Computerized cognitive training in post-treatment hematological cancer survivors: a feasibility study.

BACKGROUND: Computerized cognitive training (CCT) programs have shown some effectiveness in alleviating cognitive symptoms in long-term cancer survivors. For patients presenting with cognitive symptoms in the early post-treatment phase, the benefit of CCT is unclear. To assess the possibility of testing the effectiveness of CCT in the early post-treatment period, our aim was to investigate the feasibility of an 8-week home-based, online CCT intervention among patients who have recently completed treatment for hematological malignancy. METHODS: This study was a single-arm, non-blinded, feasibility study. All participants were provided with the CCT intervention for an 8-week period. Feasibility was evaluated based on participant adherence and patient perceptions of the intervention, assessed through responses to an acceptability questionnaire and semi-structured interviews at the end of the intervention period. RESULTS: The feasibility study included 19 patients who had completed treatment for hematological malignancy at a Canadian tertiary cancer center. Adherence to the CCT intervention was limited, with only one participant meeting the criteria for intervention adherence. At the end of the intervention period, participants characterized the program as easy to follow (92%) and felt well-prepared for how to complete the exercises (100%). In semi-structured interviews, participants highlighted post-treatment barriers to intervention adherence that included symptom burden and competing time demands. Participants also suggested improvements to the intervention that could help maintain adherence despite these barriers, such as fostering a sense of accountability, providing personalized feedback and coaching, and enabling opportunities for peer support. CONCLUSIONS: Participation in CCT can be challenging in the post-treatment period for hematological cancers. Further research on the effectiveness of CCT in this setting may require the implementation of strategies that support participants' engagement with the intervention in the context of symptoms and competing demands, such as establishing a minimum dose requirement and integrating approaches to help promote and sustain motivation.

Paraneoplastic opsoclonus-myoclonus syndrome as a rare presentation of breast cancer.

Opsoclonus-myoclonus paraneoplastic syndrome is a medical condition that includes opsoclonus along with diffuse or focal body myoclonus and truncal titubation with or without ataxia and other cerebellar signs. This rare neurological syndrome is poorly understood and can result in long-term cognitive, behavioral and motor sequelae. We report a case of a 49-year-old woman with anti-Ri antibody opsoclonus-myoclonus syndrome and an invasive ductal carcinoma with axillary nodes involvement. Following the diagnosis of opsoclonus-myoclonus syndrome, a multimodal immunotherapy treatment, with partial remission of the neurological symptoms. The patient underwent lumpectomy and axillary node dissection and the surgical pathology confirmed the diagnosis of breast cancer stage IIA. This was followed by chemotherapy, radiotherapy and hormone therapy with tamoxifen. At the 6 months follow-up there was a partial improvement, anti-Ri antibody was subsequently reported as negative and there was no evidence of disease recurrence.

Normal appearing white matter permeability: a marker of inflammation and information processing speed deficit among relapsing remitting multiple sclerosis patients.

PURPOSE: Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS). METHODS: Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression. RESULTS: rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068-2.956; p = 0.026), NAGM (OR 2.138; 1.100-4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120-4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups. CONCLUSION: rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.

The relationship between white matter fiber damage and gray matter perfusion in large-scale functionally defined networks in multiple sclerosis.

BACKGROUND: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. OBJECTIVE: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients. METHODS: Magnetic resonance imaging (MRI) and neurocognitive testing were performed on 19 healthy controls (HC), 39 RRMS, and 45 SPMS patients. WM damage extent and severity were quantified with T2-hyper/T1-hypointense (T2h/T1h) lesion volume and degree of perfusion reduction in lesional and normal-appearing white matter (NAWM), respectively. A two-step linear regression corrected for confounders was employed. RESULTS: Cognitive impairment was present in 20/39 (51%) RRMS and 25/45 (53%) SPMS patients. GM node perfusion was associated with WM fiber damage severity (WM hypoperfusion) within each network-including both NAWM ( R2 = 0.67-0.89, p < 0.0001) and T2h ( R2 = 0.39-0.62, p < 0.0001) WM regions-but was not significantly associated ( p > 0.01) with WM fiber damage extent (i.e. T2h/T1h lesion volumes). CONCLUSION: Overall, GM node perfusion was associated with severity rather than extent of WM network damage, supporting a primary etiology of GM hypoperfusion.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients.

BACKGROUND: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients.

PURPOSE: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. METHODS: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. RESULTS: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. CONCLUSION: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.