Jong-ling Fuh - Academia.edu (original) (raw)

Papers by Jong-ling Fuh

Headache, Jan 13, 2016

-The link between arterial thromboembolism and migraine is well-documented; however, few studies ... more -The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. -We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. -During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92-1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40-4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.

PloS one, 2016

To validate the three time-difference neuropsychological protocols developed by the National Inst... more To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI) in Mandarin-speaking subjects and to investigate the clinical application of the shortest form. Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC) analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening. Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control grou...

Cephalalgia : an international journal of headache, Jan 26, 2016

The association between migraine and the incidence of ischemic stroke varies in different subgrou... more The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Both cohorts (n = 119,017 each) were followed for a mean period of 3.6 ± 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. ...

Journal of the Chinese Medical Association : JCMA, Jan 10, 2016

Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulatio... more Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long-lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocols. This pilot study investigated whether continuous theta burst stimulation (cTBS) on the primary motor cortex reduced headache frequency in patients with migraine. Nine patients with migraine were recruited into our study. All patients received 20 cTBS sessions (bursts of 3 50-Hz TMS pulses at 200-ms intervals for 40 seconds), administered every weekday for 4 consecutive weeks. All patients kept headache diaries for 4 weeks before stimulation (baseline; T1), during stimulation (T2), and 4 weeks after stimulation (T3). The primary outcome measures were the changes of total headache and migraine days from baseline (Wilcoxon signed-rank test; T2 and T3 vs. T1). The number of total headache days was reduced at T2 and T3 co...

Cephalalgia : an international journal of headache, Jan 6, 2016

The objective of this article is to investigate the neurological substrates associated with medic... more The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM). We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses. A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at ...

Cephalalgia : an international journal of headache, Jan 20, 2015

The objectives of this article are to evaluate the association between migraine and trigeminal ne... more The objectives of this article are to evaluate the association between migraine and trigeminal neuralgia and to investigate the effects of age, sex, migraine subtype, and comorbid risk factors on trigeminal neuralgia development. This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Individuals aged ≥ 20 years with neurologist-diagnosed migraine between 2005 and 2009 were included. A non-headache age-, sex-, and propensity score-matched control cohort was selected for comparison. All participants were followed until the end of 2010, death, or the occurrence of trigeminal neuralgia. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for comparison of the risk of trigeminal neuralgia between groups. Both cohorts (n = 137,529 each) were followed for a mean of 3.1 years. During the follow-up period, 575 patients (421,581 person-years) in the migraine cohort ...

Cephalalgia : an international journal of headache, Jan 6, 2015

Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). Th... more Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci (MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of...

Journal of Pain Research, 2015

Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzhe... more Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzheimer's disease (AD). While the exact pathogenesis of AD remains unknown, it potentially involves specific proteins (eg, amyloid beta and tau) and neuroinflammation. A growing body of preclinical evidence also suggests that anesthetic agents interact with the components that mediate AD neuropathology at multiple levels. However, it remains unclear whether anesthesia and surgery are associated with an increased risk of AD in humans. To date, there have not been randomized controlled trials to provide evidence for such a causal relationship. Besides, observational studies showed inconsistent results. A meta-analysis of 15 case-control studies revealed no statistically significant association between general anesthesia and the development of AD (pooled odds ratio [OR] =1.05; P=0.43). However, a few retrospective cohort studies have demonstrated that exposure to anesthesia and surgery is associated with an increased risk of AD. Thus, well-designed studies with longer follow-up periods are still needed to define the role of anesthesia in relation to the development of AD.

Ophthalmology, Jan 9, 2015

To determine whether migraine is associated with an increased risk of developing ocular motor cra... more To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Nationwide retrospective cohort study. Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score-matched controls (n = 138 907). Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P...

PLOS ONE, 2015

Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was corre... more Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was correlated with cognitive and non-cognitive symptoms in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients are unclear. Patients with probable AD and MCI from a medical center outpatient clinic received attention, memory, language, executive function evaluation and Mini-Mental Status Examination (MMSE). The severity of dementia was rated by the Clinical Dementia Rating (CDR) Sum of Box (CDR-SB). The neuropsychiatric inventory (NPI) subscale of agitation/aggression and mood symptoms was also applied. Magnetic resonance imaging (MRI) was scored visually for the MTA, PA and white matter hyperintensity (WMH) scores. We recruited 129 AD and 31 MCI (mean age 78.8 years, 48% female) patients. MMSE scores, memory, language and executive function were all significantly decreased in individuals with AD than those with MCI (p < 0.01). MTA and PA scores reflected significant atrophy in AD compared to MCI; however, the WMH scores did not differ. The MTA scores were significantly correlated with the frontal, parieto-occipital and global WMH scores (p < 0.01) while the PA scores showed a correlation with the parieto-occipital and temporal WMH scores (p < 0.01). After adjusting for age, education, APOE4 gene and diagnostic group covariates, the MTA scores showed a significant association with MMSE and CDR-SB, while the right side PA scores were significantly associated with NPI-agitation/aggression subscales (p < 0.01). Regional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom.

PloS one, 2015

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADAS... more Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal in...

PLOS ONE, 2015

Family caregivers may not agree with patients with dementia regarding attitudes toward end-of-lif... more Family caregivers may not agree with patients with dementia regarding attitudes toward end-of-life preferences, and the effects of this type of disagreement are not well understood. This study sought to identify such a disagreement and its predictors. A cross-sectional sample of 84 family caregivers and patients with dementia was recruited from memory clinics. We used the Mini-Mental State Examination, Neuropsychiatric Inventory, Clinical Dementia Rating, and Katz index of independence in activities of daily living to assess patient symptoms, functions, and severity of dementia. Caregivers completed questionnaires on perceived patient end-of-life care preferences, caregiver end-of-life care preferences for patients, Zarit Burden Interview (ZBI), Center for Epidemiological Studies-Depression Scale (CES-D), and knowledge of clinical complications of advanced dementia. The self-disclosure rates of patient preferences were 34.5% for tube feeding, 39.3% for cardiopulmonary resuscitation, and 45.2% for mechanical ventilation. For patients who had disclosed preferences, the disagreement rate between them and their caregivers was 48.3% for tube feeding, 48.5% for cardiopulmonary resuscitation, and 60.3% for mechanical ventilation. Caregiver depression (i.e., CES-D ≥16) was associated with disagreements on cardiopulmonary resuscitation (adjusted odds ratio (aOR) = 6.6, 95% CI = 1.4-31.1, P = 0.01) and mechanical ventilation (aOR = 14, 95% CI = 2.2-87.2, P = 0.005) preferences. The preferences of end-of-life issues differed greatly between dementia patients and their caregivers. Depression in caregivers is associated with such discrepancy.

Journal of the Chinese Medical Association, 2015

Cephalalgia : an international journal of headache, Jan 20, 2015

Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between... more Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between these two episodic disorders remains elusive. The current study investigated the temporal relationship between migraine and RLS attacks. Migraine patients with RLS were recruited from a headache clinic. Patients with symptomatic RLS, RLS mimics, daily headaches, or daily RLS attacks were excluded. The patients recorded their headaches and RLS attacks for two weeks in a diary. The severity of each headache or RLS attack was rated on a four-point (0-3) Likert scale. Logit-normal, random-effects models were employed to estimate the odds ratios (ORs) for the temporal association between migraine and RLS attacks. Thirty migraine patients with RLS (28 F/2 M, mean age 35.5 ± 9.0 years) completed the study. On the basis of 420 daily diary records, migraine attacks were associated with subsequent RLS attacks occurring on the same and next nights (OR = 6.94, 95% confidence interval (CI) = 4.39-11...

BACKGROUND AND PURPOSE: Bilateral engorged superior ophthalmic veins (SOV) have been reported in ... more BACKGROUND AND PURPOSE: Bilateral engorged superior ophthalmic veins (SOV) have been reported in patients with diffuse brain swelling. We investigated the relationship between the diameter of the SOV on brain MR images and the intracranial pressure (ICP). METHODS: We reviewed the medical records of neurologic inpatients who had undergone both MR imaging of the brain and lumbar puncture. MR imaging

Neurorehabilitation and neural repair, Jan 24, 2014

Obstacle crossing is a balance-challenging task and can cause falls in people with Parkinson'... more Obstacle crossing is a balance-challenging task and can cause falls in people with Parkinson's disease (PD). However, programs for people with PD that effectively target obstacle crossing and dynamic balance have not been established. To examine the effects of virtual reality-based exercise on obstacle crossing performance and dynamic balance in participants with PD. Thirty-six participants with a diagnosis of PD (Hoehn and Yahr score ranging 1 to 3) were randomly assigned to one of three groups. In the exercise groups, participants received virtual reality-based Wii Fit exercise (VRWii group) or traditional exercise (TE group) for 45 minutes, followed by 15 minutes of treadmill training in each session for a total of 12 sessions over 6 weeks. Participants in the control group received no structured exercise program. Primary outcomes included obstacle crossing performance (crossing velocity, stride length, and vertical toe obstacle clearance) and dynamic balance (maximal excursi...

The Journal of Headache and Pain, 2015

Background: Researches to date on the association between headache and weather have yielded incon... more Background: Researches to date on the association between headache and weather have yielded inconsistent results. Only a limited number of studies have examined the clinical significance of self-reported weather sensitivity. This study aimed to identify the difference in the association of headache with temperature between migraine patients with and without temperature sensitivity. Methods: 66 migraine patients (75.8 % female; mean age 43.3 ± 12.9 years) provided their 1-year headache diaries from 2007 to a headache clinic in Taipei, Taiwan. 34 patients (51.5 %) reported sensitivity to temperature change but 32 (48.5 %) did not. Time series of daily headache incidence was modeled and stratified by temperature sensitivity. Empirical mode decomposition was used to identify temporal weather patterns that were correlated to headache incidence, and regression analysis was used to examine the amount of variance in headache incidence that could be explained by temperature in different seasons. Results: Among all migraine patients, temperature change accounted for 16.5 % of variance in headache incidence in winter and 9.6 % in summer. In winter, the explained variance increased to 29.2 % among patients with temperature sensitivity, but was not significant among those without temperature sensitivity. Overall, temperature change explained 27.0 % of the variance of the mild headache incidence but only 4.8 % of the incidence of moderate to severe headache during winter. Conclusions: This diary-based study provides evidence to link the perception of temperature sensitivity and headache incidence in migraine patients. Those who reported temperature sensitivity are more likely to have headache increase during the winter, particular for mild headaches.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medica- tions c... more The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medica- tions currently used for acute migraine attacks in Taiwan according to the principles of evidence-based med- icine. We have assessed the quality of clinical trials, levels of evidence, and referred to other treatment guidelines proposed by Western countries and Japan. After several panel discussions, we merged opinions from

Cephalalgia : an international journal of headache, Jan 17, 2015

Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine... more Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine attacks, but shares other visual deficits in between attacks with migraine without aura (MO). Here, we seek to determine if abnormalities specific to interictal MA patients exist in functional brain connectivity of intrinsic cognitive networks. In particular, these networks are involved in top-down modulation of visual processing. Using resting-state functional magnetic resonance imaging, whole-brain functional connectivity maps were derived from seeds placed in the anterior insula and the middle frontal gyrus, key nodes of the salience and dorsal attention networks, respectively. Twenty-six interictal MA patients were compared with 26 matched MO patients and 26 healthy matched controls. The major findings were: connectivity between the anterior insula and occipital areas, including area V3A, was reduced in MA but not in MO. Connectivity changes between the anterior insula and occipital...

Journal of neurology, neurosurgery, and psychiatry, 2015

Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (... more Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH. Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed. Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-...

Headache, Jan 13, 2016

-The link between arterial thromboembolism and migraine is well-documented; however, few studies ... more -The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. -We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. -During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92-1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40-4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.

PloS one, 2016

To validate the three time-difference neuropsychological protocols developed by the National Inst... more To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI) in Mandarin-speaking subjects and to investigate the clinical application of the shortest form. Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC) analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening. Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control grou...

Cephalalgia : an international journal of headache, Jan 26, 2016

The association between migraine and the incidence of ischemic stroke varies in different subgrou... more The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Both cohorts (n = 119,017 each) were followed for a mean period of 3.6 ± 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. ...

Journal of the Chinese Medical Association : JCMA, Jan 10, 2016

Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulatio... more Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long-lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocols. This pilot study investigated whether continuous theta burst stimulation (cTBS) on the primary motor cortex reduced headache frequency in patients with migraine. Nine patients with migraine were recruited into our study. All patients received 20 cTBS sessions (bursts of 3 50-Hz TMS pulses at 200-ms intervals for 40 seconds), administered every weekday for 4 consecutive weeks. All patients kept headache diaries for 4 weeks before stimulation (baseline; T1), during stimulation (T2), and 4 weeks after stimulation (T3). The primary outcome measures were the changes of total headache and migraine days from baseline (Wilcoxon signed-rank test; T2 and T3 vs. T1). The number of total headache days was reduced at T2 and T3 co...

Cephalalgia : an international journal of headache, Jan 6, 2016

The objective of this article is to investigate the neurological substrates associated with medic... more The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM). We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses. A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at ...

Cephalalgia : an international journal of headache, Jan 20, 2015

The objectives of this article are to evaluate the association between migraine and trigeminal ne... more The objectives of this article are to evaluate the association between migraine and trigeminal neuralgia and to investigate the effects of age, sex, migraine subtype, and comorbid risk factors on trigeminal neuralgia development. This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Individuals aged ≥ 20 years with neurologist-diagnosed migraine between 2005 and 2009 were included. A non-headache age-, sex-, and propensity score-matched control cohort was selected for comparison. All participants were followed until the end of 2010, death, or the occurrence of trigeminal neuralgia. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for comparison of the risk of trigeminal neuralgia between groups. Both cohorts (n = 137,529 each) were followed for a mean of 3.1 years. During the follow-up period, 575 patients (421,581 person-years) in the migraine cohort ...

Cephalalgia : an international journal of headache, Jan 6, 2015

Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). Th... more Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci (MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of...

Journal of Pain Research, 2015

Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzhe... more Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzheimer's disease (AD). While the exact pathogenesis of AD remains unknown, it potentially involves specific proteins (eg, amyloid beta and tau) and neuroinflammation. A growing body of preclinical evidence also suggests that anesthetic agents interact with the components that mediate AD neuropathology at multiple levels. However, it remains unclear whether anesthesia and surgery are associated with an increased risk of AD in humans. To date, there have not been randomized controlled trials to provide evidence for such a causal relationship. Besides, observational studies showed inconsistent results. A meta-analysis of 15 case-control studies revealed no statistically significant association between general anesthesia and the development of AD (pooled odds ratio [OR] =1.05; P=0.43). However, a few retrospective cohort studies have demonstrated that exposure to anesthesia and surgery is associated with an increased risk of AD. Thus, well-designed studies with longer follow-up periods are still needed to define the role of anesthesia in relation to the development of AD.

Ophthalmology, Jan 9, 2015

To determine whether migraine is associated with an increased risk of developing ocular motor cra... more To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Nationwide retrospective cohort study. Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score-matched controls (n = 138 907). Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P...

PLOS ONE, 2015

Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was corre... more Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was correlated with cognitive and non-cognitive symptoms in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients are unclear. Patients with probable AD and MCI from a medical center outpatient clinic received attention, memory, language, executive function evaluation and Mini-Mental Status Examination (MMSE). The severity of dementia was rated by the Clinical Dementia Rating (CDR) Sum of Box (CDR-SB). The neuropsychiatric inventory (NPI) subscale of agitation/aggression and mood symptoms was also applied. Magnetic resonance imaging (MRI) was scored visually for the MTA, PA and white matter hyperintensity (WMH) scores. We recruited 129 AD and 31 MCI (mean age 78.8 years, 48% female) patients. MMSE scores, memory, language and executive function were all significantly decreased in individuals with AD than those with MCI (p < 0.01). MTA and PA scores reflected significant atrophy in AD compared to MCI; however, the WMH scores did not differ. The MTA scores were significantly correlated with the frontal, parieto-occipital and global WMH scores (p < 0.01) while the PA scores showed a correlation with the parieto-occipital and temporal WMH scores (p < 0.01). After adjusting for age, education, APOE4 gene and diagnostic group covariates, the MTA scores showed a significant association with MMSE and CDR-SB, while the right side PA scores were significantly associated with NPI-agitation/aggression subscales (p < 0.01). Regional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom.

PloS one, 2015

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADAS... more Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal in...

PLOS ONE, 2015

Family caregivers may not agree with patients with dementia regarding attitudes toward end-of-lif... more Family caregivers may not agree with patients with dementia regarding attitudes toward end-of-life preferences, and the effects of this type of disagreement are not well understood. This study sought to identify such a disagreement and its predictors. A cross-sectional sample of 84 family caregivers and patients with dementia was recruited from memory clinics. We used the Mini-Mental State Examination, Neuropsychiatric Inventory, Clinical Dementia Rating, and Katz index of independence in activities of daily living to assess patient symptoms, functions, and severity of dementia. Caregivers completed questionnaires on perceived patient end-of-life care preferences, caregiver end-of-life care preferences for patients, Zarit Burden Interview (ZBI), Center for Epidemiological Studies-Depression Scale (CES-D), and knowledge of clinical complications of advanced dementia. The self-disclosure rates of patient preferences were 34.5% for tube feeding, 39.3% for cardiopulmonary resuscitation, and 45.2% for mechanical ventilation. For patients who had disclosed preferences, the disagreement rate between them and their caregivers was 48.3% for tube feeding, 48.5% for cardiopulmonary resuscitation, and 60.3% for mechanical ventilation. Caregiver depression (i.e., CES-D ≥16) was associated with disagreements on cardiopulmonary resuscitation (adjusted odds ratio (aOR) = 6.6, 95% CI = 1.4-31.1, P = 0.01) and mechanical ventilation (aOR = 14, 95% CI = 2.2-87.2, P = 0.005) preferences. The preferences of end-of-life issues differed greatly between dementia patients and their caregivers. Depression in caregivers is associated with such discrepancy.

Journal of the Chinese Medical Association, 2015

Cephalalgia : an international journal of headache, Jan 20, 2015

Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between... more Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between these two episodic disorders remains elusive. The current study investigated the temporal relationship between migraine and RLS attacks. Migraine patients with RLS were recruited from a headache clinic. Patients with symptomatic RLS, RLS mimics, daily headaches, or daily RLS attacks were excluded. The patients recorded their headaches and RLS attacks for two weeks in a diary. The severity of each headache or RLS attack was rated on a four-point (0-3) Likert scale. Logit-normal, random-effects models were employed to estimate the odds ratios (ORs) for the temporal association between migraine and RLS attacks. Thirty migraine patients with RLS (28 F/2 M, mean age 35.5 ± 9.0 years) completed the study. On the basis of 420 daily diary records, migraine attacks were associated with subsequent RLS attacks occurring on the same and next nights (OR = 6.94, 95% confidence interval (CI) = 4.39-11...

BACKGROUND AND PURPOSE: Bilateral engorged superior ophthalmic veins (SOV) have been reported in ... more BACKGROUND AND PURPOSE: Bilateral engorged superior ophthalmic veins (SOV) have been reported in patients with diffuse brain swelling. We investigated the relationship between the diameter of the SOV on brain MR images and the intracranial pressure (ICP). METHODS: We reviewed the medical records of neurologic inpatients who had undergone both MR imaging of the brain and lumbar puncture. MR imaging

Neurorehabilitation and neural repair, Jan 24, 2014

Obstacle crossing is a balance-challenging task and can cause falls in people with Parkinson'... more Obstacle crossing is a balance-challenging task and can cause falls in people with Parkinson's disease (PD). However, programs for people with PD that effectively target obstacle crossing and dynamic balance have not been established. To examine the effects of virtual reality-based exercise on obstacle crossing performance and dynamic balance in participants with PD. Thirty-six participants with a diagnosis of PD (Hoehn and Yahr score ranging 1 to 3) were randomly assigned to one of three groups. In the exercise groups, participants received virtual reality-based Wii Fit exercise (VRWii group) or traditional exercise (TE group) for 45 minutes, followed by 15 minutes of treadmill training in each session for a total of 12 sessions over 6 weeks. Participants in the control group received no structured exercise program. Primary outcomes included obstacle crossing performance (crossing velocity, stride length, and vertical toe obstacle clearance) and dynamic balance (maximal excursi...

The Journal of Headache and Pain, 2015

Background: Researches to date on the association between headache and weather have yielded incon... more Background: Researches to date on the association between headache and weather have yielded inconsistent results. Only a limited number of studies have examined the clinical significance of self-reported weather sensitivity. This study aimed to identify the difference in the association of headache with temperature between migraine patients with and without temperature sensitivity. Methods: 66 migraine patients (75.8 % female; mean age 43.3 ± 12.9 years) provided their 1-year headache diaries from 2007 to a headache clinic in Taipei, Taiwan. 34 patients (51.5 %) reported sensitivity to temperature change but 32 (48.5 %) did not. Time series of daily headache incidence was modeled and stratified by temperature sensitivity. Empirical mode decomposition was used to identify temporal weather patterns that were correlated to headache incidence, and regression analysis was used to examine the amount of variance in headache incidence that could be explained by temperature in different seasons. Results: Among all migraine patients, temperature change accounted for 16.5 % of variance in headache incidence in winter and 9.6 % in summer. In winter, the explained variance increased to 29.2 % among patients with temperature sensitivity, but was not significant among those without temperature sensitivity. Overall, temperature change explained 27.0 % of the variance of the mild headache incidence but only 4.8 % of the incidence of moderate to severe headache during winter. Conclusions: This diary-based study provides evidence to link the perception of temperature sensitivity and headache incidence in migraine patients. Those who reported temperature sensitivity are more likely to have headache increase during the winter, particular for mild headaches.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medica- tions c... more The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medica- tions currently used for acute migraine attacks in Taiwan according to the principles of evidence-based med- icine. We have assessed the quality of clinical trials, levels of evidence, and referred to other treatment guidelines proposed by Western countries and Japan. After several panel discussions, we merged opinions from

Cephalalgia : an international journal of headache, Jan 17, 2015

Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine... more Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine attacks, but shares other visual deficits in between attacks with migraine without aura (MO). Here, we seek to determine if abnormalities specific to interictal MA patients exist in functional brain connectivity of intrinsic cognitive networks. In particular, these networks are involved in top-down modulation of visual processing. Using resting-state functional magnetic resonance imaging, whole-brain functional connectivity maps were derived from seeds placed in the anterior insula and the middle frontal gyrus, key nodes of the salience and dorsal attention networks, respectively. Twenty-six interictal MA patients were compared with 26 matched MO patients and 26 healthy matched controls. The major findings were: connectivity between the anterior insula and occipital areas, including area V3A, was reduced in MA but not in MO. Connectivity changes between the anterior insula and occipital...

Journal of neurology, neurosurgery, and psychiatry, 2015

Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (... more Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH. Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed. Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-...