Periventricular Hyperintensities Research Articles

SERAC1 Deficiency- A New Phenotype.

Introduction - SERAC1 deficiency phenotype range from MEGD(H)EL syndrome, the most severe, to juvenile complicated spastic paraplegia, to adult-onset dystonic features (in only one patient). The MEGD(H)EL syndrome is characterized by (3-methylglutaconic aciduria with deafness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome). Biochemical abnormalities: elevated urinary 3 - metilglutaconic and 3-metilglutaric acids, high lactate and alanine in serum. Diagnosis is confirmed when biallelic pathogenic variants in SERAC1 gene are found. Brain MRI: basal ganglia lesions and generalized atrophy. Results/Case report - A 30-year-old patient with a moderate intellectual disability, developed, since the age of 25, a progressive loss of previous capacities (hand dexterity, oral language), and later subacute generalized dystonic features. Currently he has spastic tetraparesis, dystonia, scoliosis and autistic behavior, with bilateral basal ganglia lesions on brain MRI. Genetic study revealed biallelic pathogenic variants in SERAC1 gene, confirm MEGD(H)EL. A 73 years old patient with cognitive impairment and progressive spastic tetraparesis had multiple periventricular T2 hyperintense lesions. She has a homozygotic SERAC1 variant NM_032861: exon4:c.T139A: p.F471 (rs112780453), considered benign. Biochemical study revealed elevated plasmatic alanine and urinary3-metilglutaconic and 3-metilglutaric acid. This profile is concordant with mitochondrial dysfunction and SERAC1 Deficit. Conclusion - The first patient has the clinical symptoms associated to the MEGD(H)EL syndrome, and the biochemical and genetic confirmation of the diagnosis, without reservations. However, in the second patient, the progressive paraparesis and cognitive impairment did not appear to be caused by multiple sclerosis nor subcortical vascular leukoencephalopathy (without vascular risk factors). The abnormal biochemical profile is suggestive of SERAC1 Deficiency, even without genetic confirmation. In what should we believe?

Deep Medullary Vein and MRI Markers Were Related to Cerebral Hemorrhage Subtypes.

To explore the performance of deep medullary vein (DMV) and magnetic resonance imaging (MRI) markers in different intracerebral hemorrhage (ICH) subtypes in patients with cerebral small vessel disease (CSVD). In total, 232 cases of CSVD with ICH were included in this study. The clinical and image data were retrospectively analyzed. Patients were divided into hypertensive arteriopathy (HTNA)-related ICH, cerebral amyloid angiopathy (CAA)-related ICH, and mixed ICH groups. The DMV score was determined in the cerebral hemisphere contralateral to the ICH. The DMV score was different between the HTNA-related and mixed ICH groups (p < 0.01). The MRI markers and CSVD burden score were significant among the ICH groups (p < 0.05). Compared to mixed ICH, HTNA-related ICH diagnosis was associated with higher deep white matter hyperintensity (DWMH) (OR: 0.452, 95% CI: 0.253-0.809, p < 0.05) and high-degree perivascular space (PVS) (OR: 0.633, 95% CI: 0.416-0.963, p < 0.05), and CAA-related ICH diagnosis was associated with increased age (OR: 1.074; 95% CI: 1.028-1.122, p = 0.001). The DMV score correlated with cerebral microbleed (CMB), PVS, DWMH, periventricular white matter hyperintensity (PWMH), and CSVD burden score (p < 0.05) but not with lacuna (p > 0.05). Age was an independent risk factor for the severity of DMV score (OR: 1.052; 95% CI: 0.026-0.076, p < 0.001). DMV scores, CSVD markers, and CSVD burden scores were associated with different subtypes of ICH. In addition, DMV scores were associated with the severity of CSVD and CSVD markers.

The CADA-MRIT: An MRI Inventory Tool for Evaluating Cerebral Lesions in CADASIL Across Cohorts.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on MRI vary widely not only within families but also between different cohorts reported worldwide. Many limitations prevent comparison of imaging data obtained with different scanners and sequences in different patient cohorts. We aimed to develop and validate a simple tool to inventory quickly the key MRI features in CADASIL to compare imaging data across different populations. The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consists of 11 imaging items to assess periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (dPVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance, and time-effectiveness of CADA-MRIT were assessed using data from 3 independent patient cohorts. Imaging data from 671 patients with CADASIL (440 from France, 119 from Germany, and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, whereas CMB occurred in 83% of patients from the Asian cohort and in only 35% of European patients. CADA-MRIT scores obtained for WMH, CMB, and dPVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were from good to very good (weighted κ > 0.60). Global WMH and atrophy scores correlated strongly with accurate volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating 1 patient was approximately 2-3 minutes. The CADA-MRIT is an easy-to-use tool for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This instrument is reliable. It can be used with different imaging sequences or scanners. It also provides clinically relevant scores in a very short time for completion.

Effects of white matter hyperintensities on isolated executive function assessed by the Trail Making Test.

White matter hyperintensities (WMHs) on MRI are associated with cognitive dysfunction, particularly slow processing speed and executive dysfunction. However, it is not clear whether WMHs burden affects isolated executive function independent of aging when WMHs are assessed separately in periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH). To assess the relationship between the degree of WMHs and the performance on the Trail Making Test (TMT), which can evaluate isolated ability of set-shifting and working memory. 74 participants who visited our memory clinic and underwent the TMT subtests (TMT-A and TMT-B) and the Mini-Mental State Examination (MMSE). All subjects performed the TMT within the time limits and their MMSE scores were 24 or higher, and they were diagnosed as having normal cognition or mild cognitive impairment. The extent of PVH and DSWMH was graded from 0 to 3 using the Fazekas scale. We obtained testing time to complete the TMT-A and TMT-B, and calculated TMT-B minus TMT-A. We performed correlation analyses between the degree of WMHs and the time measures of the TMT subtests with adjustment of age. Average scores of the MMSE were not different among the groups either by PVH grade or by DSWMH grade. In contrast, average time required for the TMT-A, TMT-B, and TMT-B minus TMT-A increased along with exacerbation of PVH and DSWMH grade. After the adjustment of age we found significant association between only DSWMH grade and the time difference of TMT-B minus TMT-A. Exacerbation of PVH and DSWMH differentially affected isolated executive functions assessed by the TMT subtests independent of age and general cognitive function.

Imaging Spectrum of Neurological Manifestations of Hemophagocytic Lymphohistiocytosis in Pediatrics: A Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon condition, which can result either from a primary genetic abnormality affecting children or secondary to various conditions like malignancy or infection predominantly in adults. HLH is associated with immune dysregulation, resulting in an uncontrolled overproduction and infiltration of lymphocytes and histiocytes. The infiltration predominantly involves liver, spleen, lymph nodes, and central nervous system. Neuroimaging features on magnetic resonance imaging are highly nonspecific and variable. The most typical findings include periventricular white matter hyperintensities and diffuse atrophy. Ring or nodular enhancing or nonenhancing focal parenchymal lesions may be seen. Here, we present three pediatric cases of primary HLH with a wide spectrum of imaging findings involving cerebral and cerebellar cortex, white matter, deep gray matter, and brain stem. The findings in these patients range from small nonenhancing hemorrhagic lesions and enhancing small lesions to ill-defined mass with mass effect and midline shift. Lesions in deep gray matter including thalamus, basal ganglia, and also brain stem in HLH are rarely described in literature. Early diagnosis of HLH and timely management can improve the course of the disease.

Striatal Dopamine Transporter Uptake, Parkinsonism, and Cognition in Alzheimer's Disease.

The correlates of motor parkinsonism in Alzheimer's disease (AD) remains controversial. We evaluated the effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD. This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET, 18 F-Florbetaben PET, 3-Tesla brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal, and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen, and substantia nigra were quantified. We investigated the relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score, and cognition using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. Path analysis and multivariable GLM for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Association between National Institutes of Health Stroke Scale and Functional Independence Measure scores in patients with ischemic stroke from convalescent rehabilitation outcomes.

We investigated the associations among neurological severity, activities of daily living (ADLs), and clinical factors in patients with ischemic stroke in convalescent rehabilitation outcome. The study sample included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years) for inpatient convalescent rehabilitation. National Institutes of Health Stroke Scale (NIHSS) was used to measure the neurological severity, and Functional Independence Measure (FIM) was used to assess ADLs at discharge. Leukoaraiosis was graded based on periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on magnetic resonance imaging. The correlations between NIHSS scores and total FIM scores were significant but relatively mild (r = -0.684, P < 0.001). Multiple regression analysis revealed that age and PVH grade significantly decreased their total FIM scores and affected the discrepancies between NIHSS scores at discharge (P < 0.001), but DWMH scores did not affect these results. Factors such as positive history of heart disease (P = 0.008) and bilateral infarction (P = 0.038) additionally decreased their total FIM scores and affected the discrepancies between NIHSS scores. These findings suggest that age, PVH, history of heart disease positive, and bilateral infarction in patients with ischemic stroke affected their performance of ADLs and the discrepancies between their neurological severities in convalescent rehabilitation outcomes, probably because the pathophysiological background of leukoaraiosis and these factors strongly decrease their ADL performance in post-phase ischemic stroke.

Relationship between Serum Irisin Levels and MRI-Measured Cerebral Small Vessel Disease in Japanese Men.

Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0-4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41-0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

The Positional Relationship between Lacunae and White Matter Hyperintensity in Patients with Cerebral Small Vessel Disease.

Lacunae and white matter hyperintensity (WMH) are two crucial imaging biomarkers of cerebral small vessel disease (CSVD). Multiple studies have revealed a close relationship between WMH and lacunae and found that a double penumbra existed at the edge of WMH that affects lacunae formation. The study aimed to explore the spatial distribution characteristics and possible influencing factors of lacuna in relation to white matter hyperintensity in patients with CSVD. A total of 480 CSVD patients with WMH and with or without lacunae were included. Data about blood biochemical indicators, cerebrovascular CT angiography, 24-hour ambulatory blood pressure and ambulatory electrocardiogram, brain magnetic resonance imaging, and transcranial Doppler ultrasound were gathered from all subjects. They were categorised into four groups based on the spatial interaction between lacunae and WMH. Univariate analyses and multiple logistic regression analyses were used to compare the differences in traditional vascular risk factors, heart rate and blood pressure indicators, arterial pulsatility index (PI) values, and arterial stenosis among different groups. The average age of 480 patients was (58.63 ± 11.91) years, with 347 males (72.3%). Univariate analysis indicated that age, fasting blood glucose, triglycerides, total cholesterol, highdensity lipoprotein, 24-hour and daytime and night systolic and diastolic blood pressure, nocturnal heart rate, heart rate variability, PI values of ipsilateral and contralateral MCA (middle cerebral artery) and ICA (Internal carotid artery) of the lacunae, Fazekas score of PWMH (periventricular white matter hyperintensities), the proportion of MCA or ICA with stenosis rate over 50% on the ipsilateral side of the lacunae were significantly different between different groups (p < 0.05). High fasting blood glucose (OR=1.632, 95% CI= (1.128, 2.361), p =0.009), (OR=1.789, 95%CI= (1.270, 2.520), p = 0.001), (OR=1.806, 95% CI= (1.292, 2.524), p =0.001) was identified as a risk factor for lacunae formation by logistic regression analysis. High fasting blood glucose can be considered a risk factor for lacunae formation in patients with WMH. The more severe the PWMH and the higher the nocturnal heart rate, the more likely the lacunae, as well as PWMH, overlap completely. Ipsilateral arteriosclerosis and stenosis are independent risk factors for no contact between lacunae and PWMH.

The Early Postoperative Course of Cognitive Function and Preoperative Cerebrovascular Reserve.

Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors. Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI. COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores (R 2 = 0.415; p = 0.0017). Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery.

Correlation between neutrophil gelatinase phase lipocalin and cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.

White matter hyperintensities: a possible link between sarcopenia and cognitive impairment in patients with mild to moderate Alzheimer's disease.

Alzheimer's disease (AD) has been reported to be associated with sarcopenia. White matter hyperintensities (WMH) are common in AD patients. However, the effect of WMH on sarcopenia in AD remains unclear. We hence aimed to investigate the possible association between regional WMH volumes and sarcopenic parameters in AD. 57 mild to moderate AD patients and 22 normal controls (NC) were enrolled. Sarcopenic parameters were assessed, including appendicular skeletal mass index (ASMI), grip strength, 5-times sit-to-stand (5-STS) time, and gait speed. The volumes of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) were quantified using 3D-slicer software. AD subjects exhibited a lower ASMI, a slower gait speed, an increased 5-STS time, and larger volumes of PVH and DWMH than those in the NC group. In AD subjects, total WMH and PVH volumes were related to cognitive impairment, particularly executive function decline. Moreover, total WMH volume and PVH volume were negatively correlated with gait speed across various clinical stages of AD. Multiple linear regression analysis showed that PVH volume was independently associated with 5-STS time and gait speed, whereas DWMH volume was only independently associated with gait speed. WMH volume was associated with cognitive decline and various sarcopenic parameters. It thereby suggested that WMH may serve as the connection between sarcopenia and cognitive dysfunction in AD. Further studies are needed to confirm these findings and to determine whether sarcopenia interventions reduce WMH volume and improve cognitive function in AD.

White matter lesions predominantly located in deep white matter represent embolic etiology rather than small vessel disease

AbstractBackgroundIndividuals with cerebral small vessel disease (CSVD) usually have both periventricular and deep white matter hyperintensities (dpWMH). However, we often encounter individuals whose WMH lesions are mainly located in the corticomedullary or deep white matter with minimal periventricular WMHs (dWMH). We aimed to determine if the dWMH pattern could be attributed to embolic etiologies.MethodsWe retrospectively recruited participants who had undergone comprehensive dementia evaluation, agitated saline contrast echocardiography, and brain MRI. The participants were classified into two groups according to WMH distributions, the dWMH (WMHs in deep and corticomedullary area, with minimal periventricular WMHs) and the dpWMH (mainly periventricular WMHs with or without deep WMHs) groups. We hypothesized that dWMH is more likely associated with embolism, whereas dpWMH with CSVD. We compared the clinical characteristics, WMH distributions, and the positive rate of agitated saline study between the two groups.ResultsOf the 90 participants, 27 fulfilled the dWMH criteria and 12 met the dpWMH criteria. The dWMH group was younger (62.2±7.5 vs 78.9±7.3, p&lt;0.001), and had a lower prevalence of hypertension (29.6% vs. 75%, p = 0.008), DM (3.7% vs. 25%, p = 0.043), and hyperlipidemia (33.3% vs. 83.3%, p = 0.043) than the dpWMH group. Regarding deep white matter lesions, the number of small lesions (&lt;3 mm) was higher in the dWMH (10.9±9.7) than the dpWMH (3.1±6.4) group (p = 0.008), and WMHs were predominantly distributed in border‐zones of major cerebral arteries and corticomedullary areas.Most importantly, the positive rate of agitated saline was higher in the dWMH than the dpWMH group (81.5% vs. 33.3%, p = 0.003).ConclusionsThe dWMH group with younger age, fewer cardiovascular risk factors showed more border‐zone distributions, and higher positivity of agitated saline test than dpWMH group, indicating that WMH distributions mainly in the corticomedullary or deep area with minimal periventricular WMH lesions suggest embolic etiologies.

1002 Bilateral Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) in a Patient with Obstructive Sleep Apnea (OSA)

Abstract Introduction Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is an ischemic insult to the anterior portion of the optic nerve with unclear etiology. Several small sized studies and case reports have demonstrated association between OSA and NAION. In this case, we present a patient with bilateral NAION who was later diagnosed with OSA which may signify this important clinical association. Report of case(s) A 57-year-old man with history of hypertension, presented to the ophthalmology clinic for sudden painless decreased visual acuity of the right eye for one-month duration. He had no history of head trauma or other neurological deficits on his initial presentation. He reported having “bad vision” in his left eye for the entire of his life. Funduscopic evaluation revealed bilateral optic disc edema more in the left eye. Laboratory workup including CBC, CMP and HbA1C were within normal limits. Brain MRI showed only mild nonspecific scattered subcortical and deep periventricular hyperintensities suggestive of chronic small vessel ischemic disease and no acute infarct or masses. MRI of the orbits was normal. A diagnosis of bilateral Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) was highly suggested based on the clinical history and examination findings. A referral to a sleep clinic was made to evaluate for possible sleep apnea. A polysomnogram confirmed obstructive sleep apnea with AHI of 7.2/h, REM AHI of 7.7/h and supine AHI 14.9/h. Nocturnal hypoxemia associated with the respiratory events with time of O2 saturation &amp;lt; 88% for 29 minutes. Patient was referred for a titration study to determine the appropriate PAP pressure to treat his sleep disordered breathing. Conclusion This case adds to the current evolving evidence of the link between OSA with NAION. It signifies the importance of having an index of suspicion, among both sleep specialists and ophthalmologists, to recognize patients who may have one of the conditions and consider screening for the other, which may lead to earlier diagnosis and improved outcomes. Support (if any)

A multiphysics model to predict periventricular white matter hyperintensity growth during healthy brain aging

Periventricular white matter hyperintensities (WMH) are a common finding in medical images of the aging brain and are associated with white matter damage resulting from cerebral small vessel disease, white matter inflammation, and a degeneration of the lateral ventricular wall. Despite extensive work, the etiology of periventricular WMHs remains unclear. We pose that there is a strong coupling between age-related ventricular expansion and the degeneration of the ventricular wall which leads to a dysregulated fluid exchange across this brain–fluid barrier. Here, we present a multiphysics model that couples cerebral atrophy-driven ventricular wall loading with periventricular WMH formation and progression. We use patient data to create eight 2D finite element models and demonstrate the predictive capabilities of our damage model. Our simulations show that we accurately capture the spatiotemporal features of periventricular WMH growth. For one, we observe that damage appears first in both the anterior and posterior horns and then spreads into deeper white matter tissue. For the other, we note that it takes up to 12 years before periventricular WMHs first appear and derive an average annualized periventricular WMH damage growth rate of 15.2 ± 12.7mm2/year across our models. A sensitivity analysis demonstrated that our model parameters provide sufficient sensitivity to rationalize subject-specific differences with respect to onset time and damage growth. Moreover, we show that the septum pellucidum, a membrane that separates the left and right lateral ventricles, delays the onset of periventricular WMHs at first, but leads to a higher WMH load in the long-term.Statement of Significance: Brain aging is accompanied by many structural and functional changes. In nearly all aged brains, white matter lesions appear in periventricular and diffuse subcortical regions which are associated with progressive functional decline. In our work, we present a multiphysics model that not only predicts the onset location of periventricular white matter lesions but also their subsequent growth as a result of age-related cerebral atrophy and ventricular enlargement. Our model provides a mechanics-based rationale for their characteristic spatiotemporal progression patterns and will allow to identify at-risk subjects for early lesion formation.

MRI Assessment of Brain Frailty and Clinical Outcome in Patients With Acute Posterior Perforating Artery Infarction.

Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. Prospective. One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. 3 TECHNICAL EFFICACY: Stage 3.

Neurological and imaging phenotypes of adults with untreated phenylketonuria: new cases and literature review.

Phenylketonuria (PKU) is the most prevalent congenital disease of amino acid metabolism. Neurological manifestations usually complicate PKU in untreated adult patients. This study describes neurological and imaging phenotypes of adult patients with untreated PKU. We investigated a cohort of 320 unrelated adult patients with suspected genetic leukoencephalopathies using whole-exome sequencing (WES). We analyzed the phenotypic features of adult PKU patients in our cohort and summarized cases reported in the literature. We identified 10 patients in our cohort and 12 patients in the literature, who presented with neurological manifestations and were diagnosed with PKU in adulthood. Approximately 60% of these patients had onset of clinical features in adulthood. The most common neurological symptoms of patients presenting in adulthood were cognitive disturbance and spastic paralysis, followed by vision loss, cerebellar ataxia, weakness of limbs, and seizure. This differed from that of patients presenting with PKU features in childhood, who consistently had mental retardation with various neurological complications emerging during a broad age range. Imaging findings were similar between patients presenting with clinical features in childhood compared with adulthood, comprising symmetric periventricular white matter hyperintense on T2-weighted imaging and diffusion-weighted imaging predominantly in the parietal and occipital lobes. Also, normal brain imaging and diffuse leukoencephalopathies were observed in both patient groups. PKU with clinical features presenting in adulthood is an atypical subtype and should be considered during diagnosis of adults with neurological symptoms and leukoencephalopathy. DWI seems to be most helpful to distinguish patients with PKU. Additionally, we demonstrate that PKU constitutes a part (3.1%) of adult genetic leukoencephalopathies.

A Fully Automated Visual Grading System for White Matter Hyperintensities of T2-Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. The Krippendorff's alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

White matter hyperintensities burden in the frontal regions is positively correlated to the freezing of gait in Parkinson's disease.

Previous studies have reported that white matter hyperintensities (WMHs) are associated with freezing of gait (FOG), but it is not clear whether their distribution areas have correlations with FOG in Parkinson's disease (PD) and the potential influencing factors about WMHs. Two hundred and forty-six patients with PD who underwent brain MRI were included. Participants were divided into PD with FOG (n = 111) and PD without FOG (n = 135) groups. Scheltens score was used to assess the WMHs burden in the areas of deep white matter hyperintensities (DWMHs), periventricular hyperintensities (PVHs), basal ganglia hyperintensities (BGHs), and infratentorial foci of hyperintensities (ITF). Whole brain WMHs volume was evaluated by automatic segmentation. Binary logistic regression was used to evaluate relationships between WMHs and FOG. The common cerebrovascular risk factors that may affect WMHs were evaluated by mediation analysis. There were no statistical differences between PD with and without FOG groups in whole brain WMHs volume, total Scheltens score, BGHs, and ITF. Binary logistic regression showed that the total scores of DWMHs (OR = 1.094; 95% CI, 1.001, 1.195; p = 0.047), sum scores of PVHs and DWMHs (OR = 1.080; 95% CI, 1.003, 1.164; p = 0.042), especially the DWMHs in frontal (OR = 1.263; 95% CI, 1.060, 1.505 p = 0.009), and PVHs in frontal caps (OR = 2.699; 95% CI, 1.337, 5.450; p = 0.006) were associated with FOG. Age, hypertension, and serum alkaline phosphatase (ALP) are positively correlated with scores of DWMHs in frontal and PVHs in frontal caps. These results indicate that WMHs distribution areas especially in the frontal of DWMHs and PVHs play a role in PD patients with FOG.