Dopaminergic Projections from the Hypothalamic A11 Nucleus to the Spinal Trigeminal Nucleus Are Involved in Bidirectional Migraine Modulation.

Clinical imaging studies have revealed that the hypothalamus is activated in migraine patients prior to the onset of and during headache and have also shown that the hypothalamus has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system of the hypothalamus plays an important role, and the dopamine-rich A11 nucleus may play an important role in migraine pathogenesis. We used intraperitoneal injections of glyceryl trinitrate to establish a model of acute migraine attack and chronicity in mice, which was verified by photophobia experiments and von Frey experiments. We explored the A11 nucleus and its downstream pathway using immunohistochemical staining and neuronal tracing techniques. During acute migraine attack and chronification, c-fos expression in GABAergic neurons in the A11 nucleus was significantly increased, and inhibition of DA neurons was achieved by binding to GABA A-type receptors on the surface of dopaminergic neurons in the A11 nucleus. However, the expression of tyrosine hydroxylase and glutamic acid decarboxylase proteins in the A11 nucleus of the hypothalamus did not change significantly. Specific destruction of dopaminergic neurons in the A11 nucleus of mice resulted in severe nociceptive sensitization and photophobic behavior. The expression levels of the D1 dopamine receptor and D2 dopamine receptor in the caudal part of the spinal trigeminal nucleus candalis of the chronic migraine model were increased. Skin nociceptive sensitization of mice was slowed by activation of the D2 dopamine receptor in SP5C, and activation of the D1 dopamine receptor reversed this behavioral change. GABAergic neurons in the A11 nucleus were activated and exerted postsynaptic inhibitory effects, which led to a decrease in the amount of DA secreted by the A11 nucleus in the spinal trigeminal nucleus candalis. The reduced DA bound preferentially to the D2 dopamine receptor, thus exerting a defensive effect against headache.

Proteomics profiling reveals mitochondrial damage in the thalamus in a mouse model of chronic migraine.

BACKGROUND: Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis for the pathogenesis of migraine, hence we depicted the proteomics profiling of key regions in this system, then focusing on protein alterations related to mitochondrial function. The aim of this study is to illustrate the role of mitochondria in migraine. METHODS: A mouse model of chronic migraine (CM) was established by repeated nitroglycerin (NTG) stimulation and evaluated by von-Frey filaments, a hot plate and a light-dark box. Differentially expressed proteins (DEPs) in some subcortical brain regions of the trigeminovascular system were screened through liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyse the specificity of key signaling pathways in different brain regions. And then mitochondrial function, structure and dynamics were determined by qPCR, ELISA, and transmission electron microscope (TEM). Finally, the effect of mitochondrial intervention-Urolithin A (UA) on CM was investigated. RESULTS: Repeated NTG injection triggered photophobia, periorbital and hind paw allodynia in mice. The proteomics profiling of CM model showed that 529, 109, 163, 152 and 419 DEPs were identified in the thalamus, hypothalamus, periaqueductal grey (PAG), trigeminal ganglion (TG) and trigeminocervical complex (TCC), respectively. The most significant changes in the brain region-specific pathways pointed to thalamic mitochondrial impairment. NTG induced mitochondrial structural disruption, dysfunction and homeostatic dysregulation, which could be partially attenuated by UA intervention. CONCLUSION: Our findings highlight the involvement of mitochondrial damage in the thalamus in central sensitization of CM, which provides evidence of possible metabolic mechanisms in migraine pathophysiology.

Non-Pharmacological Treatment for Chronic Migraine.

PURPOSE OF REVIEW: Chronic migraine (CM) affects a large proportion of the population and is a significant source of disability and lost productivity. Numerous non-pharmacological approaches have been attempted during the past decades. This review discusses the most recent and evidence-based advances in acute and preventive non-pharmacological therapeutic approaches for CM, offering alternatives to drug treatment. RECENT FINDINGS: A growing number of non-pharmacological treatment options, including non-invasive or invasive neuromodulation, acupuncture, psychotherapy, and physiotherapy, have shown promising efficacy in CM. There is strong evidence for the effectiveness of non-invasive neuromodulation such as transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (TENS) in CM, but less evidence for approaches such as invasive neuromodulation, physical therapy, or dietary approaches. Acupuncture for migraine remains controversial, with the main point of contention still being the placebo effect. Non-pharmacological approaches can be offered as a reliable alternative for patients with CM, and more research is being done to evaluate the efficacy of non-invasive neuromodulation with different parameters and the combination of different treatments in CM.

Abnormal Thalamo-Cortical Interactions in Overlapping Communities of Migraine: An Edge Functional Connectivity Study.

OBJECTIVE: Migraine has been demonstrated to exhibit abnormal functional connectivity of large-scale brain networks, which is closely associated with its pathophysiology and has not yet been explored by edge functional connectivity. We used an edge-centric approach combined with motif analysis to evaluate higher-order communication patterns of brain networks in migraine. METHODS: We investigated edge-centric metrics in 108 interictal migraine patients and 71 healthy controls. We parcellated the brain into networks using independent component analysis. We applied edge graph construction, k-means clustering, community overlap detection, graph-theory-based evaluations, and clinical correlation analysis. We conducted motif analysis to explore the interactions among regions, and a classification model to test the specificity of edge-centric results. RESULTS: The normalized entropy of lateral thalamus was significantly increased in migraine, which was positively correlated with the baseline headache duration, and negatively correlated with headache duration reduction following preventive medications at 3-month follow-up. Network-wise entropy of the sensorimotor network was significantly elevated in migraine. The community similarity between lateral thalamus and postcentral gyrus was enhanced in migraine. Migraine patients showed overrepresented L-shape and diverse motifs, and underrepresented forked motifs with lateral thalamus serving as the reference node. Furthermore, migraine patients presented with overrepresented L-shape triads, where the postcentral gyrus shared different edges with the lateral thalamus. The classification model showed that entropy of the lateral thalamus had the highest discriminative power, with an area under the curve of 0.86. INTERPRETATION: Our findings indicated an abnormal higher-order thalamo-cortical communication pattern in migraine patients. The thalamo-cortical-somatosensory disturbance of concerted working may potentially lead to aberrant information flow and deficit pain processing of migraine. ANN NEUROL 2023;94:1168-1181.

Dietary zinc intake and migraine in adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004.

OBJECTIVE: The study examined the relationship between dietary zinc intake and migraine. BACKGROUND: Neuroinflammatory and oxidative stress are involved in the pathogenesis of migraine. Little is known about the effects of zinc, an anti-inflammatory and antioxidant trace element, on migraine. METHODS: The US National Health and Nutrition Examination Survey data from 1999 to 2004 were analyzed for this cross-sectional study. Participants who had severe headache or migraine were classified as having migraine. Dietary zinc intake was evaluated using the 24 h dietary recall system. RESULTS: A total of 11,088 participants were included, of whom, 20.2% (2236/11,088) reported having migraine disease. Compared to the lowest dietary zinc intake quintile (Q1, ≤5.9 mg/day), the adjusted odds ratios for migraine in Q2 (6.0-8.4 mg/day), Q3 (8.5-11.2 mg/day), Q4 (11.3-15.7 mg/day), and Q5 (≥15.8 mg/day) were 0.73 (95% confidence interval [CI]: 0.61-0.88, p = 0.004), 0.71 (95% CI: 0.56-0.91, p = 0.013), 0.71 (95% CI: 0.57-0.90, p = 0.008), and 0.70 (95% CI: 0.52-0.94, p = 0.029), respectively. Sensitivity analysis of zinc supplementation survey participants also showed an association between dietary zinc intake and migraine. Compared to the lowest total zinc intake quintile (Q1: 0.5-9.6 mg/day), the adjusted odds ratios for migraine in Q3 (19.3-24.3 mg/day) and Q4 (24.4-32.5 mg/day) were 0.62 (95% CI: 0.46-0.83, p = 0.019) and 0.67 (95% CI: 0.49-0.91, p = 0.045), respectively. CONCLUSIONS: Our findings indicate an inverse association between dietary zinc intake and migraine in adult Americans.

Effects on neuromodulation, acupuncture, and aerobic exercises on migraine and tension-type headache outcomes: A systematic review and meta-analysis.

BACKGROUND: Headache disorders are common diseases that cause a social burden. This systematic review and meta-analysis aimed to evaluate the effects of various non-pharmacological treatments to address or prevent acute headaches, including neuromodulation, acupuncture, and aerobic exercises in patients with episodic migraine and tension-type headache (TTH). METHODS: We performed a systematic search of the electronic databases PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WANFANG MEDICINE ONLINE, and Chinese Medical Journal database using Stata/SE 14.0 to obtain weighted mean differences (WMDs). The outcomes included monthly headache days, headache intensity, headache duration, days per month of acute medication use, and the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Of 872 identified articles, 27 were included in the meta-analysis. Neuromodulation was associated with reduced headache days (WMD: -1.274, 95% CI [-1.914, -0.634], P < .001), duration (WMD: -2.2, 95% CI [-3.32, -0.107], P < .001) and medication consumption (WMD: -1.808, 95% CI [-2.546, -1.071], P < .001) in cases of migraine. Acupuncture was associated with the alleviation of headache days (WMD: -0.677, 95% CI [-0.932, -0.422], P < .001) and intensity (WMD: -0.893, 95% CI [-1.573, -0.212], P = .01) in cases of migraine and acute medication use (WMD: -3.29, 95% CI [-4.86, -1.72], P < .001) in cases of TTH. Aerobic exercise was associated with reduced headache duration (WMD: -5.1, 95% CI [-8.97, -1.22], P = .01) in cases of TTH. The risk of bias for included articles was moderate. CONCLUSIONS: There is low- and moderate-quality evidence that neuromodulation, acupuncture, and aerobic exercises are associated with attenuated headache symptoms in patients with episodic migraine or TTH. However, high-quality studies are needed to draw more detailed conclusions.

Primary Central Nervous System Lymphoma Mimicking Wernicke's Encephalopathy.

Primary central nervous system lymphoma (PCNSL) is a rare disease that can be confused with Wernicke encephalopathy (WE). We have reported here the case of a 31-year-old malnourished man who presented with headache, fever, vomiting, diarrhea, and confusion. His imaging and laboratory findings were indicative of WE. His condition improved after treatment with a high dose of vitamin B1 and intravenous administration of methylprednisolone. However, after continuing to take vitamin B1 for 2 weeks, his symptoms and neuroimaging findings worsened. Increased standardized uptake values of positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET) and interleukin-10 (IL-10) in the cerebrospinal fluid led to the diagnosis of PCNSL. After treatment with methotrexate and calcium leucovorin, the symptoms and neuroimaging abnormalities disappeared at the 6-month follow-up examination. The possibility of PCNSL should be considered if the routine treatment for WE are ineffective. 18F-FDG PET and IL-10 may provide a new method for the early diagnosis of PCNSL.

Migraine treatment and healthcare costs: retrospective analysis of the China Health Insurance Research Association (CHIRA) database.

BACKGROUND: Adult migraine remains underdiagnosed and undertreated, despite significant negative effects on physical and emotional functioning. Information on prescribing patterns and treatment costs of migraine in China is limited. METHODS: This retrospective analysis of the China Health Insurance Research Association (CHIRA) medical insurance claims database in 2016 to 2017 evaluated treatment patterns, direct medical costs, and healthcare resource utilization among adults with migraine in mainland China. RESULTS: Of 108,375 patients with headache-related outpatient visits, 10,652 were adults with migraine (mean age 51.4 years, 55.4% female). Common comorbidities were major depressive disorder (4.1%), insomnia (3.8%), and anxiety (2.3%). Migraine patients were prescribed acute medication (26.4%), preventive medication (15.0%), and Chinese patent and herbal medicines (24.5% and 11.7%, respectively). Of patients prescribed acute medication, 68.8% received non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), 7.1% received opioids, while only 3.3% received triptans. Mean annual outpatient costs per patient were 46.5 United States dollars (USD), with mean (standard deviation) 1.8 (2.0) outpatient visits per year. Medication costs for traditional Chinese medicine (22.4 USD per patient) were higher than for Western medicine (13.5 USD). CONCLUSION: Among migraine patients in China, NSAIDs were commonly prescribed as acute medication, while utilization of migraine-specific triptans and preventive medications was low.

Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

Efficacy and Safety of Toutongning Capsule in Patients with Migraine: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: Toutongning (TTN) capsule, a Chinese patent medicine, is used as a prophylactic treatment for migraine. The present study was conducted as a postmarketing evaluation of the efficacy and safety of TTN capsule. Design: A randomized, double-blind, placebo-controlled trial. Location: Patients recruited from 14 medical centers in China from May 2014 to August 2015. Subjects: Patients between 18 and 65 years of age with a diagnosis of migraine. Interventions: The patients were randomly assigned to receive either TTN (1200 mg, three times daily) or a matched placebo (1:1) for 4 weeks. Outcome measures: The primary outcome measured was a minimum 50% reduction in the frequency of headaches from the 4-week baseline period to the last 4 weeks of the 12-week trial. Secondary outcomes included duration, days, and visual analog score of headache attack, interval between headache attacks, usage of acute analgesics, and score on the Headache Impact Test-6. In addition, all patients were evaluated for adverse events (AEs). Results: This study initially enrolled 400 patients; a total of 378 participants completed the experiment while fulfilling all study requirements. TTN had a superior effect compared with the placebo on both the primary and secondary outcome measures without any serious AEs or unexpected side effects. Conclusion: TTN can effectively prevent the occurrence of migraine headaches and is well-tolerated and safe. TTN may exhibit a persistent therapeutic effect even after cessation of use. Trial Registration number: ChiCTR-IPR-15007058.

Dynamic changes in CGRP, PACAP, and PACAP receptors in the trigeminovascular system of a novel repetitive electrical stimulation rat model: Relevant to migraine.

Migraine is the seventh most disabling disorder globally, with prevalence of 11.7% worldwide. One of the prevailing mechanisms is the activation of the trigeminovascular system, and calcitonin gene-related peptide (CGRP) is an important therapeutic target for migraine in this system. Recent studies suggested an emerging role of pituitary adenylate cyclase-activating peptide (PACAP) in migraine. However, the relation between CGRP and PACAP and the role of PACAP in migraine remain undefined. In this study, we established a novel repetitive (one, three, and seven days) electrical stimulation model by stimulating dura mater in conscious rats. Then, we determined expression patterns in the trigeminal ganglion and the trigeminal nucleus caudalis of the trigeminovascular system. Electrical stimulation decreased facial mechanical thresholds, and the order of sensitivity was as follows: vibrissal pad >inner canthus >outer canthus (P < 0.001). The electrical stimulation group exhibited head-turning and head-flicks (P < 0.05) nociceptive behaviors. Importantly, electrical stimulation increased the expressions of CGRP, PACAP, and the PACAP-preferring type 1 (PAC1) receptor in both trigeminal ganglion and trigeminal nucleus caudalis (P < 0.05). The expressions of two vasoactive intestinal peptide (VIP)-shared type 2 (VPAC1 and VPAC2) receptors were increased in the trigeminal ganglion, whereas in the trigeminal nucleus caudalis, their increases were peaked on Day 3 and then decreased by Day 7. PACAP was colocalized with NEUronal Nuclei (NeuN), PAC1, and CGRP in both trigeminal ganglion and the trigeminal nucleus caudalis. Our results demonstrate that the repetitive electrical stimulation model can simulate the allodynia during the migraine chronification, and PACAP plays a role in the pathogenesis of migraine potentially via PAC1 receptor.

Volumetric abnormalities of thalamic subnuclei in medication-overuse headache.

BACKGROUND: The thalamus exerts a pivotal role in pain processing and cortical excitability control and a previous voxel-based morphometry study confirmed increased volume in bilateral thalamus in medication-overuse headache (MOH). The aim of this study is to investigate altered thalamic subnuclei volume in MOH compared with normal controls, and to evaluate the relationship of each thalamic subnuclei volume with the clinical variables. METHODS: High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 27 patients with MOH and 27 normal controls (NC). Thalamic subnuclei templates were created based on Talairach template with MNI space transformation, and the individual thalamic subnuclei templates were generated by applying the deformation field from structural image segment to the thalamic subnuclei templates, and then individual thalamci subnuclei volume were calculated. RESULTS: The whole thalamus and each thalamic subnuclei presented increased volume compared with NC (P < 0.05). The correlation analysis demonstrated that the whole thalamus volume and each thalamic subnuclei volume showed a negative relationship with HAMD scores(P < 0.05), and no any correlation with HAMA, VAS score and disease duration (P > 0.05). CONCLUSION: Increased gray matter volume in the whole thalamus and all the thalamus subnuclei may reflect central sensitization and higher-order of pain alteration in MOH. These structural changes in the thalamus may also be influenced by mood disturbances related to the MOH.

Migraine Prevention Using Different Frequencies of Transcutaneous Occipital Nerve Stimulation: A Randomized Controlled Trial.

This study's objective was to evaluate the efficacy and tolerability of transcutaneous occipital nerve stimulation (tONS) in patients with migraine, and to explore whether different tONS frequencies influenced treatment effectiveness. This was a randomized, controlled trial of tONS for prevention of migraine. Patients were randomized to 1 of 5 therapeutic groups before treatment for 1 month. Groups A through C received tONS at different frequencies (2 Hz, 100 Hz, and 2/100 Hz), group D underwent sham tONS intervention, and group E received topiramate orally. The primary outcomes were the 50% responder rate and headache characteristics. A total of 110 patients completed the study. The 50% responder rate was significantly greater in the groups undergoing active tONS and topiramate, compared with sham-treated group. A significant reduction in headache intensity was noted in each test group compared with the sham group; the groups undergoing tONS at different frequencies did not differ significantly. From baseline to the 1-month treatment period, the tONS group with 100 Hz and topiramate group exhibited significant decreases in headache duration. We conclude that tONS therapy is a new promising approach for migraine prevention. It has infrequent and mild adverse events and may be effective among patients who prefer nonpharmacological treatment. PERSPECTIVE: This article introduces a randomized, controlled trial to illustrate tONS as a new approach for prevention of migraine. It shows tONS is well tolerated and could be considered as a promising treatment for patients who prefer to nonpharmacological therapy.

Recent Approaches and Development of Acupuncture on Chronic Daily Headache.

Chronic daily headache (CDH) is a very important part of primary headache disorder, and it causes heavy socioeconomic burden. An increasing number of people are suffering from CDH, and there are many treatment choices for the different subtypes of CDH. However, the definite effect of these treatments, especially the non-pharmacologic treatments, is still unclear and controversial. Acupuncture, a key component of Traditional Chinese Medicine (TCM), has an over 2500-year history in China as an effective non-pharmacologic method for chronic pain, but the researches on CDH are limited. Varying stimulations and the acupoints can be chosen for different acupuncturists, and there are many primary and secondary assessments of the therapeutic effect. Although acupuncture has been shown to have potential effects on CDH, it requires much deeper researches on the optimized usage and underlying mechanisms.

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Duliang Soft Capsule in Patients with Chronic Daily Headache.

Objective. To investigate the efficacy and safety of traditional Chinese medicine Duliang soft capsule (DSC) in prophylactic treatment for patients with chronic daily headache (CDH). Methods. A multicenter, double-blind, randomized, placebo-controlled clinical study was conducted at 18 Chinese clinical centers. The participants received either DSC or placebo for 4 weeks. The primary efficacy measure was headache-free rate (HFR) in a 4-week period between the pretreatment and posttreatment stages. The secondary efficacy measures were the decrease of headache days, the duration of headache attacks, the frequency of analgesic usage, quality of life, disability, and the headache severity (VAS scores). The accompanying symptoms and adverse events were also assessed. Results. Of 584 CDH patients assessed, 468 eligible patients were randomized. 338 patients received DSC, while 111 patients were assigned in the placebo group. Following treatment, there was a 16.56% difference in HFR favoring DSC over placebo (P < 0.01). Significant differences were also observed between DSC and placebo groups in the secondary measures. However, no statistical difference was found between the two groups in the associated symptoms. No severe adverse effects were observed in the study. Conclusions. DSC might be an effective and well-tolerated option for the prophylactic treatment of patients with CDH.

Abnormal coactivation of the hypothalamus and salience network in patients with cluster headache.

OBJECTIVE: The purpose of this study was to investigate whether the resting-state coactivation of the hypothalamus, both ipsilateral and contralateral to the headache side, and the salience network (SN) was altered in patients with cluster headache (CH) in the headache attack remission state in the cluster period, and to reveal possible pathogenesis of CH attacks and gain further insight into the pathophysiology of CH. METHODS: Resting-state fMRI scans of 21 patients with CH were obtained (13 with right-sided headache and 8 with left-sided headache) and 21 age- and sex-matched normal controls. The resting-state fMRI data were analyzed using independent component analysis to identify the group differences of hypothalamic-SN coactivation between the patients with CH and healthy controls. RESULTS: Decreased functional coactivation was detected between the hypothalamus, both ipsilateral and contralateral to the headache side, and the SN both in patients with right-sided CH and in those with left-sided CH. CONCLUSION: Our findings suggest that the decreased hypothalamus-SN coactivation may have a role in CH attacks by the defective central pathway of pain control and autonomic nervous system dysregulation. This helps to gain additional insight into the pathophysiologic basis of CH and the nature of the brain dysfunction in CH.

Prospective induction of peripheral neuropathy by the use of Tartarian Buckwheat.

Tartarian Buckwheat is an effective hypoglycemic medicinal herb. Its main active ingredients are flavonoids. We report here 5 cases of new onset polyneuropathy with dyskinesia prospectively induced by tartarian buckwheat products. Clinical and electrophysiological evidence along with laboratory tests were reviewed and analyzed. All patients were male, with an average age of 52.2 ± 10.9 years old (range: 40-66 years) and had a recent history of using tartarian buckwheat for diabetes therapy. The average time of use was 2.5 ± 1.0 months (range: 1.5-4 months). The average duration of the clinical course was 0.9 ± 0.2 months (range: 0.5-1 months). Symptoms included numbness and weakness of the limbs (5/5, 100%), hoarseness (4/5, 80%), dysphagia (1/5, 20%), bilateral facial paralysis (1/5, 20%), urinary disorders (3/5, 60%) and gonadal abnormality (4/4, 100%). Nerve conduction studies suggested more severe damages in motor nerves than sensory nerves. All the patients showed abnormality on Von Frey filaments determination. Hence, tartarian buckwheat products may cause toxic peripheral nerve lesion and the use of herbal medication needs to be better regulated and closely monitored.

Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review.

Motor neuron hyperexcitability (MNH) indicates a disorder characterized by an ectopic motor nerve discharge on electromyogram (EMG). Here, we present a series of three cases of subacute MNH with mercury poisoning. The first case showed hyperhidrosis, insomnia, generalied myokymia, cramps, tremor, weight loss, and myokymic and neuromyotonic discharges, followed by encephalopathy with confusion, hallucinations, and memory decrease. The second case was similar to the former but without encephalopathic features. The third case showed widespread fasciculation, fatigue, insomnia, weight loss, and autonomic dysfunction, including constipation, micturition difficulty, and impotence, with multiple fibrillation, unstable fasciculation, widened motor neuron potential, and an incremental response at high-rate stimulation in repetitive nerve stimulation. Based on the symptoms, the three cases were diagnosed as Morvan's syndrome, Isaacs' syndrome, and Lambert-Eaton myasthenic syndrome with ALS-like syndrome, respectively. Mercury poisoning in the three cases was confirmed by analysis of blood and urine samples. All cases recovered several months after chelation therapy and were in good condition at follow-up. Very few cases of MNH linked with mercury exposure have been reported in the literature. The mechanism of mercury-induced MNH may be associated with ion channel dysfunction.

Elevated audiovisual temporal interaction in patients with migraine without aura.

BACKGROUND: Photophobia and phonophobia are the most prominent symptoms in patients with migraine without aura. Hypersensitivity to visual stimuli can lead to greater hypersensitivity to auditory stimuli, which suggests that the interaction between visual and auditory stimuli may play an important role in the pathogenesis of migraine. However, audiovisual temporal interactions in migraine have not been well studied. Therefore, our aim was to examine auditory and visual interactions in migraine. METHODS: In this study, visual, auditory, and audiovisual stimuli with different temporal intervals between the visual and auditory stimuli were randomly presented to the left or right hemispace. During this time, the participants were asked to respond promptly to target stimuli. We used cumulative distribution functions to analyze the response times as a measure of audiovisual integration. RESULTS: Our results showed that audiovisual integration was significantly elevated in the migraineurs compared with the normal controls (p < 0.05); however, audiovisual suppression was weaker in the migraineurs compared with the normal controls (p < 0.05). CONCLUSIONS: Our findings further objectively support the notion that migraineurs without aura are hypersensitive to external visual and auditory stimuli. Our study offers a new quantitative and objective method to evaluate hypersensitivity to audio-visual stimuli in patients with migraine.