Institute of Brain Science

of Brain, Taiwan

Institute of Brain Science

of Brain, Taiwan

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Liang J.-F.,National Yang Ming University | Liang J.-F.,Taipei Veterans General Hospital | Wang S.-J.,National Yang Ming University | Wang S.-J.,Taipei Veterans General Hospital | Wang S.-J.,Institute of Brain Science
Cephalalgia | Year: 2014

Background: Hypnic headache (HH), first reported in 1988, is a rare sleep-related headache disorder. In 2013 a new diagnostic criteria was proposed for HH in the International Classification of Headache Disorders, the third version beta (ICHD-3β). Purpose: This review aimed to update the clinical characteristics, therapeutic options and clinical outcomes in patients with HH and also validate the new diagnostic criteria. Methods: Based on a literature search in the major medical databases, we analyzed all case reports or case series on HH that have been published since the first description by Raskin. Except for symptomatic patients, all reported patients were included regardless of which diagnostic criteria were adopted. Four studies that reported the field-testing results of the ICHD-2 criteria were selected to validate the new ICHD-3β criteria. Results: In total, 250 adult and five childhood patients are described in this review. The majority of patients were elderly and their ages of onset were typically more than 50 years old (92%). Approximately 7.7% of patients had some trigeminal autonomic features, which are not permitted in the ICHD-3β criteria. Compared with the ICHD-2 criteria, the diagnostic rate under the new criteria increased from 65% to 85% in recently reported cases. Randomized control trials both for acute and prophylactic treatment are lacking. Based on observational studies, the most effective acute treatment is caffeine and prophylactic medications in use are lithium, caffeine and indomethacin. Without treatment, the disease course is usually protracted but spontaneous remission did occur in 12 patients (4.8%). In those treated with prophylactic agents, no recurrence was noted in 43% of patients, even following withdrawal of medication. Conclusions: The new ICHD-3β criteria are more sensitive and exhaustive for HH than the ICHD-2 criteria. Prophylactic treatment provides better outcomes; however, randomized controlled studies for treatment are needed to further verify the efficacy of the different drugs. © International Headache Society 2014.


Lee Y.-J.,National Yang Ming University | Lee Y.-J.,Taipei Veterans General Hospital | Chen Y.-T.,Taipei City Hospital Heping Fuyou Branch | Chen Y.-T.,Taipei Veterans General Hospital | And 10 more authors.
Cephalalgia | Year: 2014

Background: Cluster headache (CH) is well known to show a seasonal predilection; however, the impact of temperature and other meteorological factors on cluster periods (or bouts) has not been established. Methods: This nationwide survey included 758 patients with episodic CH retrieved from the Taiwan National Health Insurance Research Database from 2005 to 2009. Corresponding meteorological recordings were obtained from the Central Weather Bureau. A case-crossover study design was used to investigate the association between cluster periods and meteorological factors. Results: A total of 2452 episodes of cluster periods were recorded. The cluster periods were most frequent in the autumn and least frequent in the winter. Seasonal changes from winter to spring and from autumn to winter also increased the frequency of cluster periods. The risk of cluster periods increased when there was a higher mean temperature on event days (odds ratio (OR), 1.014, 95% confidence interval (CI), 1.005-1.023, =0.003) or within seven to 56 days. Either an increase or a decrease in temperature (0.05°C/day) following a warm period (mean temperature≥26°C) was associated with the onset of cluster periods. In contrast, a greater increase in temperature (0.15°C/day) following a cold period (mean temperature<21°C) was needed to evoke cluster periods. No such associations were found following moderate periods (21°C≤mean temperature<26°C). Discussion: Our study shows that temperature is associated with precipitating or priming cluster periods. The influence depends on the temperature of the preceding periods. © International Headache Society 2014.


Liu H.-Y.,Institute of Brain Science | Liu H.-Y.,National Yang Ming University | Liu H.-Y.,Buddhist Tzu Chi General Hospital | Fuh J.-L.,National Yang Ming University | And 10 more authors.
Neurology | Year: 2015

Objectives: To identify the frequency, clinical effects, and suicide risk in comorbid fibromyalgia (FM) among patients with migraine. Methods: We surveyed patients with migraine who attended a headache clinic. All patients completed questionnaires containing demographics, headache profiles based on the International Classification of Headache Disorders, 2nd edition, FM questionnaires based on the modified 2010 American College of Rheumatology preliminary diagnostic criteria, Migraine Disability Assessment, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index. Suicide risk was evaluated by self-report of lifetime suicidal ideation and attempts. Results: Of the 1,318 recruited patients with migraine (aged 42.6 ± 12.7 years; female/male 4.5), 10.1% (aged 44.3 ± 12.6 years; female/male 7.9) had comorbidity of FM. Patients with migraine and comorbid FM had higher headache frequency and headache-related disability, poor sleep quality, and were more depressed/anxious than those with migraine only (p < 0.001). Suicidal ideation and attempts were reported in 27.3% and 6.9% of patients with migraine, respectively, and were higher in patients with comorbid FM than in those without (ideation: 58.3% vs 24%; attempt: 17.6% vs 5.7%; p < 0.001). In addition, comorbidity of FM was associated with a higher suicide risk in 3 different migraine subgroups, i.e., migraine without aura, migraine with aura, and chronic migraine. After controlling for covariates, comorbidity of FM remained as a predictor of suicidal ideation and attempts (odds ratio 2.61 and 1.99, respectively, p < 0.05) in patients with migraine. Conclusions: Comorbidity with FM is associated with a high suicide risk in patients with migraine. © 2015 American Academy of Neurology.


Lee Y.-J.,Neurological Institute | Lee Y.-J.,National Yang Ming University | Hu Y.-W.,Cancer Center | Hu Y.-W.,National Yang Ming University | And 7 more authors.
Neuroepidemiology | Year: 2013

Background: Previous studies suggested a decreased risk of cancer among patients with Alzheimer's disease (AD). There is still a lack of data on the specific types of cancer, the risk factors, and the impact of cholinesterase inhibitors on developing cancer in AD. Methods: We performed a nationwide population-based study of 6,960 patients with AD between 1997 and 2006 using Taiwan's National Health Insurance database. Patterns of cancer incidence in AD patients were compared with those of the general population using standardized incidence ratios (SIRs). Results: Patients with AD had a reduced risk of developing overall cancer [SIR = 0.88, 95% confidence interval (CI) = 0.80-0.97]. Specifically, patients with AD were protected from lung cancers (SIR = 0.75, 95% CI = 0.57-0.98), especially men (SIR = 0.61, 95% CI = 0.40-0.88). In subgroup analyses, women, patients aged 60-79 years, and those diagnosed as having AD for more than 1 year were more likely to be protected from cancers. Conclusions: Our study demonstrates a decreased incidence of overall cancers in patients with AD, a finding lower than but consistent with Western countries. Patients with AD had a significantly decreased risk of lung cancer. Further investigation of genetic evidence linking AD to cancer is warranted. Copyright © 2012 S. Karger AG, Basel.


Li C.-T.,Taipei Veterans General Hospital | Li C.-T.,National Yang Ming University | Tu P.-C.,Taipei Veterans General Hospital | Tu P.-C.,National Yang Ming University | And 14 more authors.
Bipolar Disorders | Year: 2015

Objectives: Bipolar I disorder (BD) is a highly heritable disorder characterized by mood swings between high-energy and low-energy states. Amygdala hyperactivity and cortical inhibitory hypoactivity [e.g., of the dorsolateral prefrontal cortex (dlPFC)] have been found in patients with BD, as evidenced by their abnormal resting-state functional connectivity (FC) and glucose utilization (GU). However, it has not been determined whether functional abnormalities of the dlPFC-amygdala circuit exist in unaffected, healthy siblings of the patients with BD (BDsib). Methods: Twenty euthymic patients with BD, 20 unaffected matching BDsib of the patient group, and 20 well-matched healthy control subjects were recruited. We investigated seed-based FC (seeds: dlPFC) with resting-state functional magnetic resonance imaging and GU in the regions of interest (e.g., dlPFC and amygdala) using 18F-fluorodeoxyglucose positron emission tomography. Results: The FC in the dlPFC (right)-amygdala circuit was statistically abnormal in patients with BD and BDsib, but only the patients with BD demonstrated hypoactive GU bilaterally in the dlPFC and hyperactive GU bilaterally in the amygdala. Facilitating differentiation between the BD groups, the altered FC between dlPFC (right) and amygdala (left) was even more prominent in the patients with BD (p < 0.05). Conclusions: There was a dysfunctional connection with intact GU in the dlPFC-amygdala circuit of the BDsib, which highlights the vulnerability in families with BD. Diminished top-down control from the bilateral dlPFC, which prevents adequate inhibition of limbic hyperactivity, might mediate the development of BD. © 2015 John Wiley & Sons A/S.


Ishii A.,Fukuoka University | Kanaumi T.,Fukuoka University | Sohda M.,Niigata University | Misumi Y.,Fukuoka University | And 11 more authors.
Epilepsy Research | Year: 2014

Mutations in GABRG2, which encodes the γ2 subunit of GABAA receptors, can cause both genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. Most GABRG2 truncating mutations associated with Dravet syndrome result in premature termination codons (PTCs) and are stably translated into mutant proteins with potential dominant-negative effects. This study involved search for mutations in candidate genes for Dravet syndrome, namely SCN1A, 2A, 1B, 2B, GABRA1, B2, and G2. A heterozygous nonsense mutation (c.118C>T, p.Q40X) in GABRG2 was identified in dizygotic twin girls with Dravet syndrome and their apparently healthy father. Electrophysiological studies with the reconstituted GABAA receptors in HEK cells showed reduced GABA-induced currents when mutated γ2 DNA was cotransfected with wild-type α1 and β2 subunits. In this case, immunohistochemistry using antibodies to the α1 and γ2 subunits of GABAA receptor showed granular staining in the soma. In addition, microinjection of mutated γ2 subunit cDNA into HEK cells severely inhibited intracellular trafficking of GABAA receptor subunits α1 and β2, and retention of these proteins in the endoplasmic reticulum. The mutated γ2 subunit-expressing neurons also showed impaired axonal transport of the α1 and β2 subunits. Our findings suggested that different phenotypes of epilepsy, e.g., GEFS+ and Dravet syndrome (which share similar abnormalities in causative genes) are likely due to impaired axonal transport associated with the dominant-negative effects of GABRG2. © 2014 Elsevier B.V.


Stetler R.A.,Institute of Brain science | Stetler R.A.,Geriatric Research | Stetler R.A.,University of Pittsburgh | Leak R.K.,Duquesne University | And 9 more authors.
Journal of Neurochemistry | Year: 2012

Although alterations in mitochondrial dynamics are associated with cellular responses to injury, the functional role of these dynamic changes in ischemic neurons is underexplored. One of these dynamic responses to injury includes mitochondrial biogenesis. Various sublethal pre-conditioning stimuli that induce an ischemic-tolerant state [e.g., lipopolysaccharide (LPS)] may also induce mitochondrial biogenesis. Using neuron-enriched cultures, we found that sublethal LPS pre-conditioning induced both ischemic tolerance and markers of mitochondrial biogenesis with overlapping dose-response temporal kinetics. Sublethal LPS transiently increased the expression of critical components of the mitochondrial transcriptional machinery, including nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), as well as mtDNA copy number, mitochondrial protein levels, and markers of functional mitochondria, such as increased cellular ATP content, citrate synthase activity, and maximal respiration capacity. Importantly, knockdown of TFAM abrogated both the induction of mitochondrial biogenesis and the neuroprotective pre-conditioning effects of LPS. Several signaling pathways coordinated these events. AMPK inhibition suppressed NRF1 and TFAM expression by LPS, whereas PI3K/Akt signaling was necessary for the nuclear translocation of NRF1 and subsequent induction of TFAM. This is the first demonstration that LPS pre-conditioning initiates multiple signaling pathways leading to mitochondrial biogenesis in neurons and that these dynamic changes contribute to ischemic tolerance. © 2012 International Society for Neurochemistry.


Liu J.-Y.,Fudan University | Ding J.,Fudan University | Lin D.,Fudan University | He Y.-F.,Fudan University | And 8 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To evaluate regional brain iron deposition in minimal hepatic encephalopathy (MHE) patients using T2*-weighted gradient-echo imaging and to explore the relationship between T2* MR changes and cognitive performance. Materials and Methods: Forty hepatitis-B virus (HBV)-related cirrhotic patients and 22 age-, sex-, and education-matched healthy controls were included in this study. Of the patients, twenty eight patients were diagnosed with MHE. All subjects were administered Number Connection Test-A (NCT-A), Letter Digit Substitution Test (LDST), Rey-Osterrieth Complex Figure Test (RCFT), and the Mini-Mental State Examination (MMSE). T2*-weighted gradient-echo images were acquired using 3 Tesla MRI. Phase values (putative iron levels) in the frontal-basal ganglia-thalamocortical circuits were measured. Spearman correlation and multiple linear regression analysis were performed. Results: MHE patients exhibited significantly prolonged NCT-A time and decreased LDST, RCFT immediate and delayed recall scores. Significant decreases of phase values in the bilateral putamen were detected in MHE patients compared to without MHE patients and controls. Multiple linear regression analysis confirmed significant correlations between the phase values in the putamen and right frontal white matter and cognitive performances by MHE patients. Conclusion: Decreased phase values in the frontal cortical-basal ganglial circuits independently contribute to cognitive impairments in MHE patients. J. Magn. Reson. Imaging 2013;37:179-186. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.


Mao L.-Y.,Fudan University | Ding J.,Fudan University | Peng W.-F.,Fudan University | Ma Y.,Fudan University | And 4 more authors.
Epilepsia | Year: 2013

Interleukin 17A (IL-17A) is implicated in the pathogenesis of several neuroimmunologic diseases. We aimed to evaluate the relationship between IL-17A and seizure severity in patients with epilepsy. Seventy patients with probable symptomatic epilepsy and 68 healthy controls were included. Interictal serum IL-17A and related cytokine (IL-23, IL-6, IL-1β, interferon gamma (IFN-γ), and IL-10) levels were measured. The relationship between seizure severity and cytokine concentrations was assessed by Spearman correlation and multivariate linear regression test. IL-17A levels in the cerebrospinal fluid (CSF) were tested in 30 additional patients with epilepsy, either in the postictal or interictal period and 15 patients with idiopathic inflammatory demyelinating diseases (IIDDs). Interictal serum IL-17A levels were significantly elevated in patients with epilepsy compared to controls. IL-6, IFN-γ, and IL-1β levels were also markedly elevated. Spearman correlation analysis revealed positive correlation between IL-17A, IL-6 levels and Veterans Administration Seizures Frequency and Severity Rating Scale score(VA score); IFN-γ, IL-10 levels, and National Hospital Seizure Severity Scale (NHS3) score. In addition, IL-17A levels correlated significantly with seizure frequency. Multivariate linear regression test showed that only IL-17A levels were independently positively correlated with VA scores (B = 0.288, p = 0.027). Postictal IL-17A levels in the CSF were significantly elevated compared to interictal patients and patients with IIDDs. Our results suggest that interictal IL-17A levels correlated highly with seizure severity. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.


Chu M.,Institute of Brain Science | Hu X.,Geriatric Research | Hu X.,University of Pittsburgh | Lu S.,Institute of Brain Science | And 9 more authors.
Frontiers in Bioscience - Elite | Year: 2012

Cerebral ischemia triggers regeneration of neural stem/progenitor cells (NSCs/NPCs), which are associated with neovascularization and white matter repair in the brain. This study analyzed the dynamics of neurogenesis, neovascularization, and white matter injury/repair after middle cerebral artery occlusion (MCAO) and elucidated their temporal association. Mice were subjected to MCAO for 60 minutes and sacrificed up to 28 days after reperfusion. Neurogenesis and angiogenesis, as measured by double staining of 5-bromo-2-deoxyuridine (BrdU) with DCX or tomato lectin, respectively, were substantially activated soon after ischemia and persisted for 4 weeks. Despite the moderate recovery of functional vessels in infarct margin from 7 days post-ischemia, a significant decrease in vascular density remained over time. Clusters of immature neurons localized proximal to angiogenic blood vessels beginning 14 days after ischemia, suggesting interplay between neurogenesis and revascularization. Progenitors of oligodendrocytes (NG2+) constitutively presented in the normal brain and proliferated soon after ischemia. However, axon damage and the loss of white matter integrity after ischemic stroke were almost irreversible, as revealed by sustained decreases of myelin basic protein (MBP) and neurofilament-200 expression.

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