Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Low pulse pressure and high serum complement C1q are risk factors for hemodialysis headache: A case-control study.

BACKGROUND AND OBJECTIVE: Hemodialysis headache (HDH) is a common complication of dialysis that negatively affects the patient's quality of life. The etiology and triggering factors of HDH are not fully understood. This study aims to assess the prevalence and characteristics of HDH among patients undergoing hemodialysis across multiple centers in China. Furthermore, we conducted a case-control study at one hospital to identify risk factors associated with HDH. METHODS: The study consisted of two phases including a cross-sectional observational study and a case-control study. Participants underwent neurological examinations and interviews. Demographic and medical information were collected from both medical records and patient files. Serum creatinine, uric acid, urea, estimated glomerular filtration rate (eGFR), plasma osmolarity, glucose, C1q, and a variety of electrolytes including potassium, sodium, chloride, calcium, magnesium, and phosphorus were measured before and after dialysis. Blood pressure variables including systolic blood pressure, diastolic blood pressure, pulse pressure (PP), and heart rate were monitored hourly. Serum levels of inflammatory factors, including tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-4, IL-6, and IL-10 were quantified using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of HDH was 37.7% (183/485). HDH was characterized by a bilateral tightening headache of moderate intensity and duration of <2 h, occurring in different locations. The case-control study included 50 patients with HDH and 84 control patients, pre-dialysis PP was found to be lower in the HDH group than in the control group (mean ± standard deviation 51.5 ± 18.2 vs. 67.9 ± 14.9, p = 0.027). Furthermore, the pre-dialysis serum complement C1q level was significantly higher for the HDH group than the control group (median and interquartile range 201.5 [179.0-231.5] vs. 189.0 [168.9-209.0], p = 0.021). Pre-dialysis PP was associated with 5.1% decreased odds of HDH (odds ratio [OR] = 0.96; 95% confidence interval [CI], 0.93-0.99, p = 0.026), body weight was associated with a 5.4% decreased risk of HDH (OR = 0.95; 95% CI, 0.91-0.99, p = 0.013), and pre-dialysis C1q levels increased the odds of HDH by 1.9% (OR = 1.02; 95% CI, 1.01-1.03, p = 0.005). CONCLUSION: Low PP, low body weight, and high blood complement C1q may be potential risk factors associated with HDH.

Executive function impairment is associated with low serum vitamin D levels in children with epilepsy.

PURPOSE: Executive function (EF) impairment and vitamin D deficiency are common clinical features among children with epilepsy (CWE). Recently, vitamin D has become a potential modification factor that affects cognitive status in individuals with neurological disorders. In this study, we investigated the association between EF status and vitamin D levels in patients with CWE. METHODS: In total, 79 CWE patients and 39 healthy controls (HCs) were recruited in this study. Each participant's EF was assessed using the Behavior Rating Inventory of Executive Function-Parent form (Brief-P), and the serum level of 25-OH vitamin D was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Compared with those in the HC group, the CWE group had higher T scores of Brief-P scale, including global executive composite (GEC) (51.01(45.12, 60.69) vs. 44.08(39.24, 49.96), p＜0.001), behavioral regulation index (BRI) (51.29(45.67, 59.13) vs. 45.67(40.06, 51.29), p＜0.001), metacognition index (MI) (51.83(46.77, 59.43) vs. 46.13(40.44, 51.83), p＜0.001), and lower serum vitamin D (14.85(10.24,23.2) vs. 22.5(16.91,30), p＜0.001) levels. After adjustment for covariates, multivariate linear regression models suggested that for every 1 ng/ml increase in vitamin D, the GEC, BRI, and MI would decrease by 0.52 (Coeff = -0.48; 95 % CI = -0.69, -0.26; p = 0.000), 0.45 (Coeff = -0.45; 95 % CI = -0.69, -0.20; p = 0.000), and 0.47 (Coeff = -0.45; 95 % CI = -0.67, -0.22; p = 0.000), respectively. CONCLUSION: There may be an association between decreased vitamin D levels and EF impairment in CWE. Future research should consider longitudinal variations in EF related to improving vitamin D deficiency.

Poor healthy lifestyle and life's essential 8 are associated with higher risk of new-onset migraine: a prospective cohort study.

BACKGROUND: Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life's Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life's essential 8 scores, and migraine. METHODS: 332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence. RESULTS: During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively. CONCLUSION: Our study provides evidence that poor Healthy lifestyle and Life's Essential 8 are associated with higher risk of new-onset migraine.

Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide widely distributed in the trigeminovascular system (TVS) and higher brain regions. At present, the underlying mechanism of PACAP/PACAP type1 (PAC1) receptor in migraine generation remains unclear. METHODS: The rat model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and hot plate tests were used to measure the mechanical and thermal thresholds. The expression levels of c-Fos, calcitonin gene-related peptide (CGRP), PACAP, PAC1, protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (ERK) were assessed by western blotting or immunofluorescence staining. The internalization of PAC1 receptor was visualized by fluorescence microscope and laser scanning confocal microscope. RESULTS: The results showed that c-Fos and CGRP expression significantly increased after repeated administrations of NTG or PACAP. Pitstop2 notably improved hyperalgesia in CM rats, while PACAP6-38 offered no benefit. In addition, PACAP-induced PAC1 receptor internalization, PKA and ERK pathways activation were blocked by Pitstop2 instead of PACAP6-38. CONCLUSIONS: Our results demonstrate that inhibition of PAC1 receptor internalization could effectively improve allodynia in CM rats by restraining ERK signaling pathway activation in a chronic migraine rat model. Modulation of receptor internalization may be a novel perspective to explore specific mechanisms of PACAP signaling activation in the trigeminal vascular system.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH. METHODS: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint. RESULTS: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints. CONCLUSION: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.

OBJECTIVE: To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine. BACKGROUND: Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. METHODS: A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)-like rats were quantified and the changes in Treg/Th17-related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2-(1'-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and AHR antagonist CH-223191 on pain behavior, c-Fos, calcitonin gene-related peptide (CGRP), AHR, and Treg/Th17-related factor expression in CM-like rats. RESULTS: Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c-Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor-related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta-1 was decreased, while that of interleukin (IL)-10 and IL-22 was increased in the TNC. The AHR agonist ITE alleviated migraine-like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17-related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH-223191 did not alleviate migraine-like pain behaviors in rats; and even exacerbated them. CONCLUSIONS: The AHR participates in the development of CM by regulating Treg/Th17-related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment.

PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.

AIMS: Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model. METHODS: Sprague-Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons. RESULTS: The results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38. CONCLUSIONS: Our results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.

SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1α positive feedback loop.

Migraine is the second highest cause of disability worldwide, bringing a huge socioeconomic burden. Improving mitochondrial function has promise as an effective treatment strategy for migraine. Szeto-Schiller peptide (SS-31) is a new mitochondria-targeted tetrapeptide molecule that has been shown to suppress the progression of diseases by restoring mitochondrial function, including renal disease, cardiac disease, and neurodegenerative disease. However, whether SS-31 has a therapeutic effect on migraine remains unclear. The aim of this study is to clarify the treatment of SS-31 for headache and its potential mechanisms. Here we used a mouse model induced by repeated dural infusion of inflammatory soup (IS), and examined roles of Sirt3/Pgc-1α positive feedback loop in headache pathogenesis and mitochondrial function. Our results showed that repeated IS infusion impaired mitochondrial function, mitochondrial ultrastructure and mitochondrial homeostasis in the trigeminal nucleus caudalis (TNC). These IS-induced damages in TNC were reversed by SS-31. In addition, IS-induced nociceptive responses were simultaneously alleviated. The effects of SS-31 on mitochondrial function and mitochondrial homeostasis (mainly mitochondrial biogenesis) were attenuated partially by the inhibitor of Sirt3/Pgc-1α. Overexpression of Sirt3/Pgc-1α increased the protein level of each other. These results indicated that SS-31 alleviated nociceptive responses and restored mitochondrial function in an IS-induced headache mouse model via Sirt3/Pgc-1α positive feedback loop. SS-31 has the potential to be an effective drug candidate for headache treatment.

Comparison of the effects of different doses of Glucocorticoids on distinct subtypes of Guillain-Barré syndrome in Southern China.

BACKGROUND: The effect of Glucocorticoids (GCs) on the treatment of Guillain-Barré syndrome (GBS) has been controversial. There is no information on whether specific subtypes of GBS respond differently to GCs. In this setting, we aimed to discuss whether GCs treating yield different effects in the distinct subtypes (acute inflammatory demyelinating polyneuropathy, AIDP; acute motor axonal neuropathy, AMAN). And further, we analyzed the impact of different doses on the outcome. METHODS: Medical records of 448 patients with a diagnosis of classic GBS admitted to 31 tertiary hospitals, located in 14 provinces of Southern China, from 1 January 2013 to 30 September 2016, were retrospectively collected. And 251 patients treated with GCs alone (AIDP=189, AMAN=62) were reviewed and analyzed. RESULTS: After GCs treatment, the Hughes score of AIDP patients was significantly lower than that of AMAN patients at discharge (P=0.005) and 3 months after onset (P<0.001). Further analysis revealed that among AIDP patients, the high-dose group had significantly shorter hospital stay (P=0.023), lower Hughes score at nadir (P<0.001), at discharge (P=0.005), and 3 months after onset (P<0.001), compared with the low-dose group. However, for AMAN patients, the outcome difference between groups was nonsignificant. CONCLUSION: Our data suggest that the high doses of GCs may result, at least in part, from the side of the duration of hospital stay and short-term outcome, favorable outcomes in AIDP patients. Therefore, we cannot completely deny the priority of GCs in the treatment of GBS, because the effect of different doses of GCs varies in treating different subtypes. More studies are needed in the future to further validate this issue. TRIAL REGISTRATION: ChiCTR-RRC-17014152 . Registered 26 December 2017- Retrospectively registered.

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats.

BACKGROUND: The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine. METHODS: Model rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation. RESULTS: Microglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia. CONCLUSIONS: Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.

Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1ß and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine.

Overall trend towards headache remission during the COVID-19 pandemic among Chinese patients with pre-existing headache highlights the role of family support.

BACKGROUND: The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China. METHODS: A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire. RESULTS: Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P<0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P<0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P<0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches. CONCLUSIONS: Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches.

Guillain-Barré syndrome triggered by surgery in a Chinese population: a multicenter retrospective study.

BACKGROUND: Surgery is a potential trigger of Guillain-Barré syndrome (GBS), a disorder which leads to an autoimmune-mediated attack of peripheral nerves. The present study was designed to explore clinical features of post-surgical GBS compared with those of general GBS in order to provide better clinical advice to patients undergoing surgery. METHODS: The medical records of GBS patients who were seen at 31 tertiary hospitals in southern China between January 1, 2013 and September 30, 2016 were retrospectively analyzed. Post-surgical GBS was defined as symptoms of GBS within 6 weeks after surgery. Clinical features of post-surgical GBS are described and are compared with general GBS. RESULTS: Among the 1001 GBS patient cases examined in this study, 45 (4.5%) patient cases exhibited symptoms of GBS within 6 weeks of undergoing surgery. Within this group, 36 (80.0%) patients developed initial symptoms of limb weakness. The average interval between surgery and symptom onset was 13.31 days. The most common type of surgery which triggered GBS was orthopedic surgery, followed by neurological surgery. Compared to general GBS, post-surgical GBS was characterized by a higher proportion of severe patients (Hughes functional grading scale (HFGS) score ≥ 3) upon admission and at nadir, higher HFGS scores at discharge, and longer hospital stays. Post-surgical GBS patients also had a significantly higher frequency of the acute motor axonal neuropathy subtype (37.9 vs. 14.2, respectively; P = 0.001). CONCLUSION: Surgery is probably a potential trigger factor for GBS, especially orthopedic surgery. Infections secondary to surgery may play a role. The possibility of preceding (post-operative) infections was not excluded in this study. Clinical presentation of post-surgical GBS is characterized by a more severe course and poorer prognosis, and should be closely monitored. TRIAL REGISTRATION: chicTR-RRc-17,014,152 .

Missense mutations in LAMA2 causing a new phenotype of mild cognitive impairment, proximal myopathy, seizure, and severe leukoencephalopathy: A case report and protein analysis.

Congenital muscular dystrophy with laminin-α2 deficiency, also known as MDC1A, displays an extensive phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counseling. Here we report one individual from a family presenting with clinical features including seizure attack, slight weakness of proximal leg muscles, and mild cognitive impairment with increased small angular fibers, decreased expression of α-DG and ß-DG, normal expression of laminin-α2, and severe white matter changes. Targeted next-generation sequencing (NGS) revealed two homozygous missense mutations, c.2881G>A (p.Ala961Thr) and c.4406G>A (p.Cys1469Tyr), in LAMA2 in the affected member of the family. Together, these results demonstrate a role for c.2881G>A and c.4406G>A mutations in LAMA2 and show that these two mutations, especially c.4406G>A, may cause mild cognitive impairment, slight motor retardation, seizures, and severe leukoencephalopathy, which extends the clinical spectrum associated with LAMA2 mutations.

Clinical Features and the Validation of the Brighton Criteria in Guillain-Barré Syndrome: Retrospective Analysis of 72 Hospitalized Patients in Three Years.

OBJECTIVE: To analyze the clinical phenotypes and features of Guillain-Barré syndrome (GBS) in our hospital and explore the diagnostic value of the Brighton criteria. METHODS: We retrospectively analyzed the clinical data of GBS patients hospitalized in our hospital from January 1, 2013, to September 30, 2016. The patients were affirmatively graded according to the Brighton criteria (highest: level 1, lowest: level 4). RESULT: (1) We enrolled 72 patients with GBS, including 7 with cranial nerve variants, 4 with Miler-Fisher syndrome, and 61 with classic GBS that mainly presented as limb weakness. (2) A total of 56.94% of the included patients had preceding events, of which respiratory tract infections accounted for 63.41%; there was a significant difference in the incidence of GBS across the spring, summer, autumn, and winter. Weakness was the first symptom in 75% of patients, all patients reached peaked within 4 weeks, and 94.44% of the patients presented with decreased or absent deep tendon reflexes. Among the patients who completed a lumbar puncture cerebrospinal fluid (CSF) examination, 73.24% showed proteins dissociated from CSF cells. Demyelinating GBS was found in 54%, and axonal GBS was found in 22% of the patients who completed an electrophysiological examination. All patients with classic GBS were graded according to the Brighton diagnostic criteria as level 1 (60.66%, 37/61), level 2 (34.42%, 21/61), level 3 (4.92%, 3/61), or level 4 (0%). CONCLUSION: In our hospital, the clinical features of patients with GBS were similar to those described in previous studies, but demyelinating GBS was the most important subtype. Most preceding events were upper respiratory tract infections. The Brighton criteria were highly sensitive, and perfect clinical data improved diagnostic grading. In areas where medical resources are relatively scarce, a detailed medical history and physical examination can help improve diagnostic accuracy.

Eosinophilic fasciitis associated with myositis: Report of four cases and review of the literature.

Eosinophilic fasciitis is a rare scleroderma-like syndrome with an unknown aetiology. The characteristics of this disorder include lymphoplasmacytic inflammation involving the subcutaneous fat septa and fascia. Eosinophilic myositis is diagnosed when inflammation extends into the muscles. Here, we describe four patients who developed eosinophilic fasciitis, three of whom developed eosinophilic fasciitis with myositis. Fascial and muscle biopsies were used to confirm the diagnoses. All the patients presented with musculoskeletal symptoms; their electromyographic examinations showed myogenic lesions [short-duration, low-amplitude and polyphasic motor unit action potentials (MUPs), so-called myopathic changes, frequently with abnormal spontaneous activity], in contrast with findings from other reports.

High signal-intensity abnormalities in susceptibility-weighted imaging for primary intracerebral hemorrhage.

Purpose: To identify the regularity of signal evolution of intracerebral hemorrhage on susceptibility-weighted imaging (SWI) at different stages compared with T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). Methods: We retrospectively evaluated a series of 365 patients who underwent T1WI, T2WI, and SWI examination simultaneously or sequentially in our hospital from January 2015 to May 2017. Two neuroradiologists assessed the images and discrepancies between their interpretations were resolved by consensus. Statistical analysis was performed using Chi-squared and Kappa tests. Results: Of the 365 patients on SWI sequence, 94 were enrolled. SWI detected the cases at different stages; T1WI detected 89 cases and T2WI detected 91 cases. The signal intensity of intracerebral hemorrhage on SWI was significantly associated with T1WI imaging and T2WI (χ2 = 4.651; p < 0.05; χ2 = 26.396; p < 0.01, respectively), especially at the late subacute stage. There was moderate consistency between the signal intensity of intracerebral hemorrhage on T2WI and SWI (Kappa coefficient = 0.530). Conclusion: Intracerebral hemorrhage has a varied appearance on SWI, and the evolution of signal of intracerebral hemorrhage on SWI sequence is influenced by T1WI and T2WI. Hematoma detection should be closely combined with clinical manifestation.

Increased Asics Expression via the Camkii-CREB Pathway in a Novel Mouse Model of Trigeminal Pain.

BACKGROUND/AIMS: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. METHODS: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. RESULTS: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP) in the periaqueductal grey matter. Interestingly, the acid-induced trigeminal pain behaviour was inhibited by amiloride, an antagonist of acid-sensing ion channels (ASICs), but not by AMG-9810, an inhibitor of transient receptor potential cation channel V1(TRPV1). In addition, the relative mRNA and protein expression levels of ASIC1a and ASIC3 were increased in the acid-induced trigeminal nociceptive pathways. Furthermore, blocking CaMKII with KN-93 significantly reduced the acid-induced trigeminal pain behaviour and c-FOS gene expression. CONCLUSION: The data suggested that chronic intermittent administration of an acidic solution to mice resulted in trigeminal hypersensitivity and that dural acid-induced trigeminal pain behaviour in mice may mechanistically mimic migraine. The observations here identify an entirely novel treatment strategy for migraine.

Guillain-Barré syndrome in southern China: retrospective analysis of hospitalised patients from 14 provinces in the area south of the Huaihe River.

OBJECTIVES: The clinical and epidemiological profiles of Guillain-Barré syndrome (GBS) in southern China have yet to be fully recognised. We aimed to investigate the subtypes of GBS in southern China, compare the clinical features of demyelinating form with that of axonal form and test whether preceding infections and age have influence on the clinical phenotype, disease course and severity of GBS. METHODS: Medical records of patients with a diagnosis of GBS admitted to 31 tertiary hospitals, located in 14 provinces in southern China, from 1 January 2013 to 30 September 2016, were collected and retrospectively reviewed. RESULTS: Finally. 1056 patients, including 887 classic GBS and 169 variants, were enrolled. The 661 classic patients with available electromyographic data were grouped as having acute inflammatory demyelinating polyneuropathy (AIDP, 49.0%), acute motor axonal neuropathy (AMAN, 18.8%), inexcitable (0.9%) and equivocal (31.3%). In contrast to AIDP, patients with AMAN were characterised by earlier nadir (P=0.000), higher Hughes score at nadir (P=0.003) and at discharge (P=0.000). Preceding upper respiratory infections were identified in 369 (34.9%) patients, who were more inclined to develop AIDP (P=0.000) and Miller-Fisher syndrome (P=0.027), whereas gastrointestinal infection were found in 89 (8.4%) patients, who were more prone to develop AMAN (P=0.000), with more severe illness (P=0.001) and longer hospital stay (P=0.009). Children (≤15 years) and the elderly (≥56 years) were more severe at nadir, the elderly had the longest hospital stay (P=0.023). CONCLUSION: AIDP is the predominant form in southern China, which is different from data of northern China. The different subtypes, preceding infection and age of onset can partially determine the disease progression, severity and short-term recovery speed of GBS. CLINICAL TRIAL REGISTRATION: ChiCTR-RRC-17014152.