Filling the data gap on CGRP mAb therapy in low- to middle-income countries in Southeast Asia: insights from a real-world study in Thailand.

BACKGROUND: Most real-world data on CGRP mAbs have been published from high-income countries such as the USA, Western countries, Japan, Korea, and Singapore. However, data from low- and middle-income countries in Southeast Asia is lacking. This is the first real-world study from Thailand to describe the efficacy of CGRP mAbs therapy in migraine patients and to analyze the response trends between episodic migraine and chronic migraine. METHODS: We conducted a single-center, real-world retrospective chart review study with an observation period of 6 months after CGRP mAbs initiation. We aim to compare treatment responses to CGRP mAbs between EM and CM patients. RESULTS: A total of 47 Thai patients were enrolled (median [IQR] age 37.2 [28.6-50.4] years; 85.1%F, 44.7% EM; 70.2% galcanezumab). There was no difference in baseline characteristics and migraine disability assessment (MIDAS) between EM and CM. The overall ≥ 30%, ≥ 50%, and ≥ 70% monthly migraine day reduction rates at 6 months were 89.0%, 71.6%, and 58.5% with higher responders in EM. There was a significant decrease in monthly headache days (MHDs) over time (adjusted ß = -0.42, p < 0.001) and a significant decrease in MIDAS score over time after the initiation of CGRP mAbs (adjusted ß = -1.12, p = 0.003). However, there were no differences between the two diagnoses. There was no significant decrease in the number of abortive medication pills used over time after the initiation of CGRP mAbs. CM had a significantly steeper trend compared to those with EM. CONCLUSION: The first real-world study in Thailand demonstrated that CGRP mAbs therapy had efficacy for migraine treatment, as evidenced by a reduction in MHDs, decreased disability, and reduced use of abortive medications. Additionally, the response pattern to CGRP mAbs therapy was similar between EM and CM in terms of MHDs reduction and MIDAS score improvement.

Asynchronous online lecture may not be an effective method in teaching cardiovascular physiology during the COVID-19 pandemic.

BACKGROUND: Asynchronous online lecture has become a common teaching method in medical education, especially during the COVID-19 pandemic. However, the effectiveness and students' attitudes towards this method under this special circumstance have not been exclusively studied. Hence, we aimed to evaluate these aspects of cardiovascular physiology teaching in an undergraduate medical curriculum. METHODS: We analysed and compared the academic achievement and attitudes of 613 medical students on cardiovascular physiology between pre-COVID-19 and COVID-19 years in which different teaching methods were implemented. In addition, we also explored the importance of teaching methods and teachers by subgroup analysis to evaluate whether they influenced the academic achievement and attitudes of students. RESULTS: Overall students' academic achievement was significantly higher when lectures were taught by the traditional method than by the asynchronous online method. Moreover, subgroup analysis revealed that teachers were also a factor influencing students' academic achievement. Although most students had positive attitudes towards asynchronous online lectures, overall satisfaction was slightly higher when all lectures were taught by the traditional method than by the asynchronous online method. CONCLUSIONS: Asynchronous online lectures might not be an effective teaching method especially during the abrupt change in education. Under the 'new normal' medical education, not only teaching methods but also teachers are the essential keys to the success in academic achievement and attitudes of undergraduate medical students.

Pattern of cortical thinning in logopenic progressive aphasia patients in Thailand.

BACKGROUND: Logopenic progressive aphasia (LPA) is an uncommon neurodegenerative disorder primarily characterized by word-finding difficulties and sentence repetition impairment. Prominent cortical atrophy around left temporo-parietal junction (TPJ) is a classical imaging feature of LPA. This study investigated cortical thinning pattern in clinically diagnosed LPA patients using non-demented subjects as a control group. We also aimed to explore whether there was prominent thinning of other cortical area additional to the well-recognized left TPJ. METHODS: Thicknesses of all cortical regions were measured from brain magnetic resonance images using an automated command on Freesurfer software. Cortical thickness of the LPA and control groups were compared by two methods: 1) using a general linear model (GLM) in SPSS software; and 2) using a vertex-by-vertex GLM, performed with Freesurfer's QDEC interface. RESULTS: Besides the well-recognized left TPJ, cortical regions that were significantly thinner in the LPA group by both comparison methods included left caudal middle frontal gyrus (CMFG) (p = 0.006 by SPSS, p = 0.0003 by QDEC), left rostral middle frontal gyrus (p = 0.001 by SPSS, p = 0.0001 by QDEC), left parahippocampal gyrus (p = 0.008 by SPSS, p = 0.005 by QDEC) and right CMFG (p = 0.005 by SPSS, p = 0.0001 by QDEC). CONCLUSIONS: Our results demonstrated that thinning of middle frontal gyri may be an additional feature in clinically diagnosed LPA patients. Involvement of left parahippocampal gyrus may reflect the underlying neuropathology of Alzheimer's disease in majority of the LPA patients.

The concept-sharing approach: a teaching strategy to promote objective-oriented learning and academic performance in medical students.

Traditionally teachers display the learning outline at the beginning and conclusions at the end of didactic teaching sessions, and students may find it difficult to understand how teaching activities relate to learning objectives and what they should study for assessments. We introduced the "concept-sharing approach" in our neurophysiology course. This approach explicates how the content relates with learning objectives throughout the entirety of each teaching session to help the students assimilate the learning material and direct their learning in an objective-orientated way. In this study, we aimed to examine satisfaction of the concept-sharing approach in medical students and to investigate the relationship between student perception of this teaching strategy and academic performance. The results demonstrated that most participants (74.1%) had a positive impression of this teaching strategy at the end of the course, which was significantly >50.7% at the beginning of the course (P < 0.001). The participants who agreed the concept-sharing approach was useful had significantly higher final assessment (P = 0.014) and end-of-course formative assessment scores (P = 0.001). The findings indicate that after experiencing this new teaching approach, medical students appreciate its utility and that students who engage with this approach are more likely to perform well in assessments. In summary, the concept-sharing approach is a simple teaching strategy which was favored by students and may promote academic performance.

Two-dimensional integration approach to teaching cardiovascular physiology: effectiveness and students' perspectives.

BACKGROUND: Pre-clerkship medical curriculums consist of a series of organ system-based courses and lectures but often lack an integration between organ systems. Such integration could be beneficial for clerkship years and students' future career. Hence, we aimed to share our process of organising an integrative teaching approach in a large class of pre-clerkship medical students and to reflect the students' perspective toward the teaching process in this observational study. In addition, we tested effectiveness of this integrative approach compared with the traditional teaching (lecture). METHODS: We organised a two-dimensional (2D)-integrative teaching for 309 students in selected topics of cardiovascular physiology of the medical curriculum of the Faculty of Medicine, Chulalongkorn University, Thailand. The first dimension of integration is the incorporation of physiology of other organ systems into the cardiovascular physiology class. The second is the integration of multiple teaching methods and strategies, including small group discussion, student presentation, wrap-up, quiz, and question-and-answer sessions. Unless opting out, students evaluated this integrative teaching by filling in a questionnaire. The summative scores were also used to determine their comprehensive understandings of the content. RESULTS: The course evaluation showed that most students (81.9-91.2%) had positive attitudes toward all organised sessions, i.e. this teaching method helps promote their basic and applied physiology knowledge, critical thinking, information searching, presentation, and teamwork skills. In general, students at all performance levels attained higher scores in the summative exam for the 2D-integrative-class-relevant questions (74.4±16.1%) than for the lecture-pertinent questions (65.2±13.6%). CONCLUSIONS: In a large class size of pre-clerkship students, 2D-integrative teaching strategies with careful planning and preparation can be successfully implemented, based on positive attitudes and relatively high summative scores of students in this study. Hence, this comprehensive teaching could be incorporated in current medical curriculums, particularly for the complex learning topics.

Attitude, but not self-evaluated knowledge, correlates with academic performance in physiology in Thai medical students.

Positive attitude and self-evaluation are necessary for medical students and doctors. To explore how best to integrate physiology teaching in our Thai medical curriculum, we investigated relationships between student's academic performance, their attitude, self-evaluated knowledge, and proportion of physiology taught in an organ-system integrated block. We organized 13 physiology laboratory classes, during which students self-rated attitude and knowledge. Academic performance was measured by formative and summative assessments. One hundred thirty-six participants were categorized into most proactive (Most PA), more proactive (More PA), less proactive (Less PA), and least proactive (Least PA) attitude groups by self-preparation questionnaire. Eighty participants were categorized into high (HighE), moderate (ModerateE), and low (LowE) self-evaluation rating groups. Mean formatives score in the Most PA group was significantly higher than in the other PA groups (P = 0.003, P = 0.001, and P < 0.001, respectively). Mean summative score in the Most PA group was significantly higher than the Less PA and the Least PA groups (P = 0.017 and P = 0.015 respectively). There was no significant difference in mean assessment scores among HighE, ModerateE, and LowE groups. Proportion of teaching time dedicated to physiology positively correlated with student attitude (r = 0.84, P = 0.001) and negatively correlated with self-evaluation rating (r = -0.73, P = 0.007). Thai medical students may benefit from a proactive attitude to studying physiology, contrasting with traditional didactic expectations of Thai education. Proportion of teaching time dedicated to physiology does not influence academic performance; therefore, future adjustments to curriculum integration may incorporate classes that facilitate self-directed learning. Future study should explore other influences on learning and assessment performance.

A SUNCT-like headache associated with lateral pontine infarction - case series and systematic review.

BACKGROUND AND AIM: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and autonomic symptoms (SUNA) are trigeminal autonomic cephalalgias (TACs). The study explores the potential association between SUNCT/SUNA-like headaches and lateral pontine infarctions. METHODS: Case series and systematic review. RESULTS: We present three cases diagnosed with SUNCT following lateral pontine infarction on magnetic resonance imaging (MRI), along with a review of these cases and 10 others from the literature. DISCUSSION AND CONCLUSION: This review suggests a connection between SUNCT/SUNA-like symptoms and lateral pontine infarctions. The section also delves into the anatomy and pathophysiology of these symptoms, proposing a mechanism involving neural pathway remodelling in the lateral brainstem.

Levodopa-induced dyskinesia in early-onset Parkinson's disease (EOPD) associates with glucocerebrosidase mutation: A next-generation sequencing study in EOPD patients in Thailand.

BACKGROUND: With the benefit of using next-generation sequencing (NGS), our aim was to examine the prevalence of known monogenic causes in early-onset Parkinson's disease (EOPD) patients in Thailand. The association between clinical features, such as levodopa-induced dyskinesia (LID), and genotypes were also explored. METHOD: NGS studies were carried out for EOPD patients in the Tertiary-referral center for Parkinson's disease and movement disorders. EOPD patients who had LID symptoms were enrolled in this study (n = 47). We defined EOPD as a patient with onset of PD at or below 50 years of age. LID was defined as hyperkinetic movements including chorea, ballism, dystonia, myoclonus, or any combination of these movements resulting from levodopa therapy, which could be peak-dose, off-period, or diphasic dyskinesias. RESULTS: Pathogenic variants were identified in 17% (8/47) of the Thai EOPD patients, of which 10.6% (5/47) were heterozygous GBA variants (c.1448T>C in 3 patients and c.115+1G>A in 2 patients), 4.3% (2/47) homozygous PINK1 variants (c.1474C>T) and 2.1% (1/47) a PRKN mutation (homozygous deletion of exon 7). The LID onset was earlier in patients with GBA mutations compared to those without (34.8±23.4 vs 106.2±59.5 months after starting levodopa, respectively, p = 0.001). LID onset within the first 30 months of the disease was also found to be independently associated with the GBA mutation (odds ratio [95% confidence interval] = 25.00 [2.12-295.06], p = 0.011). CONCLUSION: Our study highlights the high prevalence of GBA pathogenic variants in Thai patients with EOPD and the independent association of these variants with the earlier onset of LID. This emphasizes the importance of genetic testing in this population.

Student academic performance in non-lecture physiology topics following the abrupt change from traditional on-site teaching to online teaching during COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, pre-clerkship medical education, including all physiology classes, was obliged to change to online teaching due to limitations of on-site (face-to-face) classes. However, the effectiveness of online teaching in non-lecture physiology topics during the COVID-19 pandemic has not been thoroughly investigated. METHOD: We conducted a prospective study to evaluate the students' academic achievement and opinions on online teaching during the COVID-19 academic year. Academic achievement of 312 students in the COVID-19 year was compared with that of 299 students in the pre-COVID-19 year. Student opinions regarding social interactions and the preferred learning method were also collected. RESULTS: We found that student academic achievement in the non-lecture physiology topics, assessed by summative scores, was 4.80±0.92 percent higher in the pre-COVID-19 year than in the COVID-19 year (P < 0.01, Cohen's d = 0.42). Students rated that online classes tended to reduce their interactions with peers and teachers; however, students preferred online learning over traditional on-site learning. CONCLUSIONS: This study pointed out that students' academic performance related to the physiology topics taught by online non-lecture methods during the COVID-19 pandemic was lower than their performance when the topics were taught by the traditional (on-site) methods, although students reported that they preferred the online teaching. Hence, we suggest that medical teachers should deliberately plan and utilise a variety of tools and techniques when developing online non-lecture classes to preserve the interactivity of the classes, which might overcome this gap in students' academic performance.

Monoamine Levels and Parkinson's Disease Progression: Evidence From a High-Performance Liquid Chromatography Study.

Parkinson's disease (PD) is associated with dysfunction of monoamine neurotransmitter systems. We investigated changes in the levels of monoamine and their metabolites in PD patients, together with their association to clinical profiles. PD patients and age-matched control subjects (n = 40 per group) were enrolled. Using high-performance liquid chromatography (HPLC) with an electrochemical detector, levels of monoamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; and serotonin, 5-HT) were measured in plasma, while the metabolites (homovanillic acid, HVA; vanillylmandelic acid, VMA; and 5-hydroxyindoleacetic acid, 5-HIAA) were measured in urine. Plasma DA level was not significantly different between PD and control groups. PD patients had significantly higher plasma NE but lower EPI and 5-HT levels. PD patients had a significantly higher HVA/DA ratio and lower VMA/NE ratio than control subjects, while the 5-HIAA/5-HT ratio was not different between the groups. Regarding the association between monoamine levels and clinical profiles, the DA level had a negative relationship with disease duration and the 5-HT level had a negative relationship with severity of motor impairment. These findings emphasized the involvements of several neurotransmission systems and their association with clinical profiles in PD patients, demonstrated by quantification of monoamine levels in peripheral body fluids. This could benefit appropriate pharmacological treatment planning in respect of monoamine changes and might also help predict subsequent clinical symptoms.

A transformation of trigeminal neuralgia into SUNCT/SUNA: A case report and literature review / Uma transformação da neuralgia do trigêmeo em SUNCT/SUNA: relato de caso e revisão da literatura

Introduction: Trigeminal neuralgia and Short-lasting Unilateral Neuralgiform Headache with Conjunctival injection and Tearing (SUNCT)/Short-lasting Unilateral Neuralgiform Headache Attacks with Cranial Autonomic Symptoms (SUNA) are characterized by similar clinical manifestations, which may lead to diagnostic confusion. However, the transformation of trigeminal neuralgia into SUNCT/SUNA is a rare phenomenon. This report describes a case of trigeminal neuralgia transformation into SUNCT/SUNA due to neurovascular compression and reviews all previously published cases of trigeminal neuralgia to SUNCT/SUNA transformation in the literature. Case presentation: A 49-year-old Thai male patient presented with progressive right facial pain for a period of three months. One year prior, he developed trigeminal neuralgia along the maxillary branch of the trigeminal nerve, characterized by electrical shock-like pain in the right upper molar, exacerbated by eating. His symptoms were effectively managed with carbamazepine. Nine months later, he began experiencing recurrent electrical shock-like pain along the ophthalmic division of the right trigeminal nerve, accompanied by lacrimation, which failed to respond to continued treatment with carbamazepine. Three months prior to presentation, his symptoms evolved into SUNCT/SUNA, characterized by electrical shock-like pain in the right periorbital area and conjunctival injection, lacrimation. Neuroimaging revealed high-grade neurovascular compression of the right trigeminal nerve by the right superior cerebellar artery. The patient's symptoms resolved following microvascular decompression. Conclusion: Clinicians should be aware that patients with longer disease duration of trigeminal neuralgia who develop new neuralgic pain in the ophthalmic branch division with mild autonomic symptoms may be at risk for transformation into SUNCT/SUNA.

Introduction: Trigeminal neuralgia and Short-lasting Unilateral Neuralgiform Headache with Conjunctival injection and Tearing (SUNCT)/Short-lasting Unilateral Neuralgiform Headache Attacks with Cranial Autonomic Symptoms (SUNA) are characterized by similar clinical manifestations, which may lead to diagnostic confusion. However, the transformation of trigeminal neuralgia into SUNCT/SUNA is a rare phenomenon. This report describes a case of trigeminal neuralgia transformation into SUNCT/SUNA due to neurovascular compression and reviews all previously published cases of trigeminal neuralgia to SUNCT/SUNA transformation in the literature. Case presentation: A 49-year-old Thai male patient presented with progressive right facial pain for a period of three months. One year prior, he developed trigeminal neuralgia along the maxillary branch of the trigeminal nerve, characterized by electrical shock-like pain in the right upper molar, exacerbated by eating. His symptoms were effectively managed with carbamazepine. Nine months later, he began experiencing recurrent electrical shock-like pain along the ophthalmic division of the right trigeminal nerve, accompanied by lacrimation, which failed to respond to continued treatment with carbamazepine. Three months prior to presentation, his symptoms evolved into SUNCT/SUNA, characterized by electrical shock-like pain in the right periorbital area and conjunctival injection, lacrimation. Neuroimaging revealed high-grade neurovascular compression of the right trigeminal nerve by the right superior cerebellar artery. The patient's symptoms resolved following microvascular decompression. Conclusion: Clinicians should be aware that patients with longer disease duration of trigeminal neuralgia who develop new neuralgic pain in the ophthalmic branch division with mild autonomic symptoms may be at risk for transformation into SUNCT/SUNA

Human T-Lymphotropic Virus Type-1-Associated Myelopathy/Tropical Spastic Paraparesis: The First Case Report in Southeast Asia.

Human T-lymphotropic virus type-1 (HTLV-1) infection was diagnosed in a Thai patient with chronic progressive myelopathy. The phylogenetic tree of the ltr sequencing of HTLV-1 indicated that the virus belongs to the transcontinental genotype of the cosmopolitan subtype A. This is the first case report of HTLV-1-associated myelopathy in Southeast Asia. Awareness of HTLV-1 and related condition should be encouraged in this region and routine screening should be applied to blood donors.

Cognitive Profile and its Association with Neuroimaging Markers of Non-Demented Cerebral Amyloid Angiopathy Patients in a Stroke Unit.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized. OBJECTIVE: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA. METHODS: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed. RESULTS: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of -1.92±1.56 (mean±SD), then followed by executive function (-0.93±1.01), episodic memory (-0.87±1.29), semantic fluency (-0.73±1.06), and attention (-0.42±0.98). TBV of the CAA patients was correlated with processing speed (ß= 0.335, p = 0.03) and executive function (ß= 0.394, p = 0.01). CONCLUSIONS: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function.

Posterior white matter disease distribution as a predictor of amyloid angiopathy.

OBJECTIVES: We sought to examine whether a posterior distribution of white matter hyperintensities (WMH) is an independent predictor of pathologically confirmed cerebral amyloid angiopathy (CAA) and whether it is associated with MRI markers of CAA, in patients without lobar intracerebral hemorrhage. METHODS: We developed a quantitative method to measure anteroposterior (AP) distribution of WMH. A retrospective cohort of patients without intracerebral hemorrhage and with pathologic evaluation of CAA was examined to determine whether posterior WMH distribution was an independent predictor of CAA (n=59). The relationship of AP distributions of WMH to strictly lobar microbleeds (MBs) (n=259) and location of dilated perivascular spaces (DPVS) (n=85) was examined in a separate cohort of patients evaluated in a memory clinic. RESULTS: A more posterior WMH distribution was found to be an independent predictor of pathologic evidence of CAA (p=0.001, odds ratio [95% confidence interval]=1.19 [1.07-1.32]), even in the subgroup without lobar MBs (p=0.016, odds ratio [95% confidence interval]=1.18 [1.03-1.36]). In the memory clinic cohort, strictly lobar MBs were independently associated with more posterior WMH distribution (p=0.009). AP distribution of WMH was also associated with location of DPVS (p=0.001), in that patients with predominant DPVS in the white matter over the basal ganglia harbored a more posterior WMH distribution. CONCLUSIONS: Our results suggest that AP distribution of WMH may represent an additional marker of CAA, irrespective of the presence of lobar hemorrhages. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that there is a significant association between the AP distribution of WMH on MRI with the presence of pathologically confirmed CAA pathology.