Publications by authors named "Jiing-Feng Lirng"

128 Publications

The Impact of COVID-19 Pandemic on the Learning Outcomes of Medical Students in Taiwan: A Two-Year Prospective Cohort Study of OSCE Performance.

Int J Environ Res Public Health 2021 12 25;19(1). Epub 2021 Dec 25.

College of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan.

Background/aims: To avoid the negative impacts of the COVID-19 pandemic on clinical clerkship, supplemental teachings such as digital materials in the scenario-based distal simulations were implemented. This study utilized the OSCE (objective-structured clinical examination) to evaluate the impact of COVID-19 pandemic on the learning outcome of medical students from the regular group (class of 2020) and pandemic-impacted group (class of 2021).

Methods: All medical students serially took, firstly, the mock-OSCE, secondly, the mock-OSCE, and the national OSCE. Then, the serial OSCE scores were compared between groups.

Results: Although with similar scores in the first mock OSCE, the regular group ( = 78) had a higher average score in the national OSCE than the pandemic-impacted group ( = 80) (872.18 vs. 834.96, = 0.003). In terms of improvement, the performances of the regular group were also better than the pandemic-impacted group between the second mock OSCE and the national OSCE (79.10 vs. 38.14, = 0.014), and between the second mock OSCE and the national OSCE (125.11 vs. 77.52, = 0.003). While separating distinct genres, the regular group had more of a score increment in standardized patient-based stations between the second mock OSCE and the national OSCE (regular vs. pandemic-impacted: 57.03 vs. 18.95, = 0.003), as well as between the first mock OSCE and the national OSCE (75.97 vs. 26.36, < 0.001), but there was no significant difference among the skill-based stations. In particular, the scores of the emergency medicine associated station in the national OSCE of the pandemic-impacted group was lower.

Conclusions: Our study implies that the pandemic significantly hampered the learning outcomes of final year medical students in their clinical participation. Especially facing the COVID-19 pandemic, more supplemental teachings are needed to compensate the decreasing emergency medicine exposure.
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http://dx.doi.org/10.3390/ijerph19010208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750631PMC
December 2021

Cortical Bone Trajectory-Based Dynamic Stabilization.

World Neurosurg 2021 Dec 22. Epub 2021 Dec 22.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Background: Cortical bone trajectory (CBT) screws have demonstrated similar biomechanical strength and fusion rates as conventional pedicle screws for short-segment lumbar fusion. However, very few studies have verified the viability of CBT screws in dynamic stabilization. In the present study, we compared the clinical outcomes of CBT-based Dynesys dynamic stabilization (CBT-DDS) with standard minimally invasive transforaminal lumbar interbody fusion (MI-TLIF).

Methods: Consecutive patients who had undergone CBT-DDS or MI-TLIF at L4-L5 or L3-L5 were retrospectively reviewed. All the radiological and clinical outcomes were compared between the 2 groups. The patient-reported outcomes included the visual analog scale scores for back and leg pain, Japanese Orthopaedic Association scores, and Oswestry disability index. The pre- and postoperative radiological evaluations were also reviewed.

Results: A total of 60 patients (20 patients in the CBT-DDS and 40 in the MI-TLIF groups) were analyzed. The MI-TLIF group had required a longer operation time (P = 0.010) than the CBT-DDS group but had had a similar estimated blood loss (P = 0.484). The perioperative complications, including screw loosening, wound infection, and radiculopathy, were similar in both groups (P > 0.05 for all). The degree of decreased range of motion after surgery was similar between the 2 groups (P = 0.781), and no pseudarthrosis developed in the MI-TLIF group.

Conclusions: Because the clinical and radiological outcomes of CBT-DDS were similar to those of MI-TLIF in patients with L4-L5 or L3-L5 spondylosis and spondylolisthesis, CBT-DDS appears to be a viable and effective alternative to MI-TLIF, with a shorter operation time and similarly limited segmental motility.
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http://dx.doi.org/10.1016/j.wneu.2021.12.061DOI Listing
December 2021

Simple parameters of synthetic MRI for assessment of bone density in patients with spinal degenerative disease.

J Neurosurg Spine 2021 Oct 15:1-8. Epub 2021 Oct 15.

1Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Objective: Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements.

Methods: This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine.

Results: There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = -0.565 and -0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = -0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ -1.0) and osteoporosis (T-score ≤ -2.5) with PD (both p < 0.001).

Conclusions: PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.
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http://dx.doi.org/10.3171/2021.6.SPINE21666DOI Listing
October 2021

The time sequence of brain MRI findings in spontaneous intracranial hypotension.

Cephalalgia 2022 Jan 27;42(1):12-19. Epub 2021 Sep 27.

College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Objectives: To investigate the time sequence of brain magnetic resonance imaging findings of spontaneous intracranial hypotension.

Methods: We retrospectively reviewed the medical records and brain magnetic resonance imaging findings of consecutive patients with spontaneous intracranial hypotension hospitalized between January 2007 and December 2017. Patients were divided into quartiles based on intervals between initial spontaneous intracranial hypotension symptom onset and brain magnetic resonance imaging scan. Six categorical and five continuous brain magnetic resonance imaging findings were assessed, including venous distension sign, enlarged pituitary gland, diffuse pachymeningeal enhancement, mid-brain pons deformity, subdural fluid collection, flattening of pons, midbrain-pons angle, descent of cerebral aqueduct, mamillopontine distance, distance of suprasellar cistern, and distance of prepontine cistern. In addition, we also calculated the neuroimaging scores with a score ≥5 classified as 'high probability of spontaneous intracranial hypotension' and a score ≥3 as 'intermediate-to-high probability.' Then, we analyzed the linkage between the onset-neuroimaging interval and brain magnetic resonance imaging findings, as well as different neuroimaging scores.

Results: A total of 173 patients (57 males and 116 females) were included in the analysis, and the range of onset-neuroimaging interval was 1 to 89 days (median [interquartile range]  =  17 [7 to 30 days]). We divided the patients into quartiles based on their onset-neuroimaging interval (the first quartile: 0-6 days; the second quartile: 7-16 days; the third quartile: 17-29 days; the fourth quartile: ≥30 days). Among brain magnetic resonance imaging findings, the incidence of venous distension sign was high (>75%), with no difference among quartiles (p = 0.876). The incidence of diffuse pachymeningeal enhancement (p = 0.001), severe midbrain-pons deformity (p = 0.001), and subdural fluid collection (<0.001) followed a significant stepwise increase from the first quartile to fourth quartile. Patients with shorter onset-neuroimaging intervals were less likely to have neuroimaging scores ≥5 (<17 vs. ≥17 days: 72.9% vs. 86.4%; odds ratio = 2.3 [95% CI 1.1-5.1], p = 0.028), but not neuroimaging scores ≥3 (<17 vs. ≥17 days: 92.9% vs. 92.0%, p = 0.824).

Conclusions: The emergence of brain magnetic resonance imaging findings of spontaneous intracranial hypotension depended on disease duration and appeared sequentially. When using brain magnetic resonance imaging findings or neuroimaging scores for diagnostic purposes, the onset-neuroimaging interval should be considered.
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http://dx.doi.org/10.1177/03331024211044424DOI Listing
January 2022

Blood-Brain Barrier Permeability in Patients With Reversible Cerebral Vasoconstriction Syndrome Assessed With Dynamic Contrast-Enhanced MRI.

Neurology 2021 11 9;97(18):e1847-e1859. Epub 2021 Sep 9.

From the Department of Radiology (C.-H.W., J.-F.L., H.-M.W., C.-J.L., K.L.), Department of Neurology, Neurological Institute (Y.-H.L., Y.-F.W., J.-L.F., S.-J.W., S.-P.C.), and Division of Translational Research, Department of Medical Research (S.-P.C.), Taipei Veterans General Hospital; and Institute of Clinical Medicine (C.-H.W., S.-P.C.), School of Medicine (C.-H.W., J.-F.L., H.-M.W., Y.-H.L., Y.-F.W., J.-L.F., C.-J.L., K.L., S.-J.W., S.-P.C.), and Brain Research Center (Y.-F.W., J.-L.F., S.-J.W., S.-P.C.), National Yang Ming Chiao Tung University, Taipei, Taiwan.

Background And Objectives: Blood-brain barrier (BBB) disruption has been proposed to be important in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS), but not all patients present an identifiable macroscopic BBB disruption; that is, visible contrast leakage on contrast-enhanced T2 fluid-attenuated inversion recovery imaging. This study aimed to evaluate microscopic BBB permeability and its dynamic change in patients with RCVS.

Methods: This prospective cohort implemented 3T dynamic contrast-enhanced MRI. We measured microscopic BBB permeability by determining the whole-brain and white matter hyperintensity (WMH) K values and evaluated the correlation of whole-brain K permeability with clinical and vascular measures in transcranial color-coded sonography.

Results: In total, 176 patients (363 scans) were analyzed and separated into acute (≦30 days) and remission (≧90 days) groups based on the onset-to-examination time. Whole-brain K values were similar between patients with and without macroscopic BBB disruption in either acute or remission stage. The whole-brain K was significantly decreased ( < 0.001) from acute to remission stages. The WMH K was significantly higher than mirror references and decreased from acute to remission stages ( < 0.001). Whole-brain K correlated with mean pulsatility index ( = 0.5, = 0.029), mean resistance index ( = 0.662, = 0.002), and distal-to-proximal ratio of resistance index ( = 0.801, < 0.001) of M1 segment of middle cerebral arteries at around 10-15 days after onset. The time-trend curve of whole-brain K depicted dynamic changes during disease course, similar to temporal trends of vasoconstrictions and WMH.

Discussion: Patients with RCVS presented increased microscopic brain permeability during acute stage, even without discernible macroscopic BBB disruption. The dynamic changes in BBB permeability may be related to impaired cerebral microvascular compliance and WMH formation.
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http://dx.doi.org/10.1212/WNL.0000000000012776DOI Listing
November 2021

Correlation of bone density to screw loosening in dynamic stabilization: an analysis of 176 patients.

Sci Rep 2021 09 1;11(1):17519. Epub 2021 Sep 1.

Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Beitou District, Taipei, 112, Taiwan, ROC.

Although osteoporosis has negative impacts on lumbar fusion, its effects on screw loosening in dynamic stabilization remain elusive. We aimed to correlate bone mineral density (BMD) with screw loosening in Dynesys dynamic stabilization (DDS). Consecutive patients who underwent 2- or 3-level DDS for spondylosis, recurrent disc herniations, or low-grade spondylolisthesis at L3-5 were retrospectively reviewed. BMD was assessed by the Hounsfield Unit (HU) in vertebral bodies (VB) and pedicles with and without cortical bone (CB) on pre-operative computed tomography (CT). Screw loosening was assessed by radiographs and confirmed by CT. HU values were compared between the loosened and intact screws. 176 patients and 918 screws were analyzed with 78 loosened screws found in 36 patients (mean follow-up: 43.4 months). The HU values of VB were similar in loosened and intact screws (p = 0.14). The HU values of pedicles were insignificantly less in loosened than intact screws (including CB: 286.70 ± 118.97 vs. 297.31 ± 110.99, p = 0.45; excluding CB: 238.48 ± 114.90 vs. 240.51 ± 108.91, p = 0.88). All patients had clinical improvements. In conclusion, the HU values, as a surrogate for BMD, were unrelated to screw loosening in DDS. Therefore, patients with compromised BMD might be potential candidates for dynamic stabilization rather than fusion.
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http://dx.doi.org/10.1038/s41598-021-95232-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410763PMC
September 2021

Sub-regional hippocampal volumes in first-episode drug-naïve major depression disorder.

Neurosci Lett 2021 10 18;763:136178. Epub 2021 Aug 18.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112201, Taiwan; Center for Quality Management, Taipei Veterans General Hospital, Taipei 112201, Taiwan. Electronic address:

Hippocampal volume reduction was reported to underlie depressive symptomatology, however, the evidence to date remains inconsistent. For the complex intrinsic organization of hippocampus, the hippocampal volumes can be further divided into subfields or axial parts. The current study aimed to explore the alterations of hippocampal sub-regional volumes in first episode drug-naïve major depressive disorder (MDD) by two segmentation methods. Thirty-five first-episode drug-naïve MDD and 35 age- and gender-matched healthy controls (HC) were recruited. Volumes of three sub-regions of hippocampus along the longitudinal axis (head, body and tail) were analyzed manually and eight transverse subfields were automatically determined using FreeSurfer. An asymmetric index (AI) of volumes was defined as (∣Left - Right∣/∣Left + Right∣) * 100. There were significant reductions in the volumes of bilateral hippocampal head in MDD compared to HC. The volumes of eight subfields were not different between groups. MDD patients had higher AI values in the subfield of cornu ammonis 4/dentate gyrus than HC. The change in hippocampal sub-regional volumes might be an imaging biomarker in the first-episode, drug-naïve patients with MDD. Current findings may contribute to developing new diagnostic and therapeutic strategies for major depression.
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http://dx.doi.org/10.1016/j.neulet.2021.136178DOI Listing
October 2021

Diagnosis and classification of headache associated with sexual activity using a composite algorithm: A cohort study.

Cephalalgia 2021 12 18;41(14):1447-1457. Epub 2021 Jul 18.

Department of Neurology, 46615Taipei Veterans General Hospital, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: To differentiate primary headache associated with sexual activity from other devastating secondary causes.

Methods: In this prospective cohort, we recruited consecutive patients with at least 2 attacks of headache associated with sexual activity from the headache clinics or emergency department of a national medical center from 2005 to 2020. Detailed interview, neurological examination, and serial thorough neuroimaging including brain magnetic resonance imaging and magnetic resonance angiography scans were performed on registration and during follow-ups. Patients were categorized into four groups, i.e. primary headache associated with sexual activity, reversible cerebral vasoconstriction syndrome, probable reversible cerebral vasoconstriction syndrome, and other secondary headache associated with sexual activity through a composite clinic-radiological diagnostic algorithm. We compared the clinical profiles among these groups, including sex, age of onset, duration, quality, and clinical course ("chronic" indicates disease course ≥ 1 year). In addition, we also calculated the score of the reversible cerebral vasoconstriction syndrome, a scale developed to differentiate reversible cerebral vasoconstriction syndrome from other intracranial vascular disorders.

Results: Overall, 245 patients with headache associated with sexual activity were enrolled. Our clinic-radiologic composite algorithm diagnosed and classified all patients into four groups, including 38 (15.5%) with primary headache associated with sexual activity, 174 (71.0%) with reversible cerebral vasoconstriction syndrome, 26 (10.6%) with probable reversible cerebral vasoconstriction syndrome, and 7 (2.9%) with other secondary causes (aneurysmal subarachnoid hemorrhage (n = 4), right internal carotid artery dissection (n = 1), Moyamoya disease (n = 1), and meningioma with hemorrhage (n = 1)). These four groups shared similar clinical profiles, except 26% of the patients with primary headache associated with sexual activity had a 3 times greater chance of running a chronic course (≥ 1 year) than patients with reversible cerebral vasoconstriction syndrome. Of note, the reversible cerebral vasoconstriction syndrome score could not differentiate reversible cerebral vasoconstriction syndrome from other groups.

Conclusion: Our composite clinic-radiological diagnostic algorithm successfully classified repeated headaches associated with sexual activity, which were predominantly secondary and related to vascular disorders, and predicted the prognosis. Primary headache associated with sexual activity and reversible cerebral vasoconstriction syndrome presented with repeated attacks of headache associated with sexual activity may be of the same disease spectrum.
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http://dx.doi.org/10.1177/03331024211028965DOI Listing
December 2021

Post-reversible cerebral vasoconstriction syndrome headache.

J Headache Pain 2021 Mar 25;22(1):14. Epub 2021 Mar 25.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Chronic headache may persist after the remission of reversible cerebral vasoconstriction syndrome (RCVS) in some patients. We aimed to investigate the prevalence, characteristics, risk factors, and the impact of post-RCVS headache.

Methods: We prospectively recruited patients with RCVS and collected their baseline demographics, including psychological distress measured by Hospital Anxiety and Depression scale. We evaluated whether the patients developed post-RCVS headache 3 months after RCVS onset. The manifestations of post-RCVS headache and headache-related disability measured by Migraine Disability Assessment (MIDAS) scores were recorded.

Results: From 2017 to 2019, 134 patients with RCVS were recruited, of whom, 123 finished follow-up interviews (response rate 91.8%). Sixty (48.8%) patients had post-RCVS headache. Migrainous features were common in post-RCVS headache. Post-RCVS headache caused moderate-to-severe headache-related disability (MIDAS score > 10) in seven (11.7%) patients. Higher anxiety level (odds ratio 1.21, p = 0.009) and a history of migraine (odds ratio 2.59, p = 0.049) are associated with post-RCVS headache. Survival analysis estimated that 50% post-RCVS headache would recover in 389 days (95% confidence interval: 198.5-579) after disease onset.

Conclusions: Post-RCVS headache is common, affecting half of patients and being disabling in one-tenth. Higher anxiety level and migraine history are risk factors. Half of the patients with post-RCVS headache would recover in about a year.
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http://dx.doi.org/10.1186/s10194-021-01223-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992969PMC
March 2021

Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome.

Ann Neurol 2021 03 30;89(3):459-473. Epub 2020 Dec 30.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).

Methods: We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis.

Results: We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-β signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model.

Interpretation: We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.
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http://dx.doi.org/10.1002/ana.25965DOI Listing
March 2021

Interaction of dopamine transporter and metabolite ratios underpinning the cognitive dysfunction in patients with carbon monoxide poisoning: A combined SPECT and MRS study.

Neurotoxicology 2021 01 7;82:26-34. Epub 2020 Nov 7.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Center for Quality Management, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with Tc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.
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http://dx.doi.org/10.1016/j.neuro.2020.11.002DOI Listing
January 2021

Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood-Brain Barrier Leakage.

Ann Neurol 2021 01 23;89(1):111-124. Epub 2020 Oct 23.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Objective: To evaluate human glymphatics and meningeal lymphatics noninvasively.

Methods: This prospective study implemented 3-dimensional (3D) isotropic contrast-enhanced T2 fluid-attenuated inversion recovery (CE-T2-FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood-brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol/kg [0.2ml/kg]) was administered intravenously in all study subjects.

Results: In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para-arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase- or condition-specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54 minutes and was completely cleared within 18 hours.

Interpretation: This large-scale in vivo study successfully demonstrated the putative human para-arterial glymphatic transports and meningeal lymphatics by clear depiction of para-arterial, parasinus, and paravenous meningeal contrast enrichment using high-resolution 3D isotropic CE-T2-FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111-124.
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http://dx.doi.org/10.1002/ana.25928DOI Listing
January 2021

Brain volume changes in spontaneous intracranial hypotension: Revisiting the Monro-Kellie doctrine.

Cephalalgia 2021 01 26;41(1):58-68. Epub 2020 Aug 26.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objectives: In the application of the Monro-Kellie doctrine in spontaneous intracranial hypotension, the brain tissue volume is generally considered as a fixed constant. Traditionally, cerebral venous dilation is thought to compensate for decreased cerebrospinal fluid. However, whether brain tissue volume is invariable has not yet been explored. The objective of this study is to evaluate whether brain tissue volume is fixed or variable in spontaneous intracranial hypotension patients using automatic quantitative methods.

Methods: This retrospective and longitudinal study analyzed spontaneous intracranial hypotension patients between 1 January 2007 and 31 July 2015. Voxel-based morphometry was used to examine brain volume changes during and after the resolution of spontaneous intracranial hypotension. Brain structure volume was analyzed using Statistical Parametric Mapping version 12 and FMRIB Software Library v6.0. Post-treatment neuroimages were used as surrogate baseline measures.

Results: Forty-four patients with spontaneous intracranial hypotension were analyzed (mean [standard deviation] age, 37.8 [8.5] years; 32 female and 12 male). The whole brain tissue volume was decreased during spontaneous intracranial hypotension compared to follow-up (1180.3 [103.5] mL vs. 1190.4 [93.1] mL, difference: -10.1 mL [95% confidence interval: -18.4 to -1.8 mL],  = 0.019). In addition, ventricular cerebrospinal fluid volume was decreased during spontaneous intracranial hypotension compared to follow-up (15.8 [6.1] mL vs. 18.9 [6.9] mL, difference: -3.2 mL [95% confidence interval: -4.5 to -1.8 mL],  < 0.001). Longer anterior epidural cerebrospinal fluid collections, as measured by number of vertebral segments, were associated with greater reduction of ventricular cerebrospinal fluid volume (Pearson's r = -0.32,  = 0.036).

Conclusion: The current study found the brain tissue volume and ventricular cerebrospinal fluid are decreased in spontaneous intracranial hypotension patients. The change in ventricular cerebrospinal fluid volume, but not brain tissue volume change, was associated with the severity of spinal cerebrospinal fluid leakage. These results challenge the assumption that brain tissue volume is a fixed constant.
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http://dx.doi.org/10.1177/0333102420950385DOI Listing
January 2021

Long-term imaging follow-up to evaluate restenosis in patients with carotid stenosis after angioplasty and stenting.

J Chin Med Assoc 2021 Jan;84(1):87-94

Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Stent patency after carotid angioplasty and stenting (CAS) correlates not only with stroke prevention but also with improvements in cognition and quality of life by positively influencing cerebral perfusion. The long-term outcomes of CAS after more than 5 years have still not been well described. This retrospective study was designed to evaluate the stent patency and significant restenosis (SR) after CAS with more than 5 years of follow-up.

Methods: Between 2006 and 2012, 118 patients with carotid stenosis who underwent 131 CAS procedures with regular annual imaging follow-up for more than 5 years were enrolled. We evaluated their demographic characteristics and the risk factors related to stent restenosis. Patients with SR (restenosis ≥ 50%) were compared with those with no significant restenosis (NSR, patency or restenosis < 50%) to identify the restenosis predictors and restenosis-free survival.

Results: Of the 131 CAS procedures, 16.0% (21/131) had SR. A history of head and neck radiotherapy (HNRT) was a predictor for SR (HR, 6.352; 95% CI, 2.504-16.112; p < 0.001) and was associated with shorter restenosis-free survival (log-rank test p value < 0.001, median time of restenosis-free survival was 38 months). Left-sided stenting was an associated factor for SR (HR, 3.007; 95% CI, 1.068-8.467; p = 0.037) with a trend of less restenosis-free survival (log-rank test p value 0.067).

Conclusion: Both HNRT and left-sided carotid stenosis were predictors of SR after CAS in more than 5 years of long-term follow-up. Restenosis-free survival was significantly shorter in patients with prior HNRT than in patients without previous irradiation treatment. We suggest close follow-up and aggressive medical treatment for patients with prior HNRT and left-sided carotid stenosis undergoing CAS.
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http://dx.doi.org/10.1097/JCMA.0000000000000405DOI Listing
January 2021

Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit.

J Clin Med 2020 Jul 29;9(8). Epub 2020 Jul 29.

Department of Radiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)-characterized as tumors mimicking malignant orbital lymphoma (OL)-responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL.

Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios.

Results: Significantly related to IgG4-ROD (all < 0.05) were the presence of lesions with regular borders, presence of multiple lesions-involving both lacrimal glands on CT scans-higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674-1.000, = 0.005] vs. 0.766 [95% CI: 0.615-0.917, = 0.002]), higher sensitivity (0.889 [95% CI: 0.518-0.997] vs. 0.75 [95% CI: 0.509-0.913]), higher specificity (0.813 [95% CI: 0.544-0.960] vs. 0.778 [95% CI: 0.578-0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5).

Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.
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http://dx.doi.org/10.3390/jcm9082425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463766PMC
July 2020

The Effect of T1-Slope in Spinal Parameters After Cervical Disc Arthroplasty.

Neurosurgery 2020 11;87(6):1231-1239

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Although patients with cervical kyphosis are not ideal candidates for cervical disc arthroplasty (CDA), there is a paucity of data on patients with a straight or slightly lordotic neck.

Objective: To correlate cervical lordosis, T1-slope, and clinical outcomes of CDA.

Methods: The study retrospectively analyzed 95 patients who underwent 1-level CDA and had 2-yr follow-up. They were divided into a high T1-slope (≥28°) group (HTSG, n = 45) and a low T1-slope (<28°) group (LTSG, n = 50). Cervical spinal alignment parameters, including T1-slope, cervical lordosis (C2-7 Cobb angle), and segmental mobility (range of motion [ROM]) at the indexed level, were compared. The clinical outcomes were also assessed.

Results: The mean T1-slope was 28.1 ± 7.0°. After CDA, the pre- and postoperative segmental motility remained similar and cervical lordosis was preserved. All the clinical outcomes improved after CDA. The HTSG were similar to the LTSG in age, sex, segmental mobility, and clinical outcomes. However, the HTSG had higher cervical lordosis than the LTSG. Furthermore, the LTSG had increased cervical lordosis (ΔC2-7 Cobb angle), whereas the HTSG had decreased lordosis after CDA. Patients of the LTSG, who had more improvement in cervical lordosis, had a trend toward increasing segmental mobility at the index level (ΔROM) than the HTSG.

Conclusion: In this series, T1-slope correlated well with global cervical lordosis but did not affect the segmental mobility. After CDA, the changes in cervical lordosis correlated with changes in segmental mobility. Therefore, segmental lordosis should be cautiously preserved during CDA as it could determine the mobility of the disc.
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http://dx.doi.org/10.1093/neuros/nyaa271DOI Listing
November 2020

Effects of smoking on pedicle screw-based dynamic stabilization: radiological and clinical evaluations of screw loosening in 306 patients.

J Neurosurg Spine 2020 May 1:1-8. Epub 2020 May 1.

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: Cigarette smoking has been known to increase the risk of pseudarthrosis in spinal fusion. However, there is a paucity of data on the effects of smoking in dynamic stabilization following lumbar spine surgery. This study aimed to investigate the clinical outcomes and the incidence of screw loosening among patients who smoked.

Methods: Consecutive patients who had lumbar spondylosis, recurrent disc herniations, or low-grade spondylolisthesis that was treated with 1- or 2-level surgical decompression and pedicle screw-based Dynesys dynamic stabilization (DDS) were retrospectively reviewed. Patients who did not complete the minimum 2 years of radiological and clinical evaluations were excluded. All screw loosening was determined by both radiographs and CT scans. Patient-reported outcomes, including visual analog scale (VAS) scores of back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI), were analyzed. Patients were grouped by smoking versus nonsmoking, and loosening versus intact screws, respectively. All radiological and clinical outcomes were compared between the groups.

Results: A total of 306 patients (140 women), with a mean age of 60.2 ± 12.5 years, were analyzed during an average follow-up of 44 months. There were 34 smokers (9 women) and 272 nonsmokers (131 women, 48.2% more than the 26.5% of smokers, p = 0.017). Postoperatively, all the clinical outcomes improved (e.g., VAS back and leg pain, JOA scores, and ODI, all p < 0.001). The overall rate of screw loosening was 23.2% (71 patients), and patients who had loosened screws were older (61.7 ± 9.6 years vs 59.8 ± 13.2 years, p = 0.003) and had higher rates of diabetes mellitus (33.8% vs 21.7%, p = 0.038) than those who had intact DDS screws. Although the patients who smoked had similar clinical improvement (even better VAS scores in their legs, p = 0.038) and a nonsignificantly lower rate of screw loosening (17.7% and 23.9%, p = 0.416), the chances of secondary surgery for adjacent segment disease (ASD) were higher than for the nonsmokers (11.8% vs 1.5%, p < 0.001).

Conclusions: Smoking had no adverse effects on the improvements of clinical outcomes in the pedicle screw-based DDS surgery. For smokers, the rate of screw loosening trended lower (without significance), but the chances of secondary surgery for ASD were higher than for the nonsmoking patients. However, the optimal surgical strategy to stabilize the lumbar spine of smoking patients requires future investigation.
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http://dx.doi.org/10.3171/2020.2.SPINE191380DOI Listing
May 2020

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

Stroke 2020 05 17;51(5):1451-1457. Epub 2020 Apr 17.

From the Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (S.C., M.J.L., C.-S.C.).

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 (β, 3.35 [95% CI, 0.07-6.64]; =0.046) and blood pressure surge (β, 3.84 [95% CI, 1.75-5.92]; <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 ( 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.
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http://dx.doi.org/10.1161/STROKEAHA.119.028656DOI Listing
May 2020

Influence of Vertebrobasilar Stenotic Lesion Rigidity on the Outcome of Angioplasty and Stenting.

Sci Rep 2020 03 3;10(1):3923. Epub 2020 Mar 3.

Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.

Stenotic lesion rigidity (SLR) has an unclear influence on the outcome of percutaneous transluminal angioplasty and stenting (PTAS) for intracranial arterial stenosis. This study evaluated the outcome of PTAS and the relationship of vertebrobasilar SLR to features on vessel wall MRI (VW-MRI) for identifying pathologies of vertebrobasilar stenosis (VBS) and evaluating PTAS outcome. We retrospectively evaluated the results of PTAS in 31 patients with severe VBS. Stenotic lesions were classified as soft (based on predilatation pressure [PP] ≦ 4 atm) in 15 patients or hard (PP >4 atm) in 16 patients. We examined the relationship of SLR to clinical and MR findings. Patients with hard vs soft lesions had atherosclerosis (8/16 [50.0%] vs 2/15 [13.3%]), dissection (0/16 [0.0%] vs 12/15 [80.0%]), and dissection in atherosclerosis (8/16 [50.0%] vs 1/15 [6.7%], P < 0.0001); high intensity signal on the T1WI of VW-MRI (5/16 [31.3%] vs 14/15 [93.3%]) and iso- to low intensity signal (11/16 [68.7%] vs 1/15 [6.7], P = 0.001), and significant in-stent restenosis (>50%) in 5/15 (33.3%) vs 0/15 (0.0%) (P = 0.0421) in the 30 patients who successfully completed PTAS. Vertebrobasilar SLR correlated well with lesion etiology, findings on VW-MRI, and PTAS outcome. Patients with hard stenotic lesions need close follow-up after PTAS.
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http://dx.doi.org/10.1038/s41598-020-60906-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054424PMC
March 2020

Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

Radiology 2020 04 11;295(1):171-180. Epub 2020 Feb 11.

From the Division of Neuroradiology, Park 367B, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287 (M.P., M.M., A.B., K.L.C., G.O., N.A.J.P., M.G.S., R.A.E.E., P.B.B.); F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD (M.P., M.M., A.B., K.L.C., G.O., N.A.J.P., M.G.S., R.A.E.E., P.B.B.); Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH (P.K.B.); Department of Radiology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH (P.K.B.); Department of Radiology, Haukeland University Hospital, Bergen, Norway (M.K.B.); Spinoza Centre for Neuroimaging, Amsterdam, the Netherlands (P.F.B., D.S.); Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH (K.M.C.); Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD (K.L.C.); Department of Radiology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan (D.Y.T.C.); Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (D.Y.T.C.); Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway (A.R.C., L.E.); NOreMENT-Norwegian Center for Mental Disorders Research, University of Bergen, Bergen, Norway (A.R.C., L.E.); Movement Control & Neuroplasticity Research Group, Department of Movement Sciences, Group of Biomedical Sciences, KU Leuven, Leuven, Belgium (K.C., C.M., S.P.S.); REVAL Rehabilitation Research Center, Hasselt University, Diepenbeek, Belgium (K.C.); Department of Radiology, Medical Physics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (M.D., T.L.); Brain and Consciousness Research Centre, Taipei Medical University, Taipei, Taiwan (N.W.D.); School of Health Sciences, Purdue University, West Lafayette, IN (U.D., D.A.E., R.M.); Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN (U.D., D.A.E.); Department of Neuroimaging, Central Institute of Mental Health, Mannheim, Germany (G.E., M.S.); Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway (A.R.C., L.E.); Department of Clinical and Health Psychology, University of Florida, Gainesville, FL (M.A.F., E.C.P., A.J.W.); Center for Cognitive Aging and Memory, McKnight Brain Institute, University of Florida, Gainesville, FL (M.A.F., E.C.P., A.J.W.); Shandong Medical Imaging Research Institute, Shandong University, Jinan, China (F.G., G.W.); Department of Human Physiology, University of Oregon, Eugene, OR (I.G.); Department of Radiology, University of Calgary, Calgary, Canada (A.D.H.); Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (N. He, Y.L., H.X., F.Y.); Department of Neurology, BG University Hospital Bergmannsheil, Bochum, Germany (S.H., M.T.); Academic Unit of Radiology, University of Sheffield, Sheffield, England (N. Hoggard, I.D.W.); Department of Radiology, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan (T.W.H., J.K.L., J.F.L.); Department of Radiology, Maastricht University Medical Center, Maastricht, the Netherlands (J.F.A.J.); Department of Psychiatry, Columbia University, New York, NY (A.K.. M.M.O.); New York State Psychiatric Institute, New York, NY (A.K., F.L.); GE Healthcare, Calgary, Canada (R.M.L.); GE Healthcare, Taipei, Taiwan (C.Y.E.L.); Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL (J.R.L.); National High Magnetic Field Laboratory, Gainesville, FL (J.R.L.); Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN (R.M.); Department of Psychology, University of Washington, Seattle, WA (S.O.M., M.P.S.); Center for Mind and Brain, University of California, Davis, Davis, CA (S.N.); GE Healthcare, Berlin, Germany (R.N.); Department of Electrical and Computer Engineering, McMaster University, Hamilton, Canada (M.D.N.); Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC (J.J.P.); Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA (T.P.L.R.); Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada (N. Sailasuta, P.T.); Department of Psychiatry, University of Toronto, Toronto, Canada (N. Sailasuta); Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN (M.P.S.); School of Biomedical Engineering, McMaster University, Hamilton, Canada (N. Simard); Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium (S.P.S.); Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany (H.J.W., H.J.Z.); Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (C.Z.); Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.Y.); and Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany (H.J.Z.).

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. values were derived through parametric bootstrapping of the linear mixed-effects models (denoted ). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of -acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol ( > .90), -acetylaspartate and -acetylaspartylglutamate ( = .13), or glutamate and glutamine ( = .11). Among the smaller resonances, no vendor effects were found for ascorbate ( = .08), aspartate ( > .90), glutathione ( > .90), or lactate ( = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020191037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104702PMC
April 2020

Natural History of Acromegaly: Incidences, Re-operations, Cancers, and Mortality Rates in a National Cohort.

Neuroendocrinology 2020 11;110(11-12):977-987. Epub 2019 Dec 11.

School of Medicine, National Yang-Ming University, Taipei, Taiwan,

Background: Acromegaly is so rare that its natural history, including incidence, risk of cancers, and mortality rates, remains elusive. This natural study utilized a nationwide database to provide a better understanding of acromegaly's disease course.

Methods: A cohort of 1,195 acromegaly patients were identified and followed-up from 1997 to 2013. Incidence, operation, and re-operation rates were calculated. Excessive mortality and cancer risk related to acromegaly were estimated by standardized mortality ratio (SMR) and standardized incidence ratio (SIR).

Results: The incidence was 2.78 per million-person-years, with little gender predominance (female vs. male, 49.5 vs. 50.5%, respectively). There was female predominance only among 50 and 60 year-olds (incidence rate ratio: 1.37 and 1.43, p < 0.001 and p = 0.002). Among them, 673 (56.3%) had hypophysectomy surgery, and the young-onset (<40 years) patients had more re-operations (15.5%, p = 0.01). The overall mortality rate was 22.3 per 1,000 person-years, with a median survival of 4.67 years (with no gender differences, p = 0.38). The overall SMR of acromegaly patients was 1.41, and the onset-age-specific SMRs of the early- and middle-onset patients were higher than for those with late-onset. There were 87 newly diagnosed cancers in the cohort, with an incidence rate of 10.6 per 1,000 person-years (median 5.4 years). The overall SIR of cancers was 1.91, and there were no differences among gender, onset-age, and disease duration (all SIR >1, approximately 2).

Conclusion: Acromegaly is associated with an excessive risk of mortality and two-fold higher risk of cancers. Patients with acromegaly should be managed appropriately after the diagnosis.
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http://dx.doi.org/10.1159/000505332DOI Listing
August 2021

Radiological and clinical outcomes of 3-level cervical disc arthroplasty.

J Neurosurg Spine 2019 Nov;32(2):174-181

3Department of Biomedical Imaging and Radiological Sciences, and.

Objective: One- and two-level cervical disc arthroplasty (CDA) has been compared to anterior cervical discectomy and fusion (ACDF) in several large-scale, prospective, randomized trials that have demonstrated similar clinical outcomes. However, whether these results would be similar when treating 3-level disc herniation and/or spondylosis has remained unanswered. This study aimed to investigate the differences between 3-level CDA and ACDF.

Methods: A series of 50 patients who underwent 3-level CDA at C3-7 was retrospectively reviewed and compared with another series of 50 patients (age- and sex-matched controls) who underwent ACDF at C3-7. Clinical outcomes were measured using the visual analog scale (VAS) for neck and arm pain, the modified Japanese Orthopaedic Association (mJOA) scale, and the Neck Disability Index (NDI). Radiological outcomes included range of motion (ROM) at the index levels. Every patient was evaluated by CT for the presence of fusion in the ACDF group. Also, complication profiles were investigated.

Results: The demographics and levels of distribution in both groups were very similar. During the follow-up period of 24 months, clinical outcomes improved (overall and respectively in each group) for both the CDA and ACDF patients when compared with the patients' preoperative condition. There were essentially few differences between the two groups in terms of neck and arm pain VAS scores, mJOA scores, and NDI scores preoperatively and at 3, 6, 12, and 24 months postoperatively. After the 3-level surgery, the CDA group had an increased mean ROM of approximately 3.4°, at 25.2° ± 8.84°, compared to their preoperative ROM (21.8° ± 7.20°) (p = 0.001), whereas the ACDF group had little mobility (22.8° ± 5.90° before and 1.0° ± 1.28° after surgery; p < 0.001). The mean operative time, estimated blood loss, and complication profiles were similar for both groups.

Conclusions: In this selectively matched retrospective study, clinical outcomes after 3-level CDA and ACDF were similar during the 2-year follow-up period. CDA not only successfully preserved but slightly increased the mobility at the 3 index levels. However, the safety and efficacy of 3-level CDA requires more long-term data for validatation.
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http://dx.doi.org/10.3171/2019.8.SPINE19545DOI Listing
November 2019

A pilot study of integrating standardized patients in problem-based learning tutorial in Taiwan.

J Chin Med Assoc 2019 Jun;82(6):464-468

Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Problem-based learning (PBL) has been widely adopted in medical education; however, its application has been questioned due to the lack of interaction with a real patient. Standardized patients (SPs) might solve this problem. Herein, we tested the impact of integrating SPs in a PBL tutorial.

Methods: In 2017, a total of 313 students, 66 facilitators, and 36 SPs were enrolled at National Yang-Ming University, Taiwan. The SPs presented the symptoms/signs of the cases then the students interviewed them to obtain the detail history. All students, facilitators, and SPs were invited to complete the questionnaires before and after this program.

Results: Most SPs considered that both the second-year dental medical student and third-year medical students participated actively and were competent enough but students and facilitators considered that the fourth-year medical students might be more prepared. Overall, the students thought highly of the interactions with the SPs. Only about one-fifth felt that this design caused unnecessary pressure among the students and facilitators. They agreed that this program significantly inspired the student's learning motivation (pre- vs post-course: 4.1 ± 0.7 vs 4.3 ± 0.7, p < 0.001), increased their confidence level in interviewing patients (4.0 ± 0.8 vs 4.2 ± 0.7, p < 0.001), and encouraging critical thinking (4.0 ± 0.7 vs 4.2 ± 0.7, p < 0.001).

Conclusion: The SPs, facilitators, and students had different viewpoints with regards to integrating SPs in the PBL tutorial. However, a majority agreed that this design enhanced the motivation of students and supported such an application in PBL tutorials.
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http://dx.doi.org/10.1097/JCMA.0000000000000109DOI Listing
June 2019

Long Term Outcomes and Effects of Surgery on Degenerative Spinal Deformity: A 14-Year National Cohort Study.

J Clin Med 2019 Apr 10;8(4). Epub 2019 Apr 10.

School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.

Degenerative spinal deformity (DSD) has become a prevalent cause of disability and pain among the aging population worldwide. Though surgery has emerged as a promising option for DSD, the natural course, outcomes, and effects of surgery on DSD have remained elusive. This cohort study used a national database to comprehensively follow up patients of DSD for all-cause mortality, respiratory problems, and hip fracture-related hospitalizations. All patients were grouped into an operation or a non-operation group for comparison. An adjustment of demographics, comorbidities, and propensity-score matching was conducted to ameliorate confounders. A Cox regression hazard ratio (HR) model and Kaplan-Meier analysis were also applied. The study comprised 21,810 DSD patients, including 12,544 of the operation group and 9266 of the non-operation group. During the 14 years (total 109,591.2 person-years) of follow-up, the operation group had lower mortality (crude hazard ratio = 0.40), lower respiratory problems (cHR = 0.45), and lower hip fractures (cHR = 0.63) than the non-operation group (all < 0.001). After adjustment, the risks for mortality and respiratory problems remained lower (adjusted HR = 0.60 and 0.65, both < 0.001) in the operation than the non-operation group, while hip fractures were indifferent (aHR = 1.08, > 0.05). Therefore, surgery for DSD is invaluable since it could reduce the risks of mortality and of hospitalization for respiratory problems.
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http://dx.doi.org/10.3390/jcm8040483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518357PMC
April 2019

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Neuroimage 2019 05 3;191:537-548. Epub 2019 Mar 3.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Accurate and reliable quantification of brain metabolites measured in vivo using H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.
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http://dx.doi.org/10.1016/j.neuroimage.2019.02.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818968PMC
May 2019

Prognostic factors related to intratumoral hemorrhage in pediatric intracranial germ cell tumors.

J Chin Med Assoc 2019 Feb;82(2):133-137

Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Background: Certain types of pediatric intracranial germ cell tumors (PIGCTs) are prone to intratumoral hemorrhaging (TH) and associated with poor survival outcome. However, the impact of TH on the functional prognosis of patients with PIGCTs has not been well studied. This study aimed to evaluate the clinical and MR findings in PIGCT patients with TH to identify the factors related to patient survival and functional outcome.

Methods: This study included 17 patients diagnosed with PIGCT and TH between 2002 and 2016 and evaluated TH-associated clinical and MR findings. The modified Rankin scale (mRS) was used to evaluate functional outcome, which was poor when mRS ≧ 3. The volumes of hematomas and tumors were manually tracked within each brain magnetic resonance imaging slice.

Results: Among the 17 patients, 6 (35.3%) died and 9 (52.9%) had poor functional outcome. Regarding the functional outcome, the mean hematoma volume to tumor volume ratio (HTVR) was 8.5 ± 3.9% in the favorable outcome group and 42.3 ± 27.8% in the poor outcome group (p = 0.001). For the survival outcome, the mean HTVR was 15.7 ± 16.1% in the living group and 46.0 ± 31.5% in the deceased group (p = 0.016). The cutoff point of the receiver operating characteristics curve for HTVR to predict death and poor functional outcome was 19.27% and 16.8%, respectively.

Conclusion: Our study demonstrated that patients with larger HTVR had significantly worse functional and survival outcomes than those with smaller HTVR. We suggest that early and aggressive treatment for PIGCTs in patients with large HTVR can improve their long-term prognosis.
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http://dx.doi.org/10.1097/JCMA.0000000000000015DOI Listing
February 2019

Impaired Efficiency and Resilience of Structural Network in Spinocerebellar Ataxia Type 3.

Front Neurosci 2018 17;12:935. Epub 2018 Dec 17.

Institute of Biophotonics and Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Recent studies have shown that the patients with spinocerebellar ataxia type 3 (SCA3) may not only have disease involvement in the cerebellum and brainstem but also in the cerebral regions. However, the relations between the widespread degenerated brain regions remains incompletely explored. In the present study, we investigate the topological properties of the brain networks of SCA3 patients ( = 40) constructed based on the correlation of three-dimensional fractal dimension values. Random and targeted attacks were applied to measure the network resilience of normal and SCA3 groups. The SCA3 networks had significantly smaller clustering coefficients ( < 0.05) and global efficiency ( < 0.05) but larger characteristic path length ( < 0.05) than the normal controls networks, implying loss of small-world features. Furthermore, the SCA3 patients were associated with reduced nodal betweenness ( < 0.001) in the left supplementary motor area, bilateral paracentral lobules, and right thalamus, indicating that the motor control circuit might be compromised. The SCA3 networks were more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization. The SCA3 revealed a more sparsity and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient, and global efficiency and increased value in characteristic path length. The cortico-cerebral circuits in SCA3 were disrupted and segregated into occipital-parietal (visual-spatial cognition) and frontal-pre-frontal (motor control) clusters. The cerebellum of SCA3 were segregated from cerebellum-temporal-frontal circuits and clustered into a frontal-temporal cluster (cognitive control). Therefore, the disrupted structural network presented in this study might reflect the clinical characteristics of SCA3.
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http://dx.doi.org/10.3389/fnins.2018.00935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304428PMC
December 2018

Correlations among brain and spinal MRI findings in spontaneous intracranial hypotension.

Cephalalgia 2018 12 9;38(14):1998-2005. Epub 2018 Oct 9.

2 Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei City, Taiwan.

Objectives: Several brain and spinal magnetic resonance imaging signs have been described in spontaneous intracranial hypotension. Their correlations are not fully studied. This study aimed to explore potential mechanisms underlying cerebral neuroimaging findings and to examine associations among spinal and brain magnetic resonance imaging signs.

Methods: We conducted a retrospective review of magnetic resonance myelography and brain magnetic resonance imaging records of patients with spontaneous intracranial hypotension. Categorical principal component analysis was employed to cluster brain neuroimaging findings. Spearman correlation was employed to analyze associations among different brain neuroimaging findings and between brain and spinal neuroimaging findings.

Results: In patients with spontaneous intracranial hypotension (n = 148), categorical principal component analysis of brain neuroimaging signs revealed two clusters: Cerebral venous dilation and brain descent. Among all brain magnetic resonance imaging signs examined, only midbrain-pons angle associated with anterior epidural cerebrospinal fluid collection length (surrogate spinal cerebrospinal fluid leak severity) (n = 148, Spearman's ρ = -0.38, p < .001). Subgroup analyses showed that the association between midbrain-pons angle (within brain descent cluster) and spinal cerebrospinal fluid leak severity was presented in patients with convex margins of the transverse sinuses (n = 122, Spearman's ρ = -0.43, p < .001), but not in patients without convex margins (n = 26, Spearman's ρ = -0.19, p = .348). The association between severity of transverse sinus distension and spinal cerebrospinal fluid leak severity was only presented in patients without convex margins (n = 26, Spearman's ρ = 0.52, p = .006).

Conclusion: This study indicates that there are two factors behind the brain neuroimaging findings in spontaneous intracranial hypotension: Cerebral venous dilation and brain descent. Certain brain neuroimaging signs correlate with spinal cerebrospinal fluid leakage severity, depending on different circumstances.
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http://dx.doi.org/10.1177/0333102418804161DOI Listing
December 2018

Vascular wall imaging in reversible cerebral vasoconstriction syndrome - a 3-T contrast-enhanced MRI study.

J Headache Pain 2018 Aug 30;19(1):74. Epub 2018 Aug 30.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, 112, Taiwan.

Background: Limited histopathology studies have suggested that reversible cerebral vasoconstriction syndromes (RCVS) does not present with vascular wall inflammation. Previous vascular imaging studies have had inconsistent vascular wall enhancement findings in RCVS patients. The aim of this study was to determine whether absence of arterial wall pathology on imaging is a universal finding in patients with RCVS.

Methods: We recruited patients with RCVS from Taipei Veterans General Hospital prospectively from 2010 to 2012, with follow-up until 2017 (n = 48). We analyzed the characteristics of vascular wall enhancement in these patients without comparisons to a control group. All participants received vascular wall imaging by contrasted T1 fluid-attenuated inversion recovery with a 3-T magnetic resonance machine. The vascular wall enhancement was rated as marked, mild or absent.

Results: Of 48 patients with RCVS, 22 (45.8%) had vascular wall enhancement (5 marked and 17 mild). Demographics, clinical profiles, and cerebral artery flow velocities were similar across patients with versus without vascular wall enhancement, except that patients with vascular wall enhancement had fewer headache attacks than those without (p = 0.04). Follow-up imaging completed in 14 patients (median interval, 7 months) showed reduced enhancement in 9 patients, but persistent enhancement in 5.

Conclusion: Almost half of our RCVS patients exhibited imaging enhancement of diseased vessels, and it was persistent for approximately a third of those patients with follow-up imaging. Both acute and persistent vascular wall enhancement may be unhelpful for differentiating RCVS from central nervous system vasculitis or subclinical atherosclerosis.
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http://dx.doi.org/10.1186/s10194-018-0906-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117223PMC
August 2018

Dynamic Changes in White Matter Hyperintensities in Reversible Cerebral Vasoconstriction Syndrome.

JAMA Neurol 2018 09;75(9):1106-1113

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Importance: White matter hyperintense lesions (WMHs) are highly prevalent in patients with reversible cerebral vasoconstriction syndrome (RCVS); however, their characteristics and underlying pathophysiology are unclear.

Objective: To investigate the spatiotemporal distribution and pathomechanisms of WMHs in patients with RCVS.

Design, Setting, And Participants: We prospectively recruited patients with RCVS over a 3-year period from January 2010 through December 2012 from the headache center or emergency department of Taipei Veterans General Hospital, Taipei, Taiwan, a 2947-bed national medical center. In total, 85 patients with RCVS were approached, of whom 4 declined to participate, 5 declined follow-up scans, 6 were lost to follow-up, and 5 had suboptimal images. Patients received serial isotropic 3-dimension fluid-attenuated inversion recovery sequence imaging (1-mm slice thickness) with a 3-T magnetic resonance imaging machine as well as transcranial and extracranial color-coded sonography on registration and during follow-ups (at 1 and 2 months, with variations adapting to clinical condition). Data were analyzed from January 2015 to May 2017.

Main Outcomes And Measures: The fluid-attenuated inversion recovery lesion segmentation toolbox was used to segment WMHs automatically. The WMHs were classified as periventricular or deep and were segmented into 13 anatomical locations. The neuroimaging scientists who executed the program were blinded to clinical information. Vascular parameters, including the Lindegaard index (vasoconstriction severity), pulsatility index, and resistance index of the internal carotid artery, were independently collected for comparison.

Results: Sixty-five patients with RCVS completed the study and underwent a total of 162 magnetic resonance imaging examinations. Of the 65 included patients, 58 (89%) were women, and the mean (SD) age was 50.1 (8.9) years. The total mean (SD) WMH load peaked at 3.2 (4.4) cm3 in the third week postonset and fell to 0.8 (0.6) cm3 in the fourth week. White matter hyperintensities were predominantly frontal and periventricular. White matter hyperintensity load correlated strongly with Lindegaard index during the second week of the disease course (r = 0.908; P < .001) and also correlated with the pulsatility index and resistance index of the internal carotid artery.

Conclusions And Relevance: White matter hyperintensities in patients with RCVS have a dynamic temporal evolution that parallels disease severity. The finding of partially reversible WMHs deserves attention and should be known by clinicians taking care of patients with RCVS. White matter hyperintensities in RCVS may be attributed, at least partially, to regional hypoperfusion and impaired dampening capacity to central pulsatile flow.
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http://dx.doi.org/10.1001/jamaneurol.2018.1321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143117PMC
September 2018
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