Eif2b3 mutants recapitulate phenotypes of vanishing white matter disease and validate novel disease alleles in zebrafish.

Leukodystrophy with vanishing white matter (VWM), also called Childhood Ataxia with Central Nervous System Hypomyelination, is caused by mutations in the subunits of the eukaryotic translation initiation factor, EIF2B1, EIF2B2, EIF2B3, EIF2B4 or EIF2B5. However, little is known regarding the underlying pathogenetic mechanisms, and there is no curative treatment for VWM. In this study, we established the first EIF2B3 animal model for VWM disease in vertebrates by CRISPR mutagenesis of the highly conserved zebrafish ortholog eif2b3. Using CRISPR, we generated two mutant alleles in zebrafish eif2b3, 10- and 16-bp deletions, respectively. The eif2b3 mutants showed defects in myelin development and glial cell differentiation, and increased expression of genes in the induced stress response pathway. Interestingly, we also found ectopic angiogenesis and increased VEGF expression. Ectopic angiogenesis in the eif2b3 mutants was reduced by the administration of VEGF receptor inhibitor SU5416. Using the eif2b3 mutant zebrafish model together with in silico protein modeling analysis, we demonstrated the pathogenicity of 18 reported mutations in EIF2B3, as well as of a novel variant identified in a 19-month-old female patient: c.503 T > C (p.Leu168Pro). In summary, our zebrafish mutant model of eif2b3 provides novel insights into VWM pathogenesis and offers rapid functional analysis of human EIF2B3 gene variants.

Temporal Profile of Blood-Brain Barrier Breakdown in Reversible Cerebral Vasoconstriction Syndrome.

Background and Purpose- Reversible cerebral vasoconstriction syndrome (RCVS) has a unique temporal course of vasoconstriction. Blood-brain barrier (BBB) breakdown is part of the pathophysiology of RCVS, but its temporal course is unknown. We aimed to investigate the temporal profile of BBB breakdown and relevant clinical profiles in a large sample size. Methods- In this prospective observatory bicenter study, patients who underwent contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging within 2 months from onset were included. The presence and extent of BBB breakdown were evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. Contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging data were analyzed using a semiautomated segmentation technique to quantitatively measure the area of Gadolinium leakage into cerebrospinal fluid space. The univariable and multivariable linear regressions were performed to investigate the independent effect of time from onset with adjustment for other covariates. Results- In the 186 patients with angiogram-proven RCVS included in this analysis, BBB breakdown was observed in 52.6%, 56.8%, 30.3%, 40.0%, and 23.8% in the first, second, third, fourth, and ≥fifth week after onset. The extent of BBB breakdown peaked at first and second week, whereas the peak of vasoconstriction was observed at the third week after onset. Multivariable analysis showed the second week from onset (ß, 3.35 [95% CI, 0.07-6.64]; P=0.046) and blood pressure surge (ß, 3.84 [95% CI, 1.75-5.92]; P<0.001) were independently associated with a greater extent of BBB breakdown. A synergistic effect of time from onset and blood pressure surge was found (P for interaction=0.006). Conclusions- Frequency and extent of BBB breakdown are more prominent during the early stage in patients with RCVS, with an earlier peak than that of vasoconstriction. The temporal course of BBB breakdown may provide a pathophysiologic background of the temporal course of neurological complications of RCVS.

Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging study (STAMINA-MRI Study).

OBJECTIVE: Intracranial atherosclerosis is a major cause of ischaemic stroke worldwide. A number of studies have shown the effects of statin treatment on coronary and carotid artery plaques, but there is little evidence on the effects of statin treatment on intracranial atherosclerotic plaques. METHODS: The Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis - High-Resolution Magnetic Resonance Imaging (STAMINA-MRI) Trial is a single-arm, prospective, observational study monitoring imaging and clinical outcomes of high-dose statin treatment among statin-naive patients with acute ischaemic stroke caused by symptomatic intracranial atherosclerosis. The primary outcome was the change in vascular remodelling and plaque characteristics before and after 6 months (median: 179 days, IQR 163-189 days) of statin treatment measured by high-resolution MRI (HR-MRI). RESULTS: A total of 77 patients (mean age: 62.6±13.7 years, 61.0% women) were included in this study. Low-density lipoprotein cholesterol (LDL-C) levels (mg/dL) at initial and follow-up assessments were 125.81±35.69 and 60.95±19.28, respectively. Overall, statin treatment significantly decreased enhancement of plaque volume (mm3, 32.07±39.15 vs 17.06±34.53, p=0.013), the wall area index (7.50±4.28 vs 5.86±4.05, p=0.016) and stenosis degree (%, 76.47±20.23 vs 64.05±21.29, p<0.001), but not the remodelling index (p=0.195). However, 35% patients showed no change or increased enhancement volume and stenosis degree after statin treatment. Higher reduction of LDL-C and longer duration of statin treatment were associated with decreased enhancement volume after statin treatment. CONCLUSIONS: High-dose statin treatment effectively stabilised symptomatic intracranial atherosclerotic plaques as documented by HR-MRI. Further study is needed to determine laboratory and genetic factors associated with poor response to statins and alternative therapeutic options, such as proprotein convertase subtilisin-kexin type 9 inhibitors, for these patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02458755.

Data-driven synthetic MRI FLAIR artifact correction via deep neural network.

BACKGROUND: FLAIR (fluid attenuated inversion recovery) imaging via synthetic MRI methods leads to artifacts in the brain, which can cause diagnostic limitations. The main sources of the artifacts are attributed to the partial volume effect and flow, which are difficult to correct by analytical modeling. In this study, a deep learning (DL)-based synthetic FLAIR method was developed, which does not require analytical modeling of the signal. PURPOSE: To correct artifacts in synthetic FLAIR using a DL method. STUDY TYPE: Retrospective. SUBJECTS: A total of 80 subjects with clinical indications (60.6 ± 16.7 years, 38 males, 42 females) were divided into three groups: a training set (56 subjects, 62.1 ± 14.8 years, 25 males, 31 females), a validation set (1 subject, 62 years, male), and the testing set (23 subjects, 57.3 ± 20.4 years, 13 males, 10 females). FIELD STRENGTH/SEQUENCE: 3 T MRI using a multiple-dynamic multiple-echo acquisition (MDME) sequence for synthetic MRI and a conventional FLAIR sequence. ASSESSMENT: Normalized root mean square (NRMSE) and structural similarity (SSIM) were computed for uncorrected synthetic FLAIR and DL-corrected FLAIR. In addition, three neuroradiologists scored the three FLAIR datasets blindly, evaluating image quality and artifacts for sulci/periventricular and intraventricular/cistern space regions. STATISTICAL TESTS: Pairwise Student's t-tests and a Wilcoxon test were performed. RESULTS: For quantitative assessment, NRMSE improved from 4.2% to 2.9% (P < 0.0001) and SSIM improved from 0.85 to 0.93 (P < 0.0001). Additionally, NRMSE values significantly improved from 1.58% to 1.26% (P < 0.001), 3.1% to 1.5% (P < 0.0001), and 2.7% to 1.4% (P < 0.0001) in white matter, gray matter, and cerebral spinal fluid (CSF) regions, respectively, when using DL-corrected FLAIR. For qualitative assessment, DL correction achieved improved overall quality, fewer artifacts in sulci and periventricular regions, and in intraventricular and cistern space regions. DATA CONCLUSION: The DL approach provides a promising method to correct artifacts in synthetic FLAIR. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1413-1423.

A case report of isolated orbital vasculitis mimicking retinal migraine: A potential cause of recurrent transient monocular blindness and ipsilateral headache.

BACKGROUND: Retinal migraine is an important differential diagnosis of recurrent transient monocular blindness accompanied by headache when other etiologies are excluded. Here, we report a case of orbital vasculitis which initially mimicked retinal migraine. CASE REPORT: A 47-year-old woman had recurrent episodes of fully reversible transient monocular blindness accompanied by ipsilateral headache for 15 months. The patient's neuroimaging and cardiac and ophthalmologic evaluations were normal. With a diagnosis of retinal migraine, her symptoms remitted in response to prophylactic treatment with topiramate and propranolol for 8 months. Three months after discontinuation of medications, transient monocular blindness recurred. High-resolution vessel wall magnetic resonance imaging revealed enhancement of the ipsilateral orbital vessels. Isolated orbital vasculitis was diagnosed. Complete remission of transient monocular blindness was achieved after steroid pulse therapy. DISCUSSION: Isolated orbital vasculitis should be considered in differential diagnosis of recurrent transient monocular blindness and ipsilateral headache. High-resolution vessel wall magnetic resonance imaging can be helpful for the diagnosis.

Cav-1 (Caveolin-1) and Arterial Remodeling in Adult Moyamoya Disease.

Background and Purpose- Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that cav-1 (caveolin-1)-a protein that controls the regulation of endothelial vesicular trafficking and signal transduction-is associated with negative remodeling in MMD. Methods- We prospectively recruited 77 consecutive patients with MMD diagnosed via conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. The outer distal ICA diameters were examined using high-resolution magnetic resonance imaging. We evaluated whether the degree of negative remodeling in the patients with MMD was associated with RNF213 polymorphism, cav-1 levels, or various clinical and vascular risk factors. We also investigated whether the derived factor was associated with negative remodeling at the cellular level using the tube formation and apoptosis assays. Results- The serum cav-1 level was lower in the patients with MMD than in the controls (0.47±0.29 versus 0.86±0.68 ng/mL; P=0.034). The mean ICA diameter was 2.48±0.98 mm for the 126 affected distal ICAs in patients with MMD and 3.84±0.42 mm for the asymptomatic ICAs in the controls ( P<0.001). After adjusting for confounders, cav-1 levels (coefficient, 1.018; P<0.001) were independently associated with the distal ICA diameter in patients with MMD. In vitro analysis showed that cav-1 downregulation suppressed angiogenesis in the endothelial cells and induced apoptosis in the smooth muscle cells. Conclusions- Our findings suggest that cav-1 may play a major role in negative arterial remodeling in MMD.

Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis.

OBJECTIVE: Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood-brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology-based diagnosis of RCVS. METHODS: We prospectively recruited 72 consecutive patients with thunderclap headache who did not have aneurysmal subarachnoid hemorrhage from April 2015 to July 2016 at the Samsung Medical Center. Based on the International Classification of Headache Disorders-3 beta criteria and neuroimaging, patients were classified as having RCVS (n = 41; "definite" in 29 imaging-proven patients and "probable" in 12 imaging-negative patients), other secondary causes (n = 7), and thunderclap headache of undetermined cause (n = 24). BBB breakdown was evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. RESULTS: BBB breakdown was documented in 20 (69.0%) patients with definite RCVS, 3 (25.0%) patients with probable RCVS, and none with other secondary causes. BBB breakdown was present in RCVS patients with (n = 4) and without (n = 19) concomitant posterior reversible encephalopathy syndrome. In patients with RCVS, the extent of BBB breakdown was independently associated with neurological complications (multivariate odds ratio = 1.48 per 1 territorial increase, 95% confidence interval = 1.04-2.12, adjusted p = 0.032). Three (12.5%) patients with thunderclap headache of undetermined cause were newly classified as having RCVS by the presence of BBB breakdown. INTERPRETATION: This is the first study to show BBB breakdown in patients with RCVS. This finding might broaden our understanding of the pathophysiology and clinical spectrum of RCVS. Ann Neurol 2017;81:454-466.

Intracranial structural alteration predicts treatment outcome in patients with spontaneous intracranial hypotension.

Background Intracranial structural dislocation in spontaneous intracranial hypotension (SIH) can be measured by various intracranial angles and distances. We aimed to identify the clinical significance of structural dislocation in relation to treatment outcome in patients with SIH. Methods In this retrospective analysis, we identified patients with SIH who received an epidural blood patch (EBP) at Samsung Medical Center from January 2005 to March 2015. Structural dislocation in pretreatment MRIs of SIH patients was assessed by measuring tonsillar herniation, mamillopontine distance, the angle between the vein of Galen and straight sinus (vG/SS angle), the pontomesencephalic angle, and the lateral ventricular angle. After the first EBP, poor response was defined as the persistence of symptoms that prompted a repeat EBP. Results Out of the 95 patients included, 31 (32.6%) showed poor response. Among the radiological markers of structural dislocation, the vG/SS angle was associated with poor response (49.82 ± 16.40° vs 66.58 ± 26.08°, p = 0.002). Among clinical variables, premorbid migraine ( p = 0.036) was related to poor response. In multivariate analysis, reduced vG/SS angle was independently associated with poor response (OR 1.04 [95% CI 1.01 - 1.07] per 1° decrease, p = 0.006). In 23 patients who underwent MRI after successful treatment, the vG/SS angle significantly increased after the EBP ( p < 0.001, by paired t-test), while two patients with aggravation or recurrence showed a further reduction of their vG/SS angles. Conclusions Intracranial structural dislocation, measured by the vG/SS angle, is associated with poor response to the first EBP in patients with SIH. Successful treatment can reverse the structural dislocation.

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats.

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel-based analysis are highly dependent on the user-hypothesis and parameter settings for implementation. In contrast, tract-based spatial statistics (TBSS) allows for reliable voxel-wise analysis via the projection of diffusion-derived parameters onto an alignment-invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI-derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2-4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post-stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post-stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo-normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.

Granulomatosis With Polyangiitis-Associated Hypertrophic Pachymeningitis Mimicking Spontaneous Intracranial Hypotension: A Case Report.

BACKGROUND: Dural enhancement is a characteristic finding in both spontaneous intracranial hypotension and hypertrophic pachymeningitis. Positional headache is the most important feature that distinguishes the two diseases. We report a patient with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) who initially manifested like spontaneous intracranial hypotension. CASE PRESENTATION: We report here the case of a 63-year old man who presented with severe positional headache. The patient had typical symptoms, symmetric dural enhancement, and a recent history of nontraumatic subdural hygroma which led to the diagnosis of spontaneous intracranial hypotension, but was finally diagnosed as granulomatosis with polyangiitis-associated secondary hypertrophic pachymeningitis. Cyclophosphamide therapy was effective for the maintenance of remission. CONCLUSIONS: Hypertrophic pachymeningitis associated with granulomatosis with polyangiitis can present with positional headache and subdural hygroma, mimicking spontaneous intracranial hypotension. Granulomatosis with polyangiitis should be suspected when patients with spontaneous intracranial hypotension or hypertrophic pachymeningitis show atypical features.

Dual-energy CT with virtual monochromatic images and metal artifact reduction software for reducing metallic dental artifacts.

Background Metallic dental prostheses may degrade image quality on head and neck computed tomography (CT). However, there is little information available on the use of dual-energy CT (DECT) and metal artifact reduction software (MARS) in the head and neck regions to reduce metallic dental artifacts. Purpose To assess the usefulness of DECT with virtual monochromatic imaging and MARS to reduce metallic dental artifacts. Material and Methods DECT was performed using fast kilovoltage (kV)-switching between 80-kV and 140-kV in 20 patients with metallic dental prostheses. CT data were reconstructed with and without MARS, and with synthesized monochromatic energy in the range of 40-140-kiloelectron volt (keV). For quantitative analysis, the artifact index of the tongue, buccal, and parotid areas was calculated for each scan. For qualitative analysis, two radiologists evaluated 70-keV and 100-keV images with and without MARS for tongue, buccal, parotid areas, and metallic denture. The locations and characteristics of the MARS-related artifacts, if any, were also recorded. Results DECT with MARS markedly reduced metallic dental artifacts and improved image quality in the buccal area ( P < 0.001) and the tongue ( P < 0.001), but not in the parotid area. The margin and internal architecture of the metallic dentures were more clearly delineated with MARS ( P < 0.001) and in the higher-energy images than in the lower-energy images ( P = 0.042). MARS-related artifacts most commonly occurred in the deep center of the neck. Conclusion DECT with MARS can reduce metallic dental artifacts and improve delineation of the metallic prosthesis and periprosthetic region.

CT, MRI, and 18F-FDG PET/CT findings of malignant peripheral nerve sheath tumor of the head and neck.

Background Malignant peripheral nerve sheath tumor (MPNST) is a highly malignant tumor and rarely occurs in the head and neck. Purpose To describe the imaging features of MPNST of the head and neck. Material and Methods We retrospectively analyzed computed tomography (CT; n = 14), magnetic resonance imaging (MRI; n = 16), and 18F-FDG PET/CT (n = 5) imaging features of 18 MPNSTs of the head and neck in 17 patients. Special attention was paid to determine the nerve of origin from which the tumor might have arisen. Results All lesions were well-defined (n = 3) or ill-defined (n = 15) masses (mean, 6.1 cm). Lesions were at various locations but most commonly the neck (n = 8), followed by the intracranial cavity (n = 3), paranasal sinus (n = 2), and orbit (n = 2). The nerve of origin was inferred for 11 lesions: seven in the neck, two in the orbit, one in the cerebellopontine angle, and one on the parietal scalp. Attenuation, signal intensity, and enhancement pattern of the lesions on CT and MRI were non-specific. Necrosis/hemorrhage/cystic change within the lesion was considered to be present on images in 13 and bone change in nine. On 18F-FDG PET/CT images, all five lesions demonstrated various hypermetabolic foci with maximum standard uptake value (SUVmax) from 3.2 to 14.6 (mean, 7.16 ± 4.57). Conclusion MPNSTs can arise from various locations in the head and neck. Though non-specific, a mass with an ill-defined margin along the presumed course of the cranial nerves may aid the diagnosis of MPSNT in the head and neck.

Previous Statin Use and High-Resolution Magnetic Resonance Imaging Characteristics of Intracranial Atherosclerotic Plaque: The Intensive Statin Treatment in Acute Ischemic Stroke Patients With Intracranial Atherosclerosis Study.

BACKGROUND AND PURPOSE: Although statin use has been linked to the stabilization of systemic atherosclerosis, its effect on symptomatic intracranial atherosclerotic plaques has yet to be explored. We hypothesized that premorbid statin use is associated with plaque instability in intracranial arteries and may lead to differential patterns (size and distribution) of ischemic lesions in patients with acute intracranial atherosclerotic stroke. METHODS: One hundred and thirty-six patients with acute infarcts caused by intracranial atherosclerotic stroke underwent high-resolution magnetic resonance imaging. Patients were categorized into 3 groups based on their premorbid statin use: nonuser, low-dose user, and high-dose user, according to the 2013 American College of Cardiology/American Heart Association guidelines on blood cholesterol. Symptomatic lesions in intracranial arteries were analyzed using high-resolution magnetic resonance imaging for vascular morphology (degree of stenosis, remodeling index, and wall index) and plaque activation (pattern and volume of enhancement). The cortical distribution and volume of ischemic brain lesions were measured using diffusion-weighted imaging. RESULTS: Among the enrolled patients, 38 (27.94%) were taking statins before the index stroke (22 low-dose statins and 16 high-dose statins). The degree of stenosis, remodeling index, and wall index did not differ between the 3 groups. However, the volume of plaque enhancement was significantly lower in statin users (nonuser, 33.26±40.72; low-dose user, 13.15±17.53; high-dose user, 3.13±5.26; P=0.002). Premorbid statin use was associated with a higher prevalence of nonembolic stroke and a decrease in large cortical infarcts (P=0.012). CONCLUSIONS: Premorbid statin usage is independently associated with reduced plaque enhancement and a decrease in large cortical lesions in patients with intracranial atherosclerotic stroke.

Echoing Plaque Activity of the Coronary and Intracranial Arteries in Patients With Stroke.

BACKGROUND AND PURPOSE: Atherosclerosis is a systemic disease, and both coronary and intracranial atherosclerosis are common in the elderly. Unlike coronary artery disease (CAD), intracranial atherosclerotic disease can cause intracranial atherosclerotic stroke by branch occlusive disease (B-type) and coronary-type rupture of plaque (C-type). We hypothesized that plaque characteristics of intracranial arteries are associated with those of coronary arteries. METHODS: Eighty-one patients with acute cerebral infarcts caused by intracranial atherosclerotic disease without history of CAD were analyzed. Asymptomatic CAD burden (number and degree of stenosis) and plaque characteristics (calcified, mixed, and noncalcified) were measured with multidetector computed tomography, whereas the asymptomatic intracranial atherosclerotic disease burden was measured using magnetic resonance angiography. The symptomatic intracranial artery was analyzed using high-resolution magnetic resonance imaging for vascular morphology (stenosis degree, remodeling index, and wall index) and plaque activation (enhancement pattern and volume). RESULTS: The asymptomatic CAD burden was correlated with the asymptomatic intracranial atherosclerotic disease burden. The overall CAD burden did not differ between B- and C-type intracranial atherosclerotic stroke. However, the prevalence of noncalcified coronary plaque was much higher in C-type intracranial atherosclerotic stroke and the presence of coronary noncalcified plaque was independently associated with C-type intracranial atherosclerotic stroke (odds ratio, 3.38; 95% confidence interval, 1.05-10.85; P=0.041). As the number of coronary noncalcified plaques increased, positive remodeling and plaque enhancement increased in the symptomatic intracranial artery on high-resolution magnetic resonance imaging. CONCLUSIONS: Plaques within the intracranial and coronary arteries behave in similar ways. Our results suggest the need to evaluate and treat other vascular trees in patients with vulnerable plaques within a single arterial system.

Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature.

BACKGROUND: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. MATERIALS AND METHODS: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. RESULTS: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. CONCLUSIONS: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB.

Differential Vascular Pathophysiologic Types of Intracranial Atherosclerotic Stroke: A High-Resolution Wall Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stroke (ICAS) has various stroke mechanisms, including branch occlusive disease (BOD), subcortical infarcts caused by parent arterial disease occluding the perforator's orifice, and non-BOD, infarcts beyond the subcortical area caused by artery-to-artery embolism. To test whether these 2 types of ICAS had different vascular pathophysiologies, we compared the high-resolution magnetic resonance imaging characteristics between BOD and non-BOD ICAS. METHODS: Eighty patients with acute infarcts caused by ICAS of proximal middle cerebral artery or basilar artery without carotid/cardiac embolic sources or nonatherosclerotic causes were enrolled (36 BOD and 44 non-BOD patients). The steno-occlusive intracranial artery at the maximal stenosis was analyzed for vascular remodeling and wall enhancement. RESULTS: BOD had distinct radiological features in terms of vascular morphology and enhancement. BOD showed a milder stenosis than non-BOD (P<0.001). Positive remodeling was more frequently observed in non-BOD than in BOD (P=0.005). Wall area index was also lower in BOD. Plaque enhancement was observed in all but one non-BOD patient and in one fourth of BOD patients (P=0.003). Although both types showed an eccentric enhancement, this enhancement was more frequently distributed in the BOD group on the side where the perforators arose. As the number of asymptomatic intracranial stenosis increased, the degree of stenosis (rho=0.513, P=0.003) increased in the BOD group, whereas enhanced plaque area (rho=0.343, P=0.030) increased in the non-BOD group. CONCLUSIONS: Our data indicate that BOD is a common and unique form of ICAS, distinct from non-BOD. These 2 types of ICAS have different vascular pathophysiologies in terms of vascular remodeling and plaque characteristics.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

BACKGROUND AND PURPOSE: Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. METHODS: Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. RESULTS: Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). CONCLUSIONS: Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth.

A novel magnetic resonance imaging approach to collateral flow imaging in ischemic stroke.

OBJECTIVE: Dedicated magnetic resonance (MR) imaging (MRI) sequences for evaluation of collaterals can be generated using MR perfusion (MRP) source data. We compared a novel collateral flow imaging technique with digital subtraction angiography (DSA) for determining collateral circulation in acute stroke and evaluated the ability of MR-based collateral flow maps to predict outcomes after recanalization therapy. METHODS: Consecutive patients who were candidates for endovascular treatment were enrolled. A collateral flow map derived from MRP source data was generated by manual or automatic postprocessing. Collateral grading based on the collateral flow map was performed and compared with grading based on DSA. Clinical and radiological outcomes were evaluated according to MR-based collateral grading and early reperfusion (ER) status. RESULTS: There was good correlation between MRI-based and DSA-based collateral grades (weighted κ-coefficient = 0.70). Collateral status and achievement of ER were the 2 main determinants of a favorable functional outcome and neurological improvement, in addition to infarct growth. Regardless of achievement of ER, better collaterals were significantly associated with a lower modified Rankin score at day 90 (p < 0.001 for trend in both ER(-) and ER(+) ). Most symptomatic intracranial hemorrhages occurred in patients with a poor collateral grade and ER(+) , whereas no patient with excellent collaterals suffered symptomatic intracranial hemorrhage or died. INTERPRETATION: MRI techniques to assess collaterals are rapidly being developed, and may provide insight into collateral perfusion. The combination of collateral images derived from pretreatment MRP source data and reperfusion status is a robust predictor of outcomes in acute ischemic stroke.

High-resolution magnetic resonance wall imaging findings of Moyamoya disease.

BACKGROUND AND PURPOSE: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD. METHODS: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling. RESULTS: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001). CONCLUSIONS: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms.

Effects of Dietary Supplementation of Barodon, an Anionic Alkali Mineral Complex, on Growth Performance, Feed Utilization, Innate Immunity, Goblet Cell and Digestibility in Olive Flounder (Paralichthys olivaceus).

A 15-wk feeding trial was conducted to examine the supplemental effects of Barodon on growth performance, gastrointestinal histology, feed digestibility and innate immunity in olive founder. A basal commercial diet was used as a control and two other diets were prepared by spraying 0.1% or 0.2% of Barodon. Triplicate groups of fish (BW, 145 g) were fed one of the test diets to apparent satiation twice daily. At the end of the feeding trial, fish growth performance was not significantly affected by dietary treatments; however, feed utilization was significantly improved (linear and quadratic, p<0.05) by Barodon supplementation. Significantly higher (p<0.05) survival rates were obtained in fish fed Barodon containing diets. Hepatosomatic index increased significantly in Barodon treated groups. Also, the use of Barodon resulted in significant increase (linear and quadratic, p<0.05) of intestine length and number of goblet cells. Significantly higher (Quadratic, p<0.05) apparent digestibility coefficient of DM was obtained by supplementation of Barodon. Lysozyme and myeloperoxidase activities increased quadratically and linearly, respectively, in Barodon treated fish. Also, significantly higher (linear and quadratic, p<0.05) superoxide dismutase activity was found in Barodon fed fish. The findings in this study show that inclusion of Barodon in diets for olive flounder improves feed utilization and digestibility, and positively affects digestive tract histology and innate immunity.