Using machine learning to identify key subject categories predicting the pre-clerkship and clerkship performance: 8-year cohort study.

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data pre-processing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and ten subjects from the basic medical science stage with an area under the ROC curve (AUC) greater than 0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.

Different Splice Isoforms of Peripheral Triggering Receptor Expressed on Myeloid Cells 2 mRNA Expressions are Associated With Cognitive Decline in Mild Dementia Due to Alzheimer's Disease and Reflect Central Neuroinflammation.

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation.

MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II.

Background and objectives: The differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors. Methods: Between January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed. Results: A greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%). Discussion: Discerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Impaired Glymphatic and Meningeal Lymphatic Functions in Patients with Chronic Migraine.

OBJECTIVE: This study was undertaken to investigate migraine glymphatic and meningeal lymphatic vessel (mLV) functions. METHODS: Migraine patients and healthy controls (HCs) were prospectively recruited between 2020 and 2023. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index for glymphatics and dynamic contrast-enhanced magnetic resonance imaging parameters (time to peak [TTP]/enhancement integral [EI]/mean time to enhance [MTE]) for para-superior sagittal (paraSSS)-mLV or paratransverse sinus (paraTS)-mLV in episodic migraine (EM), chronic migraine (CM), and CM with and without medication-overuse headache (MOH) were analyzed. DTI-ALPS correlations with clinical parameters (migraine severity [numeric rating scale]/disability [Migraine Disability Assessment (MIDAS)]/bodily pain [Widespread Pain Index]/sleep quality [Pittsburgh Sleep Quality Index (PSQI)]) were examined. RESULTS: In total, 175 subjects (112 migraine + 63 HCs) were investigated. DTI-ALPS values were lower in CM (median [interquartile range] = 0.64 [0.12]) than in EM (0.71 [0.13], p = 0.005) and HCs (0.71 [0.09], p = 0.004). CM with MOH (0.63 [0.07]) had lower DTI-ALPS values than CM without MOH (0.73 [0.12], p < 0.001). Furthermore, CM had longer TTP (paraSSS-mLV: 55.8 [12.9] vs 40.0 [7.6], p < 0.001; paraTS-mLV: 51.2 [8.1] vs 44.0 [3.3], p = 0.002), EI (paraSSS-mLV: 45.5 [42.0] vs 16.1 [9.2], p < 0.001), and MTE (paraSSS-mLV: 253.7 [6.7] vs 248.4 [13.8], p < 0.001; paraTS-mLV: 252.0 [6.2] vs 249.7 [1.2], p < 0.001) than EM patients. The MIDAS (p = 0.002) and PSQI (p = 0.002) were negatively correlated with DTI-ALPS index after Bonferroni corrections (p < q = 0.01). INTERPRETATION: CM patients, particularly those with MOH, have glymphatic and meningeal lymphatic dysfunctions, which are highly clinically relevant and may implicate pathogenesis for migraine chronification. ANN NEUROL 2024;95:583-595.

Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome.

BACKGROUND: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption. METHODS: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption. RESULTS: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index. CONCLUSIONS: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure.

Negative effects on medical students' scores for clinical performance during the COVID-19 pandemic in Taiwan: a comparative study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has heavily impacted medical clinical education in Taiwan. Medical curricula have been altered to minimize exposure and limit transmission. This study investigated the effect of COVID-19 on Taiwanese medical students' clinical performance using online standardized evaluation systems and explored the factors influencing medical education during the pandemic. METHODS: Medical students were scored from 0 to 100 based on their clinical performance from 1/1/2018 to 6/31/2021. The students were placed into pre-COVID-19 (before 2/1/2020) and midst-COVID-19 (on and after 2/1/2020) groups. Each group was further categorized into COVID-19-affected specialties (pulmonary, infectious, and emergency medicine) and other specialties. Generalized estimating equations (GEEs) were used to compare and examine the effects of relevant variables on student performance. RESULTS: In total, 16,944 clinical scores were obtained for COVID-19-affected specialties and other specialties. For the COVID-19-affected specialties, the midst-COVID-19 score (88.513.52) was significantly lower than the pre-COVID-19 score (90.143.55) (P<0.0001). For the other specialties, the midst-COVID-19 score (88.323.68) was also significantly lower than the pre-COVID-19 score (90.063.58) (P<0.0001). There were 1,322 students (837 males and 485 females). Male students had significantly lower scores than female students (89.333.68 vs. 89.993.66, P=0.0017). GEE analysis revealed that the COVID-19 pandemic (unstandardized beta coefficient=-1.99, standard error [SE]=0.13, P<0.0001), COVID-19-affected specialties (B=0.26, SE=0.11, P=0.0184), female students (B=1.10, SE=0.20, P<0.0001), and female attending physicians (B=-0.19, SE=0.08, P=0.0145) were independently associated with students' scores. CONCLUSION: COVID-19 negatively impacted medical students' clinical performance, regardless of their specialty. Female students outperformed male students, irrespective of the pandemic.

Noninvasive investigations of human glymphatic dynamics in a diseased model.

OBJECTIVES: To explore human glymphatic dynamics in a diseased model via a noninvasive technique. METHODS: Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities. RESULTS: Eleven subjects were analyzed. The cSIs demonstrated early increase (9 min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18 min and decreasing rates after 45 to 54 min. The GBCA was transported centrifugally and completely removed within 961-1086 min after administration. CONCLUSIONS: The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086 min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits. CLINICAL RELEVANCE STATEMENT: Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future. KEY POINTS: • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086 min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively.

Disrupted Brain Functional Status in Patients with Reversible Cerebral Vasoconstriction Syndrome.

OBJECTIVES: The aim of this study was to investigate the functional networks in subjects with reversible cerebral vasoconstriction syndrome (RCVS) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: We prospectively recruited patients with RCVS and healthy controls (HCs) between February 2017 and April 2021. The rs-fMRI data were analyzed using graph theory methods. We compared node-based global and regional topological metrics (Bundle 1) and network-based intranetwork and internetwork connectivity (Bundle 2) between RCVS patients and HCs. We also explored the associations of clinical and vascular (ie, the Lindegaard index, LI) parameters with significant rs-fMRI metrics. RESULTS: A total of 104 RCVS patients and 93 HCs were included in the final analysis. We identified significantly decreased local efficiency of the left dorsal anterior insula (dAI; p = 0.0005) in RCVS patients within 30 days after disease onset as compared to HCs, which improved 1 month later. RCVS patients also had increased global efficiency (p = 0.009) and decreased average degree centrality (p = 0.045), clustering coefficient (p = 0.033), and assortativity values (p = 0.003) in node-based analysis. In addition, patients with RCVS had increased internetwork connectivity of the default mode network (DMN) with the salience (p = 0.027) and dorsal attention (p = 0.016) networks. Significant correlations between LI and regional local efficiency in left dAI (rs = -0.418, p = 0.042) was demonstrated. INTERPRETATION: The significantly lower local efficiency of the left dAI, suggestive of impaired central autonomic modulation, was negatively correlated with vasoconstriction severity, which is highly plausible for the pathogenesis of RCVS. ANN NEUROL 2023;94:772-784.

Clinical and imaging findings for the evaluation of large Rathke's cleft cysts and cystic craniopharyngiomas.

PURPOSE: Large Rathke's cleft cysts (LRCCs) and cystic craniopharyngiomas (CCPs) arise from the same embryological origin and may have similar MR presentations. However, the two tumors have different management strategies and outcomes. This study was designed to evaluate the clinical and imaging findings of LRCCs and CCPs, aiming to evaluate their pretreatment diagnosis and outcomes. METHODS: We retrospectively enrolled 20 patients with LRCCs and 25 patients with CCPs. Both tumors had a maximal diameter of more than 20 mm. We evaluated the patients' clinical and MR imaging findings, including symptoms, management strategies, outcomes, anatomic growth patterns and signal changes. RESULTS: The age of onset for LRCCs versus CCPs was 49.0 ± 16.8 versus 34.2 ± 22.2 years (p = .022); the following outcomes were observed for LRCCs versus CCPs: (1) postoperative diabetes insipidus: 6/20 (30%) versus 17/25 (68%) (p = .006); and (2) posttreatment recurrence: 2/20 (10%) versus 10/25 (40%) (p = .025). The following MR findings were observed for LRCCs versus CCPs: (1) solid component: 7/20 (35%) versus 21/25 (84%) (p = .001); (2) thick cyst wall: 2/20 (10%) versus 12/25 (48%) (p = .009); (3) intracystic septation: 1/20 (5%) versus 8/25 (32%) (p = .030); (4) snowman shape: 18/20 (90%) versus 1/25 (4%) (p < .001); (5) off-midline extension: 0/0 (0%) versus 10/25 (40%) (p = .001); and (6) oblique angle of the sagittal long axis of the tumor: 89.9° versus 107.1° (p = .001). CONCLUSIONS: LRCCs can be differentiated from CCPs based on their clinical and imaging findings, especially their specific anatomical growth patterns. We suggest using the pretreatment diagnosis to select the appropriate surgical approach and thus improve the clinical outcome.

Prevention of in-stent restenosis with drug-eluting balloons in patients with postirradiated carotid stenosis accepting percutaneous angioplasty and stenting.

OBJECTIVE: To investigate the technical safety and outcome of in-stent restenosis (ISR) prevention with drug-eluting balloon (DEB) in patients with postirradiated carotid stenosis (PIRCS) undergoing percutaneous angioplasty and stenting (PTAS). METHODS: Between 2017 and 2021, we prospectively recruited patients with severe PIRCS for PTAS. They were randomly separated into two groups based on endovascular techniques performed with and without DEB. Preprocedural and early postprocedural (within 24 hours) MRI, short-term ultrasonography (6 months after PTAS), and long-term CT angiography (CTA)/MR angiography (MRA), 12 months after PTAS, were performed. Technical safety was evaluated based on periprocedural neurological complications and the number of recent embolic ischemic lesions (REIL) in the treated brain territory on diffusion-weighted imaging of early postprocedural MRI. RESULTS: Sixty-six (30 with and 36 without DEB) subjects were enrolled, with one failure in techniques. For 65 patients in the DEB versus conventional groups, technical neurological symptoms within 1 month (1/29 (3.4%) vs 0/36; P=0.197) and REIL numbers within 24 hours (1.0±2.1 vs 1.3±1.5; P=0.592) after PTAS showed no differences. Peak systolic velocity (PSVs) on short-term ultrasonography was significantly higher in the conventional group (104.13±42.76 vs .81.95±31.35; P=0.023). The degree of in-stent stenosis (45.93±20.86 vs 26.58±8.75; P<0.001) was higher, and there were more subjects (n=8, 38.9% vs 1, 3.4%; P=0.029) with significant ISR (≥ 50%) in the conventional group than in the DEB group on long-term CTA/MRA. CONCLUSIONS: We observed similar technical safety of carotid PTAS with and without DEBs. The number of cases of significant ISR were fewer and the degree of stenosis of ISR was less in primary DEB-PTAS of PIRCS than for conventional PTAS in the 12-month follow-up.

The SIH-EBP Score: A grading scale to predict the response to the first epidural blood patch in spontaneous intracranial hypotension.

BACKGROUND: To develop and validate an easy-to-use scoring system to predict the response to the first epidural blood patching in patients with spontaneous intracranial hypotension. METHODS: This study recruited consecutive patients with spontaneous intracranial hypotension receiving epidural blood patching in a tertiary medical center, which were chronologically divided into a derivation cohort and a validation cohort. In the derivation cohort, factors associated with the first epidural blood patching response were identified by using multivariable logistic regression modeling. A scoring system was developed, and the cutoff score was determined by using the receiver operating characteristic curve. The findings were verified in an independent validation cohort. RESULTS: The study involved 280 patients in the derivation cohort and 78 patients in the validation cohort. The spontaneous intracranial hypotension-epidural blood patching score (range 0-5) included two clinical variables (sex and age) and two radiological variables (midbrain-pons angle and anterior epidural cerebrospinal fluid collections). A score of ≥3 was predictive of the first epidural blood patching response, which was consistent in the validation cohort. Overall, patients who scored ≥3 were more likely to respond to the first epidural blood patching (odds ratio = 10.3). CONCLUSION: For patients with spontaneous intracranial hypotension-epidural blood patching score ≥3, it is prudent to attempt at least one targeted epidural blood patching before considering more invasive interventions.

A single-center, cross-sectional study of cross-professional faculties' perception to virtual class under different scenarios: A stepwise approach.

BACKGROUND: Virtual teaching in medical education is rising with the increased need caused by the recent pandemic. However, evaluations of the perception of clinical teachers across professions for setting a virtual class in different teaching scenarios are limited. This study aims to identify cross-professional clinical teachers' perception of virtual classes and the acceptability of the virtual class-specific checklist for setting a virtual class. METHODS: We conducted a cross-sectional study to investigate clinical teachers' need to set and teach a virtual class and then designed a virtual class-specific checklist with five essential steps and a related training program in July 2021. After the training, 186 participants were randomly enrolled in October 2021 to evaluate their perceptions about setting virtual classes and the acceptability of the virtual class-specific checklist using an online assessment questionnaire. RESULTS: In our institution, the number of faculty-led virtual classes has recently been on the increase. Our study revealed that most teachers agreed that virtual classes could break space and time limitations, but that the Internet environment could affect the fluency of the virtual class. They further agreed that the essential five steps in the checklist should vary depending on the type of teaching scenario. Most clinical teachers, with the exception of those who teach in the operating room, considered the operating room as the most difficult scenario for setting virtual classes. CONCLUSION: Faculty training for setting virtual classes is essential, and the essential virtual class-specific five steps are suitable for different teachers and teaching scenarios. However, the virtual class-specific checklist should be further adjusted according to the limitations caused by emerging innovative virtual teaching technology.

Radiological hints for differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia.

Differentiation cerebellar multiple systemic atrophy (MSA-C) from spinocerebellar ataxia (SCA) is important. The "hot cross bun" sign (HCBS) at pons and magnetic resonance spectroscopy (MRS) are helpful. However, the prevalence of HCBS and the alteration of cerebellar MRS parameters are evolving with disease progression. We hypothesized that since the HCBS and MRS are evolving with time, different parameters for differentiation of MSA-C and SCA are required at different disease stages. The aim of this study was to evaluate the HCBS and MRS changes in patients with MSA-C and SCA at different disease stages. A total of 398 patients with molecularly confirmed SCA (SCA1, 2, 3, 6, 17) and 286 patients diagnosed with probable MSA-C (without mutations in SCA1, 2, 3, 6, 17 genes), who had received brain magnetic resonance imaging (MRI) and MRS from January 2000 to January 2020, were recruited. Twenty-five patients were molecularly identified as having SCA1, 68 as SCA2, 253 as SCA3, 34 as SCA6, and 18 as SCA17. We compared their clinical parameters and neuroimaging features at different disease stages. The presence of HCBS was assessed using an axial T2 fast spin-echo or FLAIR sequence. Proton MRS was recorded with voxel of interest focusing on cerebellar hemispheres and cerebellar vermis and avoiding cerebrospinal fluid spaces space using a single-voxel stimulated echo acquisition mode sequence. We found that patients with MSA-C tend to have a higher prevalence of pontine HCBS, worse Scale for the Assessment and Rating of Ataxia scores, lower cerebellar N-acetyl aspartate (NAA)/creatinine (Cr), and choline (Cho)/Cr, compared to patients with SCA at corresponding disease stages. In MSA-C patients with a disease duration < 1 year and without pontine HCBS, a cerebellar NAA/Cr ≤ 0.79 is a good indicator of the possibility of MSA-C. By using the pontine HCBS and cerebellar MRS, discerning MSA-C from SCA became possible. This study provides cutoff values of MRS to serve as clues in differentiating MSA-C from SCAs.

Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy.

OBJECTIVE: Cerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma-related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long-term seizure outcomes of medical and surgical treatment strategies. METHODS: This was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007-2011 and followed up for 93.6 months on average. The patients were divided into drug-resistant epilepsy (DRE; n = 29), non-DRE (n = 45), and no epilepsy (NE; n = 61). RESULTS: Temporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%, n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%, n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course. SIGNIFICANCE: Temporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long-term seizure outcomes in patients with DRE.

Shortened cerebral circulation time correlates with seizures in brain arteriovenous malformation: a cross-sectional quantitative digital subtraction angiography study.

OBJECTIVE: Seizure is the most common clinical presentation in patients with nonhemorrhagic brain arteriovenous malformations (BAVMs) and it influences their quality of life. Angioarchitectural analysis of the seizure risk for BAVMs is subjective and does not consider hemodynamics. This study aimed to investigate the angioarchitectural and hemodynamic factors that may be associated with seizure in patients with BAVMs. METHODS: From 2011 to 2019, 104 patients with supratentorial BAVMs without previous hemorrhage or treatment were included and grouped according to the initial presentation of seizure. Their angiograms and MRI results were analyzed for morphological characteristics and quantitative digital subtraction angiography (QDSA) parameters. Modified cerebral circulation time (mCCT) was defined as the difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and the parietal vein on lateral DSA. Logistic regression analysis was performed to estimate the odds ratio (OR) for BAVMs presenting with seizure. RESULTS: The seizure group had shorter mCCT (1.98 s vs. 2.44 s, p = 0.005) and more BAVMs with temporal location (45% vs. 30.8%, p = 0.013), neoangiogenesis (55% vs. 33%, p = 0.03), and long draining veins (95% vs. 72%, p = 0.004) than did the nonseizure group. Shorter mCCT (OR: 3.4, p = 0.02), temporal location (OR: 13.4, p < 0.001), and neoangiogenesis (OR: 4.7, p = 0.013) were independently associated with higher risks of seizure, after adjustments for age, gender, BAVM volume, and long draining vein. CONCLUSIONS: Shorter mCCT, temporal location, and neoangiogenesis were associated with epileptic BAVMs. QDSA can objectively evaluate hemodynamic changes in epileptic BAVMs. KEY POINTS: • Quantitative digital subtraction angiography may be used to evaluate the hemodynamic differences between brain arteriovenous malformations presenting with and without seizure. • BAVMs with temporal location, neoangiogenesis, and shortened cerebral circulation time were more likely to present with seizure.

Mutation screening and association analysis of NOTCH3 p.R544C in patients with migraine with or without aura.

BACKGROUND: The role of the NOTCH3 p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown. METHODS: Migraine patients (n = 2,884) (2,279F/605M, mean age 38.8 ± 11.7 years), including 324 (11.2%) with migraine with aura, were prospectively enrolled by headache specialists according to the International Classification of Headache Disorders criteria. These patients and 3,502 population controls free of stroke, dementia, and headache were genotyped for NOTCH3 p.R544C by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Clinical manifestations and brain magnetic resonance images were examined and compared between migraine patients with and without NOTCH3 p.R544C. RESULTS: Thirty-two migraine patients (1.1%) and 36 controls (1.0%) harbored the p.R544C variant, and the percentages were comparable among migraine patients without and with aura, and controls (1.2%, vs. 0.6% vs. 1.0%, p = 0.625). Overall, migraine patients with and without the p.R544C variant had similar percentages of migraine with aura, headache characteristics, frequencies and disabilities. However, those with p.R544C were less likely to have pulsatile headaches (50.0% vs. 68.2%, p = 0.028), and more likely to have moderate to severe white matter hyperintensities in the external capsule (18.8% vs. 1.2%, p = 0.006) and anterior temporal lobe (12.5% vs. 0%, p = 0.008). CONCLUSIONS: Our findings suggest that NOTCH3 p.R544C does not increase the risk of migraine with aura, or migraine as a whole, and generally does not alter clinical manifestations of migraine. The role of NOTCH3 variants, as well as potential influences from ethnicity or modifier genes, in migraine needs to be further clarified.

The Use of Neuroimaging for Predicting Sumatriptan Treatment Response in Patients With Migraine.

OBJECTIVES: To identify the neuroimaging predictors for the responsiveness of patients to sumatriptan and use an independent cohort for external validation. METHODS: Structuralized headache questionnaire and 3-Tesla brain magnetic resonance imaging were performed in migraine patients. Regional brain volumes were automatically calculated using FreeSurfer version 6.0, including bilateral amygdala, anterior cingulated cortex, caudate, putamen, precuneus, orbitofrontal cortex, superior frontal gyri, middle frontal gyri, hippocampus, and parahippocampus. A sumatriptan-responder was defined as headache relief within 2 h after the intake of sumatriptan in at least two out of three treated attacks. We constructed a prediction model for sumatriptan response using the regional brain volume and validated it with an independent cohort of migraine patients. RESULTS: A total of 105 migraine patients were recruited, including 73 sumatriptan responders (69.5%) and 32 (30.5%) non-responders. We divided the migraine patients into derivation (n = 73) and validation cohorts (n = 32). In the derivation cohort, left hippocampal volume was larger in sumatriptan responders (responders vs. non-responders: 3,929.5 ± 403.1 vs. 3,611.0 ± 389.9 mm3, p = 0.002), and patients with a larger left hippocampal volume had a higher response rate to sumatriptan (>4,036.2 vs. ≤4,036.2 mm3: 92.0 vs. 56.3%, p = 0.001). Based on the findings, we constructed a prediction model using the cutoff value of 4,036.2 mm3, and we found that patients with a left hippocampal volume >4,032.6 mm3 had a higher response rate to sumatriptan than those with a left hippocampal volume ≤4,032.6 mm3 (84.6 vs. 42.1%, odds ratio [OR] = 7.6 [95% confidence interval = 1.3-44.0], p = 0.013) in the validation cohort. CONCLUSION: Our study showed that left hippocampal volume is helpful to identify sumatriptan non-responders. This proof-of-concept study shows that left hippocampal volume could be used to predict the treatment response to sumatriptan in migraine patients.

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

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.