Prevalence of cardiac right left shunts in migraine: a population-based case–control study

We aimed to investigate the prevalence of cardiac right left shunts (RLS) in population-based samples of subjects with migraine with aura (n = 42), migraine without aura (n = 44) and controls without headache (n = 41). Cardiac RLS was assessed with transcranial Doppler sonography with intravenous injection of saline. Prevalence of RLS was highest in migraineurs with aura (45.2%) compared to migraineurs without aura (34.1%) and controls (41.5%). Permanent as opposed to latent RLS was more common among patients with migraine with aura (40.5%) than in patients with migraine without aura (23.3%) or controls (24.4%). Differences did not reach statistical significance between the three groups (p = 0.564 for RLS prevalence, p = 0.349 for prevalence of permanent shunts). Our data implicate a trend towards higher prevalence of RLS with larger shunts in subjects with migraine with aura.     

Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity

Previous studies of lymphocyte distribution in schizophrenia have yielded inconsistent results, as summarized in the present study. Based on our own original data, potential confounds that might explain these variations are analyzed and discussed. Blood samples from 26 patients with acute paranoid schizophrenia were investigated in comparison with 32 matched healthy controls by flow cytometry (CD3, CD4, CD8, CD19, and CD56 phenotyping). A subgroup of drug-free patients was followed up after 6 weeks of treatment. Cotinine levels and the free cortisol index (FCI) were provided in order to control for medication, smoking, and stress. Cotinine levels correlated with natural killer (NK) cell counts (CD3^?/CD56⁺: r = ?0.383, P = 0.003) while the FCI was related to B cell numbers (CD19⁺: r = 0.390, P = 0.003). Considering these covariates, a lower level of T helper cells (P = 0.010), a reduced CD4/CD8 ratio (P = 0.029), and elevated B cells (P = 0.008) were found during acute psychosis. After 6 weeks of medication, an inverse pattern was observed in initially drug-free patients: total T cell (P = 0.005), T helper (P = 0.003), and T suppressor/cytotoxic cells (P = 0.005) increased, while B cell counts declined (P = 0.049). In conclusion, acute paranoid schizophrenia may be accompanied by a reduced T cell defense and a shift towards B cell immunity, which normalizes in response to treatment. In addition to disease stage or subtype and medication, cigarette smoking and stress are important co-factors.     

Addenbrooke’s cognitive examination test for brief cognitive assessment of adolescents suffering from migraine with aura

The aim of this study was to assess the role of the Addenbrooke’s cognitive examination test (ACE-R) in the evaluation of cognitive status in migraineurs interictally. A total of 44 adolescent patients and 44 healthy controls, matched by age and gender, have undergone ACE-R testing. Migraineurs were additionally questioned about migraine aura features and presence of higher cortical dysfunctions (HCD) during an aura. According to the questionnaire results, patients were subsequently divided into HCD and Non-HCD group. ACE-R scores of migraine patients were significantly lower than in healthy controls (93.68 ± 3.64 vs 96.91 ± 2.49; t = 4.852, p < 0.001). Also, subscores of memory and verbal fluency were significantly higher in the control population. There was no correlation of HCD occurrence with cognitive examination score, although Non-HCD subgroup achieved better score (93.13 ± 3.91 vs 94.29 ± 3.30; t = 1.053, p = 0.298). Findings have shown that migraineurs get lower ACE-R test scores, with a tendency to have a poorer outcome in more complex aura. Also, our study has revealed that the ACE-R test is an easily administered test for brief assessment of cognitive status in migraineurs. Future perspectives could be further evaluation of ACE-R test in larger sample size and the impact of migraine with aura on cognitive function in adolescents.     

Change and predictive ability of circulating immunoregulatory lymphocytes in long-term outcomes of acute ischemic stroke

Lymphocytes play an important role in the immune response after stroke. However, our knowledge of the circulating lymphocytes in ischemic stroke is limited. Herein, we collected the blood samples of clinical ischemic stroke patients to detect the change of lymphocytes from admission to 3 months after ischemic stroke by flow cytometry. A total of 87 healthy controls and 210 patients were enrolled, and the percentages of circulating T cells, CD4⁺ T cells, CD8⁺ T cells, double negative T cells (DNTs), CD4⁺ regulatory T cells (Tregs), CD8⁺ Tregs, B cells and regulatory B cells (Bregs) were measured. Among patients, B cells, Bregs and CD8⁺ Tregs increased significantly, while CD4⁺ Tregs dropped and soon reversed after ischemic stroke. CD4⁺ Tregs, CD8⁺ Tregs, and DNTs also showed high correlations with the infarct volume and neurological scores of patients. Moreover, these lymphocytes enhanced the predictive ability of long-term prognosis of neurological scores when added to basic clinical information. The percentage of CD4⁺ Tregs within lymphocytes showed high correlations with both acute and long-term neurological outcomes, which exhibited a great independent predictive ability. These findings suggest that CD4⁺ Tregs can be a biomarker to predict stroke outcomes and improve existing therapeutic strategies of immunoregulatory lymphocytes.     

Efficacy of Ginkgolide B in the prophylaxis of migraine with aura

In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll^®), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 ± 2.2 in the run-in period, to 2.0 ± 1.9 during TI and to 1.2 ± 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 ± 19.4 min during run-in, 28.2 ± 19.9 during TI, and 17.6 ± 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll^® administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.

     

Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind,randomized, multicenter,Italian study

Migraine with aura affects ~20–30 % of migraineurs and it is much less common than migraine without aura. The aim of this study was to compare the efficacy of frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with aura. Analysis was carried out in a subset of 18 subjects with migraine with aura (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double-blind, cross-over study. According to the study design, each patient had to treat three episodes of migraine in no more than 3 months with one drug, before switching to the other treatment. The rate of pain-free episodes at 2 h was significantly (p < 0.05) larger under frovatriptan (45.8 %) than under zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent episodes were similar between the two treatments, while sustained pain-free episode was significantly (p < 0.05) more frequent during frovatriptan treatment (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior to zolmitriptan in the immediate treatment of patients with migraine with aura, and it is capable of maintaining its acute analgesic effect over 48 h.     

Clinical characteristics of menstrually related and non-menstrual migraine

Migraine attacks increase during the perimenstrual period in approximately half of female migraineurs. There are differences in the pathogenesis and clinical features of menstrually related and non-menstrual migraine attacks. The objective of this study was to compare the characteristics of migraine in patients with menstrually related and non-menstrual migraine, and to investigate the differences between premenstrual, menstrual, and late-menstrual migraine attacks. Three-hundred and thirty-two women with migraine without aura were evaluated using questionnaires and diaries to determine the characteristics of headache, preceding and accompanying symptoms, and the relation of migraine attacks and menstruation. One-hundred and sixty-three women had menstrually related migraine without aura (49.1%). Duration of disease and duration of headache were longer (p = 0.002 and p < 0.001, respectively), and nausea, vomiting, phonophobia, and aggravation of headache with physical activity were more frequent in patients with menstrually related migraine (p = 0.005, p = 0.006, p < 0.001 and p = 0.006, respectively). Premonitory symptoms and allodynia were observed more frequently in the menstrually related migraine group (p = 0.012 and p = 0.004, respectively). Perimenstrual migraine attacks occurred premenstrually (days ?2 and ?1) in 46 patients (25.3%), menstrually (days 1 to 3) in 90 patients (49.4%), and late menstrually (days 4 to 7) in 19 patients (10.4%). Our results showed that the duration of headache was longer and accompanying symptoms were more frequent and diverse in patients with menstrually related migraine without aura, suggesting that these findings may reflect the increase in excitability or susceptibility of the brain in these patients.     

Nutraceuticals safety and efficacy in migraine without aura in a population of children affected by neurofibromatosis type I

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders with a prevalence of one in 4,000 people worldwide, associated with many neurological comorbidities, such as headache. Despite the high prevalence of headache in this population, little data exist regarding the classification of headaches experienced by patients with NF1. Aim of this study is to verify the efficacy and safety of a nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for prophylaxis in a sample of children affected by NF1 presenting migraine without aura. Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex was orally administered twice a day for 6 months, to 18 school-aged patients with NF1 and presenting symptoms of migraine without aura (10 M, mean age 8.4 ± 1.65). Each patient kept a journal to record: number, intensity (according VAS scale), duration of attacks and concomitant symptoms. In addition, the PedMIDAS scale was administered to assess migraine-related disability. To verify the efficacy of the association, we tested the starting frequency (T ₀) of headache after 6 months (T ₁) and then we calculated the migraine frequency delta percentage to express the decrease in monthly frequency. After treatment, a reduction was reported (p < 0.001) in all migraine outcomes (frequency, duration, intensity, and grade of disability). In conclusion, the present study should be considered as the first report on the efficacy and safety of nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for the prophylaxis of migraine in children affected by NF1. Our findings suggest that headache symptoms should be considered a therapeutic target independent of primary disorder.     

Neuroimmune processes associated with Wallerian degeneration support neurotrophin‐3‐induced axonal sprouting in the injured spinal cord

Lesions of the spinal cord cause two distinctive types of neuroimmune responses, a response at the lesion site that leads to additional tissue destruction and a more subtle response, termed Wallerian degeneration (WD), that occurs distal to the lesion site. We have evidence that the neuroimmune response associated with WD may support tissue repair. Previously, we found that overexpression of neurotrophin‐3 (NT‐3) induced axonal growth in the spinal cord after a unilateral corticospinal tract (CST) lesion, but only if the immune system was intact and activated. We reasoned that a neuroimmune response associated with WD was involved in this neuroplasticity. To test this, we compared NT‐3‐induced axonal sprouting in athymic nude rats that lack functional T cells with rats with functional T cells and in nude rats grafted with CD4⁺ T cells or CD8⁺ T cells. There was no sprouting in nude rats and in nude rats grafted with CD8⁺ T cells. However, nude rats grafted with CD4⁺ T cells mounted a sprouting response. To determine which CD4⁺ subtype, type 1 T helper (Th1) or type 2 T helper (Th2) cells, was responsible, we grafted Th1 and Th2 cells into nude rats and tested whether they would support sprouting. Axonal sprouting was greater in rats grafted with Th2 cells, demonstrating that the Th2 subtype was responsible for supporting axonal sprouting. These data suggest that WD activates Th2 cells that, along with the direct effects of NT‐3 on CST axons, act to support axonal sprouting in the lesioned spinal cord. © 2013 Wiley Periodicals, Inc.     

Characteristics and clinical correlates of white matter changes in brain magnetic resonance of migraine females

Objective

White matter hyperintensities (WMHs) were often found in migraine patients. The aim of study was to characterize WMHs, assess their prevalence, determine relationship to clinical symptoms and homocysteine levels in migraine females.

Regulatory T cells increased while IL-1β decreased during antidepressant therapy

Background

Regulatory T cells (Tregs, CD4⁺CD25^hi) are specialized in steering the immune response and cytokine release to maintain tolerance to self-antigens. As cytokines such as interleukin (IL)-1β, IL-6 and interferon (IFN)-α have been shown to be involved in the pathophysiology of depression and cytokine levels have been shown to change during successful antidepressant treatment, we tested the involvement CD4⁺CD25^hi Tregs in these immunological processes during antidepressant therapy.

Methods

16 patients suffering from a depressive episode were included into the study and treated with antidepressants according to their doctor’s choice. Blood samples were collected during the first week after admission and after 6 weeks of treatment. Therein, we determined plasma levels of IL-1β, and measured IL-1β, IL-6 and IFN-α levels in the stimulated blood by performing a whole blood assay. We distinguished lymphocytes and identified CD4⁺CD25^hi Tregs by multiparameter flow cytometry. The psychopathological status was assessed using the Hamilton Depression Rating Scale (HAMD-21).

Results

HAMD-21 score, IL-1β serum levels as well as LPS-stimulated IL-1β and IL-6 production had decreased significantly at the end of treatment. In contrast, the amount of CD4⁺CD25^hi cells increased significantly from 2.74% ± 0.88 (mean value ± standard deviation) to 3.54% ± 1.21; p = 0.007. No significant changes in virus-induced IFN-α production was observed.

Conclusions

The increase in CD4⁺CD25^hi Tregs during antidepressant therapy may be the reason for the decrease in cytokine production and the recovery from depression.     

Structural brain MRI abnormalities in pediatric patients with migraine

Morphometric MRI studies in adult patients with migraine have consistently demonstrated atrophy of several gray matter (GM) regions involved in pain processing. We explored the regional distribution of GM and white matter (WM) abnormalities in pediatric patients with episodic migraine and their correlations with disease clinical manifestations. Using a 3.0 T scanner, brain T2-weighted and 3D T1-weighted scans were acquired from 12 pediatric migraine patients and 15 age-matched healthy controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (p < 0.05, family-wise error corrected). Compared to controls, pediatric migraine patients experienced a significant GM atrophy of several regions of the frontal and temporal lobes which are part of the pain-processing network. They also had an increased volume of the right putamen. The left fusiform gyrus had an increased volume in patients with aura compared to patients without aura and controls, whereas it was significantly atrophied in patients without aura when compared to the other two groups. No abnormalities of WM volume were detected. In migraine patients, regional GM atrophy was not correlated with disease duration and attack frequency, whereas a negative correlation was found between increased volume of the putamen and disease duration (r = ?0.95, p < 0.05). These results show that GM morphometric abnormalities do occur in pediatric patients with migraine. The presence of such abnormalities early in the disease course, and the absence of correlation with patient clinical characteristics suggest that they may represent a phenotypic biomarker of this condition.     

Ictal autoscopic phenomena and near death experiences: a study of five patients with ictal autoscopies

Autoscopic phenomena in general may—among other conditions—occur during epileptic seizures and near death experiences. We set the hypothesis that ictal autoscopic phenomena and near death experiences have a similar semiology as measured by the Near Death Experience Questionnaire. We also investigated whether patients with aura before temporal lobe seizures with or without autoscopic phenomena could be distinguished by this questionnaire. For these purposes, we examined five patients with ictal autoscopy and 12 patients with aura before temporal lobe seizures without ictal autoscopy as controls. We used a cut-off of 7 points or higher on the Near Death Experience Questionnaire for indicating the semiology of a near death experience and for distinguishing patients with ictal autoscopy from controls. This cut-off separated patients with ictal autoscopic phenomena from aura before temporal lobe seizures without autoscopy (p = 0.0002, two-sided, exact Fisher’s Test; specificity: 100 % [CI95 % 77.9 and 100 %], sensitivity: 100 % [CI95 % 54.9 and 100 %]). Furthermore, all autoscopic patients (range 7–10) and none of the controls (range 0–5) had scores of 7 points or higher. Thus, the individual experiences during simple partial autoscopic seizures and near death experiences are similar, at least in some prominent aspects. These findings might be of particular interest for the pathophysiology of near death experiences, as all patients with ictal autoscopic phenomena had an epileptic dysfunction at the temporo-parietal junction or its neighboring regions. Therefore, a malfunction of this brain region might also be involved in near death experiences of other origins especially during states which could cause a near death experience and a cerebral excitability.     

Familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming α₁ subunits of the neuronal voltage-gated Ca²⁺ channels Ca_v2.1 and Na⁺ channels Na_v1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the α₂ subunit of the Na⁺, K⁺ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca_v2.1 channel and, as a consequence, increased Ca_v2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the α₂ Na⁺,K⁺-ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na_v1.5 (and presumably Na_v1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K⁺ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K⁺ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategics that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.     

Treatment with telmisartan,a long-acting angiotensin II receptor blocker,prevents migraine attacks in Japanese non-responders to lomerizine

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50–75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.     

An innovative approach for migraine prevention in young age: a preliminary study

Headache is one of the commonest conditions to affect children and adolescents in industrialized countries. Effective pharmacological treatments without side effects are still lacking. Ginkgolide B, an herbal constituent extract from ginkgo biloba tree leaves, is a natural antiplatelet activating factor (PAF). PAF is a potent proinflammatory and nociceptive agent released during the inflammation process. Therefore, Ginkgolide B can be considered a promising non-pharmacological tool for treatment of migraine with and without aura. We propose to determine the efficacy of Ginkgolide B as preventive treatment in a group of young patients suffering from migraine without aura. A small sample of 24 young patients suffering from migraine without aura entered the open-label prospective trial. Migraine without aura was diagnosed according to International Headache Society criteria. The treatment was well tolerated and the compliance was good. These preliminary data show that Ginkgolide B seems to be effective as preventive treatment in reducing migraine attack frequency and in attenuating the use of symptomatic medication in our small series of children with primary headache.

     

Association of depression,anxiety and post-traumatic stress disorder with migraine: Data from Kosovo

Introduction

Migraine is ranked as the seventh leading cause of disability worldwide, and it is characterized by a manifestation of combined neurological, gastrointestinal, and autonomic symptoms linked with different provoking factors.

Predictors of Triptan Response in Pediatric Migraine

BackgroundMigraine is common in children and adolescents and can be disabling. Being able to predict which patients will respond to triptans based on their clinical phenotype would be helpful. Adult data suggest cranial autonomic symptoms and aura predict triptan response. This study examined clinical predictors of triptan response in pediatric migraineurs.MethodsThis chart review study included all patients less than 18 years old with migraine who were seen at the University of California, San Francisco Headache Center in 2014. Univariate χ² analyses were performed, followed by multivariate logistic regression modeling.ResultsOf 127 pediatric migraineurs, 70 (55%) had chronic migraine and 24 (19%) had aura. The majority (55%) had at least one cranial autonomic symptom. Of 65 with triptan outcome data, 47 (73%) benefitted from a triptan. In univariate analyses, triptan benefit was seen in 65% with chronic migraine versus 88% with episodic migraine (P = 0.048), 67% with aura versus 74% without (P = 0.66), and 70% with cranial autonomic symptom versus 74% without (P = 0.76). In a multivariate logistic regression model, chronic migraine, aura, and cranial autonomic symptom were not statistically significant predictors of triptan benefit: chronic migraine: 0.25 (0.06-1.04); aura: 0.65 (0.09-4.45); cranial autonomic symptom: 0.75 (0.22-2.52).ConclusionsIn univariate analysis, individuals with chronic migraine were less likely to benefit from triptans. In contrast to what has been documented in adults, cranial autonomic symptoms and aura did not predict triptan response, although our small sample size limited the study's power. Larger pediatric studies are needed, and future pediatric triptan trials should provide response rates stratified by clinical variables such as aura.     

Pathophysiology of migraine attack with prolonged aura revealed by transcranial Doppler and near infrared spectroscopy

The aim of this study is to identify the pathophysiology of migraine attack with prolonged aura (between 1 h and 7 days) not clearly understood. We studied cortical cerebral microcirculation by an innovative near infrared spectroscopy system (NIRS) and cerebral macrocirculation by trancranial Doppler (TCD) in eight subjects (3 M and 5 F, age range 21–41 years) during spontaneous prolonged migraine aura and after 1, 2, 4, 6, 12 and 24 h since the end of aura and compared the results with the headache-free periods. During aura NIRS showed a significant decrease of the arterial pulse wave of cerebral microcirculation (APWCM) amplitude (−35%), p < 0.002, and an increase of cerebral tissue oxygen saturation (SctO₂) (+15%), p < 0.008 ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods; TCD showed a significant increase of pulsatility index (+38%), p < 0.001 and a significant decrease of the diastolic velocity in the posterior and middle cerebral artery ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods. During prolonged migraine aura we found areas of cortical hypoperfusion corresponding to the topography of aura symptoms that were the result of a decreased metabolic demand rather than ischemic mechanism.

     

The sympathetic nervous system modulates CD4+Foxp3+ regulatory T cells via noradrenaline-dependent apoptosis in a murine model of lymphoproliferative disease

The sympathetic nervous system (SNS) plays a crucial role in the course and development of autoimmune disease in Fas-deficient lpr/lpr mice. As regulatory T cells (Tregs) are considered important modulators of autoimmune processes, we analyzed the interaction between the SNS and Tregs in this murine model of lymphoproliferative disease. We found that the percentage of Tregs among CD4⁺ T cells is increased in the spleen, lymph nodes, and thymus of lpr/lpr mice as compared to age-matched C57Bl/6J (B6) mice. Furthermore, noradrenaline (NA), the main sympathetic neurotransmitter, induced apoptosis in B6- and lpr/lpr-derived Tregs. NA also reduced the frequency of Foxp3⁺ cells and Foxp3 mRNA expression via β₂-adrenoceptor (β₂-AR)-mediated mechanisms in a concentration and time-dependent manner. Destruction of peripheral sympathetic nerves by 6-hydroxydopamine significantly increased the percentage of Tregs in B6 control mice to an extent comparable to aged-matched lpr/lpr mice. The concentration of splenic NA negatively correlated with the frequency of CD4⁺Foxp3⁺ Tregs. Additionally, 60 days after sympathectomy, a partial recovery of NA concentrations led to Treg percentages comparable to those of intact, vehicle-treated controls. Immunohistochemical analysis of the spleen revealed localization of single Foxp3⁺ Tregs in proximity to NA-producing nerve fibers, providing an interface between Tregs and the SNS. Taken together, our data suggest a relation between the degree of splenic sympathetic innervation and the size of the Treg compartment. While there are few examples of endogenous substances capable of affecting Tregs, our results provide a possible explanation of how the magnitude of the Treg compartment in the spleen can be regulated by the SNS.