Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease.

OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans. METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation. INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

Brain Abscess Apparent Diffusion Coefficient is Associated With Microbial Culture Yields.

BACKGROUND: Obtaining pus for microbial cultures is one of the surgical aims in patients with brain abscess. Predictors of microbial yields are necessary as they help in treatment planning. PURPOSE: To investigate the relationship between microbial culture yields of brain abscesses and their apparent diffusion coefficient (ADC) values and clinical characteristics. STUDY TYPE: Retrospective. SUBJECTS: Eighty-four patients diagnosed with brain abscess by surgery and histopathology (59 with positive abscess cultures). FIELD STRENGTH/SEQUENCE: Diffusion-weighted, T2-weigthed, and contrast-enhanced T1-weighted imaging at 1.5 T and 3 T. ASSESSMENT: Contrast-enhanced T1-weighted images were co-registered to ADC maps. Three neuroradiologists determined abscess imaging characteristics (distribution, location, and ventricular rupture), and two measured abscess volumes and ADC values. Clinical characteristics collected included sex, age, fever, underlying diseases, infection sources, white blood cell count, percentage of segmented neutrophils, C-reactive protein level, regimen and duration of empirical antibiotics, and types of surgery. STATISTICAL TESTS: Interobserver differences were assessed with Fleiss kappa and intraclass correlation coefficients. The differences in clinical and imaging factors between the positive and negative culture groups were compared with Chi-square analysis or Student's t test. All factors were subjected to multivariable logistic regression analysis to assess their associations with microbial culture yields, and factors with statistical significance were evaluated with receiver operating characteristic curve analysis to assess their diagnostic performance in discriminating the two groups. RESULTS: Mean ADC (×10-6  mm2 /s) of culture-negative abscesses (841 ± 173) was significantly higher (P < 0.05) than that of culture-positive abscesses (536 ± 90). On multivariable analysis, mean ADC was the only significant factor (P < 0.05) related to culture yields. With 660 as the cutoff value, the sensitivity, specificity, and accuracy of ADC for discriminating culture yields were 93.2%, 88.0%, and 91.7%, respectively. DATA CONCLUSION: ADC could be used to discriminate between culture-positive and culture-negative abscesses. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Peritumoral brain edema volume in meningioma correlates with tumor fractional anisotropy but not apparent diffusion coefficient or cerebral blood volume.

PURPOSE: Pathogenesis of peritumoral brain edema (PTBE) in meningiomas remains unclear. Associations between PTBE volume and diffusion or perfusion properties of meningioma have not been studied. We aimed to investigate if diffusion and perfusion properties of meningioma correlate with its PTBE volume. METHODS: Seventy consecutive patients (mean age, 58.9 ± 13.7 years; 37 women) with meningiomas who had preoperative DTI and DSC-PWI were retrospectively analyzed. PTBE volume, tumor volume, and mean T2 signal, ADC, FA, and CBV of the tumor were measured. Between meningiomas with and without PTBE, patient age and sex, as well as T2 signal intensity, volume, ADC, FA, and CBV of tumors, were compared. In meningiomas with PTBE, correlations of PTBE volume with patient age and sex, as well as T2 signal intensity, volume, ADC, FA, and CBV of tumors, were analyzed. Multivariable linear regression analysis was performed to identify factors associated with PTBE volume. RESULTS: On univariable analysis, meningiomas without PTBE were more frequently found in women (P = 0.033) and demonstrated lower ADC (P = 0.020), higher FA (P < 0.001), and lower CBV (P < 0.001). PTBE volume of meningiomas correlated with tumor ADC (r = 0.444; P = 0.001), tumor FA (r = - 0.655; P < 0.001), and tumor CBV (r = 0.402; P = 0.003). On multivariable analysis, tumor FA was the only factor associated with PTBE volume (P < 0.001). CONCLUSION: PTBE volume in meningioma correlates with tumor FA. DTI may help to understand the mechanism of PTBE in meningiomas.

Can we predict intraoperative blood loss in meningioma patients? Application of dynamic susceptibility contrast-enhanced magnetic resonance imaging.

PURPOSE: To evaluate the potential of quantitative dynamic susceptibility contrast (DSC) perfusion MR imaging parameters as imaging biomarkers for predicting intraoperative blood loss in meningioma. METHODS: Fifty-one non-embolized meningioma patients who had undergone preoperative DSC perfusion MR imaging were retrospectively included. The corrected relative cerebral blood volume (rCBV) and leakage coefficient (K2) of the entire enhanced tumor were obtained using leakage correction. Tumor volume, location, grade, and other clinical variables, were also analyzed. To investigate the vascularity and vascular permeability of meningiomas, and their correlation with predicting estimated blood loss (EBL) using preoperative DSC perfusion MR imaging, the authors proposed an index reflecting the inherent tendency of meningiomas to bleed after controlling volume (i.e., EBL/cm3). Simple regression was performed to identify predictors of EBL/cm3; subsequently, the relevant variables included in the stepwise multiple linear regression. RESULTS: On univariate analysis, EBL/cm3 was correlated with rCBV (r=0.677; P<0.001), K2 (r=0.294; P=0.036), and tumor volume (r=-0.312, P=0.026). EBL/cm3 was not correlated with age (P=0.873), sex (P=0.404), tumor location (P=0.327), or histological grade (P=0.230). On multiple linear regression, rCBV (ß=0.663 [0.463-0.864], B=1.293 [0.903-1.684; P<0.001) and K2 (ß=0.260 [0.060-0.460], B=2.277 [0.523-4.031], P=0.012), were the only independent predictors of EBL/cm3. CONCLUSION: The rCBV and K2 derived from DSC perfusion MR imaging in meningiomas may serve as feasible tools for clinicians to predict intraoperative blood loss and facilitate surgical planning.

Prognostic impact of combining whole-body PET/CT and brain PET/MR in patients with lung adenocarcinoma and brain metastases.

PURPOSE: The role of brain FDG-PET in patients with lung cancer and brain metastases remains unclear. Here, we sought to determine the prognostic significance of whole-body PET/CT plus brain PET/MR in predicting the time to neurological progression (nTTP) and overall survival (OS) in this patient group. METHODS: Of 802 patients with non-small cell lung cancer who underwent primary staging by a single-day protocol of whole-body PET/CT plus brain PET/MR, 72 cases with adenocarcinoma and brain metastases were enrolled for a prognostic analysis of OS. On the basis of the available follow-up brain status, only 52 patients were eligible for prognostic analysis of nTTP. Metastatic brain tumors were identified on post-contrast MR imaging, and the tumor-to-brain ratio (TBR) was measured on PET images. RESULTS: Multivariate analysis revealed that FDG-PET findings and eligibility for initial treatment with targeted therapy were significant independent predictors of nTTP and OS. A new index, termed the molecular imaging prognostic (MIP) score, was proposed to define three disease classes. MIP scores were significant predictors of both nTTP and OS (P < 0.001). Pre-existing prognostic indices such as Lung-molGPA scores were significant predictors of OS but did not predict nTTP. CONCLUSIONS: When staging is performed with whole-body PET/CT plus brain PET/MR, our new prognostic index may be helpful to stratify the outcomes of patients with lung adenocarcinoma and brain metastases. The superior prognostic power of this index for nTTP might be used to select appropriate patients for intracranial control and thereby achieve better quality of life.

Baseline multicentric tumors, distant recurrences and leptomeningeal dissemination predict poor survival in patients with recurrent glioblastomas receiving bevacizumab.

PURPOSE: There are no widely accepted MRI markers that predict treatment outcomes of bevacizumab among patients with recurrent glioblastoma (GB). We aimed to determine if conventional MRI features of recurrent GB predict survival of patients receiving bevacizumab. METHODS: Patients with recurrent GB were retrospectively included if they received bevacizumab monotherapy between 2008 and 2017 after failure of standard treatment. Their MRI studies obtained at baseline and tumor recurrence, prior to bevacizumab treatment, were evaluated for multiple MRI features including measurable tumor, baseline multicentric tumors, distant recurrence, non-contrast-enhancing tumor, deep white matter invasion, multiple parenchymal tumors, bilateral cerebral involvement, ependymal extension and leptomeningeal dissemination. Predictive values of MRI features and patient characteristics on patient survival were statistically analyzed. RESULTS: A total of 103 patients were included. Baseline multicentric tumors (OR = 4.07; P = 0.042) and distant recurrence (OR = 28.5; P < 0.001) were two significant predictors of 3-month progression-free survival (PFS) rate. Distant recurrence (HR = 3.94; P < 0.001) was the only independent predictor of PFS. Baseline multicentric tumors (HR = 1.97; P = 0.028), distant recurrence (HR = 4.73; P < 0.001) and leptomeningeal dissemination (HR = 2.28; P = 0.044) were three independent predictors of overall survival. CONCLUSIONS: Baseline multicentric tumors, distant recurrence and leptomeningeal dissemination predicted poor survival among patients receiving bevacizumab for recurrent GB. Conventional MRI may help selecting patients with recurrent GB for bevacizumab treatment.

Diffusion-Weighted Imaging of Periventricular Leukomalacia in Very Young Children: Assessment of Peritrigonal Stripe of Restricted Diffusion.

Purpose In periventricular leukomalacia (PVL), apparent diffusion coefficient (ADC) reduction, normally shown as dark stripe in the peritrigonal (PT) white matter, may be incomplete. We assessed the PT dark stripe to differentiate between PVL patients and control subjects. Patients and Methods We reviewed the magnetic resonance studies of 27 neonates and young children with PVL and 67 control subjects to assess the PT dark stripe on ADC maps. In PVL patients, the assessment was referred to the location of PVL lesion on fluid-attenuated inversion recovery (FLAIR) imaging. In the controls, the PT region or the location corresponding to FLAIR hyperintensity was evaluated for the dark stripe. We compared the prevalence of the dark stripe on ADC map and the PT FLAIR hyperintensity between the PVL and the control subjects. Results On ADC map, complete PT dark stripe was present in 67 (100%) of 67 controls but only in 4 (14.8%) of 27 PVL patients (p-value < 0.01), with sensitivity of 0.85, specificity of 1.0, and accuracy of 0.96. PT FLAIR hyperintensity was present in 44 (65.7%) of 67 controls and in 18 (66.7%) of 27 PVL patients (p = 0.920). Conclusion PVL patients can be differentiated from the control subjects with PT dark stripe on ADC map.

Arterial spin-labeling perfusion imaging of children with subdural hemorrhage: Perfusion abnormalities in abusive head trauma.

BACKGROUND AND PURPOSE: Perfusion abnormalities have not been well described in children with subdural hemorrhage (SDH). We investigated whether patients with abusive head trauma (AHT+) had more perfusion abnormalities than those without (AHT-). MATERIALS AND METHODS: We reviewed the perfusion MR studies of 12 infants with SDH and 21 controls. The perfusion images were obtained using a pseudo-continuous arterial spin-labeling sequence with volumetric fast spin-echo readout. An MR perfusion scoring system (0-6 points) was devised to facilitate appraisal of the extent of abnormalities. An asymmetry index (AI) was calculated for each region of perfusion abnormality. Comparison of perfusion scores across the AHT+, AHT-, and control groups was performed. The AIs of the hypoperfused lesions and hyperperfused lesions in patients were separately compared with those of the controls. The neurological outcomes of the patients were associated with imaging abnormalities. RESULTS: Perfusion abnormalities were found in five (83%) of six AHT+ patients and in one (17%) of six AHT- patients. The AHT+ group recorded a significantly higher perfusion score than did both the AHT- group and the controls. Four patients with hypoperfused lesions exhibited significantly lower AI (P=.002) than did the controls, and three patients with hyperperfused lesions had significantly higher AI (P=.006) than did the controls. Of the four patients with hypoperfused lesions, two expired and one experienced hemiparesis. CONCLUSIONS: Patients with AHT have higher perfusion abnormality scores than patients with other causes of SDH and controls. Moreover, hypoperfusion may suggest a poor clinical outcome.

Arterial spin-labeling perfusion imaging of childhood meningitis: a case series.

INTRODUCTION: Conventional magnetic resonance imaging (MRI), which is mainly used to detect complications, is ineffective in determining the neurological status of patients with meningitis. Hemodynamic change in the brain may be more indicative of the neurological status but few imaging studies have verified this. Arterial spin-labeling (ASL) perfusion, a noninvasive MR method requiring no contrast agent injection, can be used to measure cerebral blood flow (CBF). CASE REPORTS: We describe three pediatric patients with meningitis, who all showed regions of increased CBF on perfusion imaging. One patient, presenting with headache and conscious disturbance, had CBF changes in the frontal, temporal, and occipital regions. The other two patients, presenting with hallucinations, memory deficits, and seizures, had CBF changes in the frontal and temporal regions. CONCLUSION: ASL perfusion imaging may be helpful in assessing patients with meningitis, demonstrating CBF changes more strongly correlating with the neurological status, and detecting active brain abnormalities.

Childhood encephalitis: relationship between diffusion abnormalities and clinical outcome.

INTRODUCTION: The impact of restricted diffusion on clinical outcome has not been well studied in childhood encephalitis. We hypothesized that the patients with lesions with restricted diffusion (LRD) would have worse clinical outcome. METHODS: We reviewed the MR studies of 83 children with encephalitis for LRD. An MRI scoring system (0-12) based on fluid-attenuated inversion recovery (FLAIR) imaging was created to evaluate the extent of imaging abnormality. Clinical outcome was graded by using Glasgow outcome scale (GOS) (1-5) in 1st and 12th month: 1 for death and five for full recovery. With respect to diffusion, the correlation between imaging score and GOS was assessed. Logistic regression analysis was used to explore the impact of diffusion and imaging score on clinical outcome. The patients were divided into three subgroups regarding imaging score: I, 0-4; II, 5-8; and III, 9-12. RESULTS: LRD was found in 28 patients. Negative significant correlation was found between imaging score and GOS in the group with LRD in both 1st month (R = -0.67, P < 0.001) and 12th month (R = -0.56, P = 0.001). Multivariate logistic regression showed that LRD (P < 0.001) and age (P = 0.026) were significant independent risk factors for unfavorable outcome in 1st month, and both LRD (P = 0.001) and imaging score (P = 0.043) were significant risk factors for unfavorable outcome in 12th month. CONCLUSIONS: Patients with LRD have a worse clinical outcome than those without LRD. In patients with LRD, those with a greater extent of abnormality have a poorer outcome.

Unusual clinical presentation of cervical extradural meningioma detected with neuromuscular ultrasound: A case report.

Extradural meningiomas are rare in the cervical region. A total of 70-77% of reported cases have occurred in the thoracic region. Tumors that occur in the cervical region may invade the adjacent nerve root and brachial plexus. Typically, diagnoses of extradural meningioma are made after patients present with signs of myelopathy, such as progressive paresis and numbness. In the current study, a 64-year-old male patient presented with neck pain, numbness and mild weakness in the left hand over a 6-month period. The general neurological examination was unremarkable, except for mild grasping weakness on the left side. Needle electromyography revealed complex repetitive discharges in the left 5 and 6th cervical paraspinal muscles. Neuromuscular ultrasound revealed a lesion over the left 7th cervical root, which enabled the early detection of an extradural meningioma before notable focal neurological defects developed. The patient underwent a subtotal tumor excision, followed by radiotherapy for residual tumor. Histopathological examination confirmed atypical meningioma.

Sclerotherapy with intralesional bleomycin injection under guidance of multi-slice CT for retrobulbar orbital low-flow vascular lesions-single-center experience.

OBJECTIVE: This study investigated the safety and efficacy of sclerotherapy with intralesional bleomycin injection (IBI) for retrobulbar orbital low-flow vascular lesions under multi-slice computed tomography (CT) guidance. METHODS: Between January 2010 and September 2021, consecutive patients with retrobulbar orbital low-flow vascular lesions who underwent CT-guided IBI at a tertiary centre in Taiwan were enrolled. Their medical records and imaging data were retrospectively collected. RESULTS: This study enrolled 13 patients (7 male and 6 female patients; age range: 1-57 years; mean age: 25.9 years) with lymphatic malformation (LM, n = 4), venolymphatic malformation (n = 1), and venous malformation (VM, n = 8). The overall radiological response rate was 76.9% (10 of 13); the radiological response rate was 75.0% in the VM group (6 of 8) and 75.0% in the LM group (3 of 4). Moreover, 3 patients (23.1%) had minor complications and 1 (7.7%) had a major complication. The mean clinical and radiological follow-up was 8.3 months and no recurrence or progression was reported. CONCLUSION: CT-guided IBI is an effective and relatively safe minimally invasive treatment for retrobulbar orbital low-flow vascular lesions, with an overall radiological response rate of 76.9% in a mean of 1.5 sessions and a low complication rate. ADVANCES IN KNOWLEDGE: CT-guided sclerotherapy with IBI is a relatively safe, effective, and feasible alternative treatment option for retrobulbar orbital low-flow vascular lesions.

Solitary intracranial osteoma with attachment to the falx: a case report.

BACKGROUND: Intracranial osteomas are uncommon lesions that usually arise from the inner table of the cranium. There are few reports in the literature of intracranial osteomas with meninges attachment and without direct relation with the skull bone; these osteomas were mostly attached with dura. We report a rare osteoma with falx attachment. CASE: A 64-year-old woman presented with a 3-month history of intermittent tinnitus and dizziness. The scout film of petrous bone computed tomography scan revealed a high-density lesion in the frontal area. Magnetic resonance imaging showed a 2.5-cm mass attached to the surface of the falx in the right frontal parasagittal area. The patient underwent right frontal craniotomy, and a bony hard mass was found located in the right frontal parasagittal region extra-axially, with its medial surface attached to the falx. It could not be broken down by the cavitron ultrasonic surgical aspirator or even the cutting loop and was detached from the falx and removed in one piece. Histopathological examination showed a nodule with bony trabeculae and bone marrow tissue, compatible with osteoma. The postoperative course was uneventful, and the patient was discharged from the hospital with no neurological deficits one week after operation. CONCLUSIONS: This is the first case report in the English literature of an intracranial osteoma arising from the falx. Because of their slow growth and their locations in silent brain areas, intracranial osteomas are usually diagnosed incidentally. Surgical resection is the primary treatment choice.

Angular super-resolution in X-ray projection radiography using deep neural network: Implementation on rotational angiography.

BACKGROUND: Rotational angiography acquires radiographs at multiple projection angles to demonstrate superimposed vasculature. However, this comes at the expense of the inherent risk of increased ionizing radiation. In this paper, building upon a successful deep learning model, we developed a novel technique to super-resolve the radiography at different projection angles to reduce the actual projections needed for a diagnosable radiographic procedure. METHODS: Ten models were trained for different levels of angular super-resolution (ASR), denoted as ASRN, where for every N+2 frames, the first and the last frames were submitted as inputs to super-resolve the intermediate N frames. RESULTS: The results show that large arterial structures were well preserved in all ASR levels. Small arteries were adequately visualized in lower ASR levels but progressively blurred out in higher ASR levels. Noninferiority of image quality was demonstrated in ASR1-4 (99.75% confidence intervals: -0.16-0.03, -0.19-0.04, -0.17-0.01, -0.15-0.05 respectively). CONCLUSIONS: ASR technique is capable of super-resolving rotational angiographic frames at intermediate projection angles.

Spectrum of neuroimaging mimics in children with COVID-19 infection.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has affected over 200 million people globally (including over 30 million people in the United States), with children comprising 12.9% of reported cases in the United States. In children, COVID-19 infection appears to be associated with mild respiratory symptoms; however, serious neurological complications may occur in conjunction with multisystem inflammatory syndrome. A wide spectrum of neurological diseases have been observed in children with COVID-19 infection including encephalitis, acute necrotizing encephalopathy, acute disseminated encephalomyelitis, cytotoxic lesion of the callosal splenium, posterior reversible encephalopathy syndrome, venous sinus thrombosis, vasculitis and infarction, Guillain-Barré syndrome, transverse myelitis, and myositis. This review describes the characteristic magnetic resonance neuroimaging features of these diseases and their differentiations from other imaging mimics. In addition, we review the possible pathophysiology underlying the association between these diseases and COVID-19-infection. As new SARS-CoV-2 variants emerge and COVID-19 infection continues to spread worldwide, pediatricians, radiologists, and first-line care givers should be aware of possible neurological diseases associated with COVID-19 infection when these reported neuroimaging patterns are observed in children during this pandemic.

Reduced Sleep Quality Is Related to Poor Quality of Life in Patients with Juvenile Myoclonic Epilepsy, a Case-Control Study.

Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy which is closely related to the sleep-wake cycle. This study aimed to investigate whether sleep disturbance is more common among patients with JME and the impact this may have on their quality of life (QOL). Thirty-four patients with JME and age- and gender-matched controls were recruited into this case control study, and assessed using validated sleep questionnaires including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Stanford Sleepiness Scale (SSS). QOL was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-31). The patients had a significantly higher PSQI score and higher proportion of abnormal PSQI scores than the controls. They also had higher ESS and SSS scores, but without statistical significance. The patients with poor sleep quality had significantly lower overall QOL, emotional well-being, and energy/fatigue subscale scores. The use of a higher number of antiseizure medications, dosage of levetiracetam, and usage of antiseizure medication polytherapy were associated with sleep disorders. Our results showed that sleep disturbance is common in patients with JME, and also that it has an impact on their QOL.

Multimodal Neural Evidence on the Corticostriatal Underpinning of Suicidality in Late-Life Depression.

BACKGROUND: Suicidality involves thoughts (ideations and plans) and actions related to self-inflicted death. To improve management and prevention of suicidality, it is essential to understand the key neural mechanisms underlying suicidal thoughts and actions. Following empirically informed neural framework, we hypothesized that suicidal thoughts would be primarily characterized by alterations in the default mode network indicating disrupted self-related processing, whereas suicidal actions would be characterized by changes in the lateral prefrontal corticostriatal circuitries implicating compromised action control. METHODS: We analyzed the gray matter volume and resting-state functional connectivity of 113 individuals with late-life depression, including 45 nonsuicidal patients, 33 with suicidal thoughts but no action, and 35 with past suicidal action. Between-group analyses revealed key neural features associated with suicidality. The functional directionality of the identified resting-state functional connectivity was examined using dynamic causal modeling to further elucidate its mechanistic nature. Post hoc classification analysis examined the contribution of the neural measures to suicide classification. RESULTS: As expected, reduced gray matter volumes in the default mode network and lateral prefrontal regions characterized patients with suicidal thoughts and those with past suicidal actions compared with nonsuicidal patients. Furthermore, region-of-interest analyses revealed that the directionality and strength of the ventrolateral prefrontal cortex-caudate resting-state functional connectivity were related to suicidal thoughts and actions. The neural features significantly improved classification of suicidal thoughts and actions over that based on clinical and suicide questionnaire variables. CONCLUSIONS: Gray matter reductions in the default mode network and lateral prefrontal regions and the ventrolateral prefrontal cortex-caudate connectivity alterations characterized suicidal thoughts and actions in patients with late-life depression.

Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults.

BACKGROUND AND OBJECTIVES: The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding the glymphatic system is inferred from rodent experiments and human research is limited. Our objective is to explore the associations between human glymphatic function, sleep, neuropsychological performance, and cerebral gray matter volumes. METHODS: This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on MRI. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function. RESULTS: A total of 84 participants (mean [SD] age 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized ß, -0.0025 [SE 0.0001]; p = 0.02), N2 sleep duration (unstandardized ß, 0.0002 [SE 0.0001]; p = 0.04), and the apnea-hypopnea index (unstandardized ß, -0.0011 [SE 0.0005]; p = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized ß, -0.59 [SE 0.28]; p = 0.04) and better CERAD-NB word list learning delayed recall subtest scores (unstandardized ß, 6.17 [SE 2.31]; p = 0.009) after covarying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized ß, 107.00 [SE 43.65]; p = 0.02) after controlling for age, sex, and total intracranial volume. DISCUSSION: Significant associations were identified between glymphatic function and sleep, stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performance, and cerebral gray matter volumes, suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders.