Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Prediction of oxygen requirement in patients with COVID-19 using a pre-trained chest radiograph xAI model: efficient development of auditable risk prediction models via a fine-tuning approach.

Risk prediction requires comprehensive integration of clinical information and concurrent radiological findings. We present an upgraded chest radiograph (CXR) explainable artificial intelligence (xAI) model, which was trained on 241,723 well-annotated CXRs obtained prior to the onset of the COVID-19 pandemic. Mean area under the receiver operating characteristic curve (AUROC) for detection of 20 radiographic features was 0.955 (95% CI 0.938-0.955) on PA view and 0.909 (95% CI 0.890-0.925) on AP view. Coexistent and correlated radiographic findings are displayed in an interpretation table, and calibrated classifier confidence is displayed on an AI scoreboard. Retrieval of similar feature patches and comparable CXRs from a Model-Derived Atlas provides justification for model predictions. To demonstrate the feasibility of a fine-tuning approach for efficient and scalable development of xAI risk prediction models, we applied our CXR xAI model, in combination with clinical information, to predict oxygen requirement in COVID-19 patients. Prediction accuracy for high flow oxygen (HFO) and mechanical ventilation (MV) was 0.953 and 0.934 at 24 h and 0.932 and 0.836 at 72 h from the time of emergency department (ED) admission, respectively. Our CXR xAI model is auditable and captures key pathophysiological manifestations of cardiorespiratory diseases and cardiothoracic comorbidities. This model can be efficiently and broadly applied via a fine-tuning approach to provide fully automated risk and outcome predictions in various clinical scenarios in real-world practice.

Cognitive functioning and depressive symptoms in Fabry disease: A follow-up study.

Patients with Fabry disease (FD) have a high prevalence of depressive symptoms and can suffer from cognitive impairment, negatively affecting their life. The course of cognitive functioning and depressive symptoms in FD is unknown. The aim of this prospective cohort study was to describe changes in cognitive functioning and depressive symptoms and to identify related variables in patients with FD over 1 year. Assessments were conducted twice, using a neuropsychological test battery and the Centre of Epidemiological Studies Depression scale (CESD). Eighty-one patients were included of which 76 patients (94%) completed both assessments (age: 44 years, 34% men, 75% classical phenotype). A significant decrease in cognitive functioning was found in four patients (5%), with patients regressing from excellent to average/good. Changes were not related to sex, phenotype, stroke, IQ or CESD scores. CESD scores ≥16 were present in 29 patients (38%) at baseline. Using the reliable change index a decrease in CESD scores was found in six patients (8%). Decreased CESD scores were independently related to employing a positive and problem solving coping style and increased CESD scores to an avoiding and brooding coping style and worsening health perception. We found no major changes in cognitive functioning in patients with FD during 1 year follow-up making it an unsuitable outcome in FD treatment trials. Considering the high prevalence of persistent depressive symptoms, assessment of depressive symptoms should be part of routine follow-up. Altering coping styles and health perception may improve psychological well-being in FD.

Determinants of cerebral radiological progression in Fabry disease.

BACKGROUND AND AIM: It is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. The aim of this study was to determine the effect of ERT and clinical characteristics on progression of WMLs and infarctions on MRI in patients with FD. METHODS: MRIs were assessed for WMLs (Fazekas scale), infarctions and basilar artery diameter (BAD). The effect of clinical characteristics (renal and cardiac involvement, cardiovascular risk factors, cardiac complications, BAD) and ERT on WML and infarction progression was evaluated using mixed models. RESULTS: One hundred forty-nine patients were included (median age: 39 years, 38% men, 79% classical phenotype). Median follow-up time was 7 years (range: 0-13 years) with a median number of MRIs per patient of 5 (range: 1-14), resulting in a total of 852 scans. Variables independently associated with WML and infarction progression were age, male sex and a classical phenotype. Progression of WMLs and infarctions was not affected by adding ERT to the model, neither for the whole group, nor for early treated patients. Progression was highly variable among patients which could not be explained by other known variables such as hypertension, cholesterol, atrial fibrillation and changes in kidney function, left ventricular mass or BAD. CONCLUSION: Progression of WMLs and cerebral infarctions in FD is mainly related to age, sex and phenotype. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible.

Depressive symptoms in Fabry disease: the importance of coping, subjective health perception and pain.

BACKGROUND: Despite the high prevalence of depressive symptoms in Fabry disease (FD), it is unclear which patient characteristics are important in relation to these symptoms. Additionally, the impact of coping styles in relation to depressive symptoms in FD has been unexplored. Determining the impact of different factors relating to depressive symptoms in FD can guide both prevention and treatment of these symptoms. METHODS: Depressive symptoms (Center for Epidemiologic Studies Depression scale (CESD)) and coping styles (Utrecht Coping List) were assessed in a Dutch FD cohort. Other potentially important variables were identified from FD literature and assessed in this cohort. Relations were evaluated using multiple linear models. RESULTS: Potentially important variables in FD literature were: pain, unemployment, health perception, being single, comorbidities and stroke. Employed coping styles were "avoidance and brooding", "positivity and problem solving" and "seeking social support". Thirty-one of the 81 FD patients (38%) had depressive symptoms. CESD-scores were lower in patients with better health perception and more "positivity and problem solving" and higher in patients with more pain and "avoidance and brooding". The best model explained 70% (95%CI: 54-76%) of observed variance of the CESD. CONCLUSIONS: Depressive symptoms in FD are related to pain, negative health perception and use of specific coping styles. Psychological interventions could be employed to alter coping behavior and alleviate depressive symptoms.

Outcome and Feasibility after 7 Years of Therapeutic Hypothermia in Southern Brazil.

OBJECTIVE: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil. STUDY DESIGN: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age. RESULTS: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development. CONCLUSION: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately.

Predictors of objective cognitive impairment and subjective cognitive complaints in patients with Fabry disease.

This study investigates the relationship between objective cognitive impairment (OCI), subjective cognitive complaints and depressive symptoms in men and women with classical and non-classical Fabry disease (FD). Cognitive functioning was assessed using a neuropsychological test battery, subjective cognitive complaints using a structured interview and depressive symptoms using a depression scale (CESD). Eighty-one patients were included (mean age 44.5 ± 14.3, 35% men, 74% classical). Subjective cognitive complaints were reported by 64% of all patients. OCI was present in thirteen patients (16%), predominantly in men with classical FD. Thirty-one patients (38%) had a high score (≥16) on the CESD scale. Male sex (OR, 6.8; 95%CI, 1.6-39.8; p = 1.6 * 10-2) and stroke (OR, 6.4; 95% CI, 1.1-41.0; p = 3.7 * 10-2) were independently positively associated with OCI, and premorbid IQ (one IQ point increase: OR, 0.91; 95%CI, 0.82-0.98; p = 3.8 * 10-2) was independently negatively associated with OCI. The CESD-score (one point increase: OR, 1.07; 95% CI, 1.02-1.13; p = 3.3 * 10-3) and a history of depression (OR, 2.7; 95% CI, 1.1-7.3; p = 3.9 * 10-2) were independently positively associated with subjective cognitive complaints. OCI is present in 16% of FD patients, warranting referral for neuropsychological assessment. Nevertheless, subjective cognitive complaints are related to depressive symptoms, emphasizing the importance of recognition and treatment of the latter.

Simultaneous Multislice-Based 5-Minute Lumbar Spine MRI Protocol: Initial Experience in a Clinical Setting.

BACKGROUND AND PURPOSE: Previous studies have used parallel imaging (PI) techniques to decrease spine magnetic resonance imaging (MRI) protocol acquisition times. Recently developed MRI sequences allow even faster acquisitions. Our purpose was to develop a lumbar spine MRI protocol using PI with GRAPPA (generalized autocalibrating partially parallel acquisition) and a simultaneous multislice (SMS)-based sequence and to evaluate its diagnostic performance compared to a standard lumbar spine MRI protocol. METHODS: Ten patients were scanned in a 3-Tesla scanner (MAGNETOM Skyra, Siemens Healthcare). Each patient was imaged using a standard protocol and an optimized fast protocol acquiring the same contrasts and planes. The fast protocol included sagittal T1, T2, and fat suppressed T2 sequences accelerated with GRAPPA and an SMS-based axial T2-weighted sequence using a high-density spine coil (Siemens MR, 30 channel spine). Two blinded neuroradiologists independently assessed image quality and diagnostic accuracy for clinically relevant imaging findings. RESULTS: The fast protocol acquisition time was 5:28 minutes, compared with 16:30 minutes for the standard protocol. Both protocols had a similar performance for definition of anatomical structures, diagnostic quality, and identification of clinically relevant imaging findings. There were more artifacts in the SMS Turbo Spin Echo (P = .014) sequence without compromising diagnostic performance. Artifacts in the remaining non-SMS sequences were similar in both protocols (P > .180). The sensitivity, specificity, and accuracy of the 5-minute protocol were 92.3%, 100.0%, and 99.6%, respectively, for the clinically relevant findings (P = 1.0, interrater agreement .57). CONCLUSIONS: A 5-minute SMS-based MRI protocol for lumbar spine imaging is feasible and can be achieved without significant impact in the overall diagnostic quality.