Proposing a quantitative MRI-based linear measurement framework for response assessment following stereotactic body radiation therapy in patients with spinal metastasis.

PURPOSE: To provide evidence towards a quantitative response assessment framework incorporating MRI-based linear measurements for spinal metastasis that predicts outcome following stereotactic body radiation therapy (SBRT). METHODS: Adult patients with de novo spinal metastases treated with SBRT between 2008 and 2018 were retrospectively assessed. The metastatic lesions involving the pedicles, articular processes, lamina, transverse process, spinous process and vertebral body at leach level were measured separately using linear measurements on pre- and all post-SBRT MRIs. The outcome was segment-specific progression (SSP) using SPINO guidelines which was dated to the first clinical documentation of progression, or the date of the associated MRI if imaging was the reason for progression. Random forest analysis for variable selection and recursive partitioning analysis for SSP probability prediction were used. RESULTS: Five Hundred Ninety-three spinal levels (323 patients) from 4081 MRIs were evaluated. The appearance of new T1 hypointensity and increase in Bilsky grade had an odds ratio (OR) of 33.5 and 15.5 for SSP, respectively. Compared to baseline, an increase of > 3 mm in any lesion dimension, combined with a 1.67-fold increase in area, had an OR of 4.6 for SSP. The sensitivity, specificity, positive predictive value, negative predictive value, balanced accuracy and area under the curve of the training model were 96.7%, 89.6%, 28.6%, 99.8%, 93.2% and 0.905 and of the test model were 91.3%, 89.3%, 27.1% 99.6%, 90.3% and 0.933, respectively. CONCLUSION: With further refinement and validation in prospective multicentre studies, MRI-based linear measurements can help predict response assessment in SBRT-treated spinal metastases.

Anticoagulation therapy in COVID-19 patients with chronic kidney disease.

Coagulopathy and derangements in the coagulation parameters are significant features of COVID-19 infection, which increases the risk of disseminated intravascular coagulation, thrombosis, and hemorrhage in these patients, resulting in increased morbidity and mortality. In times of COVID-19, special consideration should be given to patients with concurrent chronic kidney disease (CKD) and COVID-19 (CKD/COVID-19 patients) as renal dysfunction increases their risk of thrombosis and hemorrhage, and falsely affects some of the coagulation factors, which are currently utilized to assess thrombosis risk in patients with COVID-19. Hence, we believe extra attention should be given to determining the risk of thrombosis and bleeding and optimizing the timing and dosage of anticoagulant therapy in this unique population of patients. CKD/COVID-19 patients are considered a high-risk population for thrombotic events and hemorrhage. Furthermore, effects of renal function on paraclinical and clinical data should be considered during the evaluation and interpretation of thrombosis risk stratification. Individualized evaluation of clinical status and kidney function is necessary to determine the best approach and management for anticoagulant therapy, whereas there is a lack of studies about the population of CKD/COVID-19 patients who need anticoagulant therapy now.

White Matter Tract Alterations in Drug-Naïve Parkinson's Disease Patients With Excessive Daytime Sleepiness.

Excessive daytime sleepiness (EDS) is relatively frequent in patients with Parkinson's disease (PD), having a prominent burden on patients' quality of life and causing dangerous events such as motor-vehicle accidents. Previous studies have indicated the role of certain neural tracts in the pathophysiology of sleep disturbances, especially in PD patients. We hypothesized that white matter integrity and connectivity might be altered in patients with PD and EDS. Therefore, this study investigated brain white matter microstructure alterations in patients with Parkinson's disease with EDS (PD-EDS) compared to healthy controls and PD patients without EDS (PD-nEDS). Diffusion MRI connectometry was used to carry out group analysis between PD patients with and without EDS and healthy individuals. EDS in PD patients is associated with decreased connectivity in the left and right fornix, left and right inferior longitudinal fasciculus (ILF), left inferior and middle cerebellar peduncles in comparison to PD-nEDS group. These differences between PD-EDS and PD-nEDS patients reflects microstructural changes with respect to sleep-related circuits, which can pave the way for future investigations considering EDS pathogenesis in Parkinson's disease.

Posterior limb of the internal capsule predicts poor quality of life in patients with Parkinson's disease: connectometry approach.

Psychiatric symptoms and motor impairment are major contributions to the poor quality of life in patients with Parkinson's disease (PD). Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3 ± 2.9 years, H and Y stage = 1.5 ± 0.6, UPDRS-III = 13.7 ± 6.5, indicating unilateral and mild motor involvement). The connectometry analysis demonstrated bilateral posterior limbs of the internal capsule (PLIC) with increased connectivity related to the higher quality of life (FDR = 0.027) in a multiple regression model. The present study suggests for the first time a neural basis of the quality of life in PD in the light of major determinants of poor quality of life in these patients: anxiety, depression, apathy and motor impairment. Results in our sample of non-demented PD patients with relatively mild motor impairment and no apparent sign of depression/anxiety also identify a unique and inexplicable association of the PLIC to the quality of life in PD patients.

Serum Insulin-Like Growth Factor-1 in Parkinson's Disease; Study of Cerebrospinal Fluid Biomarkers and White Matter Microstructure.

Background: Growing evidence shows that impaired signaling of Insulin-like Growth Factor-1 (IGF-1) is associated with neurodegenerative disorders, such as Parkinson's disease (PD). However, there is still controversy regarding its proinflammatory or neuroprotective function. In an attempt to elucidate the contribution of IGF-1 in PD, we aimed to discover the relation between serum IGF-1 levels in drug-naïve early PD patients and cerebrospinal fluid (CSF) biomarkers as well as microstructural changes in brain white matter. Methods: The association between quartiles of serum IGF-1 levels and CSF biomarkers (α-synuclein, dopamine, amyloid-ß1-42, total tau, and phosphorylated tau) was investigated using adjusted regression models in 404 drug-naïve early PD patients with only mild motor manifestations and 188 age- and sex-matched healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). By using region of interest analysis and connectometry approach, we tracked the white matter microstructural integrity and diffusivity patterns in a subgroup of study participants with available diffusion MRI data to investigate the association between subcomponents of neural pathways with serum IGF-1 levels. Results: PD patients had higher levels of IGF-1 compared to HC, although not statistically significant (mean difference: 3.60, P = 0.44). However, after adjustment for possible confounders and correction for False Discovery Rate (FDR), IGF-1 was negatively correlated with CSF α-synuclein, total and phosphorylated tau levels only in PD subjects. The imaging analysis proved a significant negative correlation (FDR corrected P-value = 0.013) between continuous levels of serum IGF-1 in patients with PD and the connectivity, but not integrity, in following fibers while controlling for age, sex, body mass index, depressive symptoms, education years, cognitive status and disease duration: middle cerebellar peduncle, cingulum, genu and splenium of the corpus callosum. No significant association was found between brain white matter microstructral measures or CSF markers of healthy controls and levels of IGF-1. Conclusion: Altered connectivity in specific white matter structures, mainly involved in cognitive and motor deterioration, in association with higher serum IGF-1 levels might propose IGF-1 as a potential associate of worse outcome in response to higher burden of α-synucleinopathy and tauopathy in PD.

Microstructural Changes in Patients With Parkinson's Disease Comorbid With REM Sleep Behaviour Disorder and Depressive Symptoms.

The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.

Cerebrospinal Fluid C-Reactive Protein in Parkinson's Disease: Associations with Motor and Non-motor Symptoms.

Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms. Eighty-four healthy controls (HCs) and 109 PD subjects were entered into this study. A significant correlation was observed between CSF CRP levels and Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS part III) score and Montreal Cognitive Assessment (MoCA) score in PD patients. We found significant correlations between MoCA score and CSF CRP levels in female patients and between CSF CRP and MDS-UPDRS part III score and MoCA score in male patients. In linear regression, CSF CRP could predict 6.9 and 10% of changes in MDS-UPDRS part III score in all PD patients male PD patients, respectively. In summary, we confirmed that CSF concentrations of CRP are in correlation with motor and non-motor severity in PD subjects. Our findings suggest that neuroinflammation plays an important role in the initiation and probably progression of PD motor and non-motor symptoms, which may give us a better insight into the underlying pathologic mechanisms in PD.

Association Between Peripheral Inflammation and DATSCAN Data of the Striatal Nuclei in Different Motor Subtypes of Parkinson Disease.

The interplay between peripheral and central inflammation has a significant role in dopaminergic neural death in nigrostriatal pathway, although no direct assessment of inflammation has been performed in relation to dopaminergic neuronal loss in striatal nuclei. In this study, the correlation of neutrophil to lymphocyte ratio (NLR) as a marker of peripheral inflammation to striatal binding ratios (SBRs) of DAT SPECT images in bilateral caudate and putamen nuclei was calculated in 388 drug-naïve early PD patients [288 tremor dominant (TD), 73 postural instability and gait difficulty (PIGD), and 27 indeterminate] and 148 controls. NLR was significantly higher in PD patients than in age- and sex-matched healthy controls, and showed a negative correlation to SBR in bilateral putamen and ipsilateral caudate in all PD subjects. Among our three subgroups, only TD patients showed remarkable results. A positive association between NLR and motor severity was observed in TD subgroup. Besides, NLR could negatively predict the SBR in ipsilateral and contralateral putamen and caudate nuclei in tremulous phenotype. Nonetheless, we found no significant association between NLR and other clinical and imaging findings in PIGD and indeterminate subgroups, supporting the presence of distinct underlying pathologic mechanisms between tremor and non-tremor predominant PD at early stages of the disease.

White Matter Tract Alterations in Drug-Naïve Parkinson's Disease Patients With Impulse Control Disorders.

Impulse control disorders (ICDs) are relatively frequent in patients with Parkinson's disease (PD), although it is still unclear whether an underlying pathological process plays a significant role in the development of ICD in PD apart from dopaminergic replacement therapy. In this study, we have investigated alterations of white matter tract in drug-naïve PD patients with ICDs via diffusion MRI connectometry. Our results showed that disrupted connectivity in the complex network of dynamic connections between cerebellum, basal ganglia, cortex, and its spinal projections serves as the underlying neuropathology of ICD in PD not interfered with the contribution of dopaminergic replacement therapy. These findings provide the first evidence on involved white matter tracts in the neuropathogenesis of ICD in drug-naïve PD population, supporting the hypothesis that neural disturbances intrinsic to PD may confer an increased risk for ICDs. Future studies are needed to validate the attribution of the impaired corticocerebellar network to impulsivity in PD.