCI/AD showed decreased ALFF in the PCC (p<0.01, corrected), but increased ALFF in bilateral hippocampi (p<0.01). The CC group consistently showed intermediate changes. ROI analyses indicated differences in ALFF of PCC (HC > CC > MCI/AD, p<0.05, effect size: 0.61), and ALFF of hippocampus (HC < CC < MCI/AD, p<0.01, effect size: 0.75). ALFF of PCC was positively correlated with neuropsychological performance (MMSE, DRS and CVLT; r=0.45 to 0.56, p<0.01), while hippocampal ALFF was negatively correlated with performance (r=-0.48 to -0.67, p<0.01). PCC seeded crosscorrelation maps showed decreased hippocampal connectivity in MCI/AD compared to HC or CC (p<0.01). Conclusions: RS-fMRI appears sensitive to early prodromal neurodegenerative changes in regions associated with AD, notably including pre-MCI individuals with CC. While there is decreased functional connectivity between PCC and hippocampus, regionally increased ALFF in hippocampus may indicate a compensatory mechanism in early prodromal AD.