Thalamic nuclei volumes and network in juvenile myoclonic epilepsy.

OBJECTIVE: The aim of this study was to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with juvenile myoclonic epilepsy (JME) compared to healthy controls. METHODS: We enrolled 50 patients with JME and 42 healthy controls. We obtained structural volumes of the individual thalamic nuclei based on T1-weighted imaging and performed intrinsic thalamic network analysis using graph theoretical analysis. We analyzed the differences of thalamic nuclei volumes and intrinsic thalamic networks between the patients with JME and healthy controls. RESULTS: In the patients with JME, there were significant alterations of thalamic nuclei volumes compared to healthy controls. Right laterodorsal and left suprageniculate nuclei volumes were significantly increased (0.0019% vs 0.0014%, P < .0001; 0.0011% vs 0.0008%, P = .0006, respectively), whereas left ventral posterolateral, left ventromedial, and left pulvinar inferior nuclei volumes (0.0572% vs 0.0664%, P = .0001; 0.0013% vs 0.0015%, P = .0002; 0.0120% vs 0.0140%, P < .0001, respectively) were decreased in the patients with JME. Furthermore, the intrinsic thalamic network of the patients with JME was significantly different from that of the healthy controls. The modularity in the patients with JME was significantly increased over that in healthy controls (0.0785 vs 0.0212, P = .039). CONCLUSION: We found that there were significant alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with JME compared to healthy controls. These findings might contribute to the underlying pathogenesis of in JME.

Characteristics of Perfusion Computed Tomography Imaging in Patients with Seizures Mimicking Acute Stroke.

INTRODUCTION: Seizures as acute stroke mimics are a diagnostic challenge. OBJECTIVE: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. METHODS: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. RESULTS: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). CONCLUSIONS: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.

Alterations of the brain network in idiopathic rapid eye movement sleep behavior disorder: structural connectivity analysis.

PURPOSE: To evaluate and compare structural connectivity using graph theoretical analysis in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy subjects. METHODS: Ten consecutive patients with iRBD were recruited from a single tertiary hospital. All patients had normal brain magnetic resonance imaging results on visual inspection. They did not have any other neurological disorder. Control subjects were also enrolled. All subjects underwent three-dimensional volumetric T1-weighted imaging. Absolute structural volumes were calculated using FreeSurfer image analysis software. Structural volume and connectivity analyses were performed with Brain Analysis using Graph Theory. RESULTS: Compared to healthy controls, patients with iRBD showed significant alterations in cortical and subcortical volumes, showing increased volumes of frontal cortex, thalamus, and caudate nucleus. In addition, patients with iRBD exhibited significantly different structural connectivity compared to healthy controls. In measures of global network, average degree, global efficiency, and local efficiency were decreased whereas characteristic path length was increased in iRBD patients. In measures of local network, there was significant hub reorganization in patients with iRBD. Betweenness centrality of caudate nucleus and frontal cortex was increased in patients with iRBD. CONCLUSIONS: This is the first study to report that structural volume and connectivity in patients with iRBD are significantly different from those in healthy controls. iRBD patients exhibited disrupted topological disorganization of the global brain network and hub reorganization. These alterations are implicated in the pathogenesis of iRBD. They might be potential biomarkers of iRBD.

Increased Superoxide Dismutase 2 by Allopregnanolone Ameliorates ROS-Mediated Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus.

Excessive production of reactive oxygen species (ROS), along with dysfunction of the antioxidant defense system, such as that involving superoxide dismutase (SOD), may play a major role in neuronal death following status epilepticus (SE). Neurosteroids, which are allosteric modulators of the GABAA receptor in cerebral metabolism, have been suggested as being neuroprotective in various animal models; however, their effect to preventing ROS has not been examined. Herein, we investigate the neuroprotective role of allopregnanolone, the prototypical neurosteroid in the brain, in relation to the ROS-mediated neuronal injury. Adult male C57BL/6 mice were subjected to SE and treated with allopregnanolone. Hippocampal cell death was assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and ROS production was investigated by in situ detection of oxidized hydroethidine. SOD2 expression was analyzed by both western blot and immunofluorescent staining in the hippocampal subfields. In mice treated with allopregnanolone after SE, hippocampal cell death, DNA fragmentation, oxidative DNA damage, and ROS production were reduced significantly compared to mice subjected to vehicle treatment after SE. Hippocampal SOD2 expression was significantly increased by allopregnanolone. These finding suggest that allopregnanolone plays a neuroprotective role, with not only anticonvulsant but also antioxidant effects, by increasing SOD2 in pilocarpine-induced SE model.

Is Transient Global Amnesia a Network Disease?

BACKGROUND: We evaluated a brain network using graph theoretical analysis and microstructural abnormalities of the white matter in patients with transient global amnesia (TGA). METHODS: Twenty patients with TGA and healthy control subjects were recruited, and they underwent diffusion tensor imaging (DTI) scans. Graph theory was applied to obtain network measures based on DTI data. We investigated the network measures and microstructural abnormalities of white matter using tract-based spatial statistics (TBSS) analysis in the patients with TGA. RESULTS: Measures of global topology were not different between the patients with TGA and healthy subjects. However, there were significant differences of hubs organization; the strength of the right superior and inferior orbitofrontal, the right inferior frontal operculum, the left superior parietal, and left postcentral gyrus, the cluster coefficient of the right middle orbitofrontal and left inferior parietal gyrus, the betweenness centrality of the left angular gyrus, and the pagerank centrality of the right superior and inferior orbitofrontal, right inferior frontal operculum, left superior parietal, and left postcentral gyrus in the patients with TGA were significantly lower than those in healthy subjects. Regarding the analysis of the white matter microstructure with TBSS, there were no differences in the fractional anisotropy and mean diffusivity values between the 2 groups. CONCLUSIONS: We newly identify a reorganization of network hubs of the brain network in patients with TGA, especially in the regions of the default-mode network. These alterations of the brain network may play a role in the pathophysiologic mechanism underlying TGA and suggest that TGA is a network disease.

Brain Morphology in Patients with Genetic Generalized Epilepsy: Its Heterogeneity among Subsyndromes.

BACKGROUND: We aimed to evaluate the brain morphology of patients with genetic generalized epilepsy (GGE) compared to healthy subjects. In addition, we investigated whether there are differences in brain morphology among different GGE syndromes. METHODS: We enrolled 100 patients with a clinical diagnosis of GGE. The patients were classified into different syndrome groups according to their predominant seizure type, age of seizure onset, and electroencephalography characteristics (12 childhood absence epilepsy [AE], 13 juvenile AE, 56 juvenile myoclonic epilepsy, and 19 epilepsy with generalized tonic-clonic alone). We used surface-based morphometry of brain magnetic resonance imaging to evaluate brain morphology. RESULTS: We found significantly widespread alterations of brain morphology, including cortical thickness and volumes in several regions in the patients with GGE compared to healthy controls. In addition, we observed significant differences in alterations of cortical thickness and volumes among the different GGE syndromes. However, there were no differences in cortical surface areas between the patients with GGE and healthy controls. There was a significantly negative correlation between the duration of epilepsy and most of the each measures of abnormal brain morphology. CONCLUSIONS: The main finding of this study is that brain morphology in patients with GGE is significantly different from that in healthy controls. In addition, we found that the different GGE syndromes show distinct structural brain morphology, especially cortical thickness, which can help us understand the pathogenesis of GGE syndromes.

Disclosure management behaviors in Korean adults with well-controlled epilepsy: Their relation to perception of stigma.

PURPOSE: In spite of the fact that epilepsy is a concealable stigmatized identity, there is little evidence pertaining to disclosure management in adults living with epilepsy. We determined the factors contributing to disclosure management strategies in adults living with well-controlled epilepsy. METHODS: This was a cross-sectional multicenter study. Korean adults whose seizures had remitted for at least one year participated in this study. Using statistical analyses, we determined whether disclosure management behaviors measured using the Disclosure Management Scale (DMS) were related to demographic, clinical, and psychosocial variables. The Stigma Scale and Hospital Anxiety Depression Scale (HADS) were used. RESULTS: Of a total of 225 participants, 76% stated that they often or sometimes kept their epilepsy a secret, while 24% reported that they never or rarely kept their diagnosis hidden. The mean DMS score was 6.1 (SD=2.4). In univariate analyses, the DMS scores were significantly related to the HADS depression scores (r=0.187, p=0.005) and the presence of perceived stigma (p=0.001). In linear regression analyses, perceived stigma was identified only as an independent factor associated with DMS scores (p=0.031), while HADS depression lost significance (p=0.057). The presence of perceived stigma explained only 4.6% of the variance in DMS scores. CONCLUSIONS: Our study shows that over 70% of Korean adults with well-controlled epilepsy often or sometimes keep their epilepsy a secret. Although perceived stigma is associated with concealment behaviors, it accounts for only a small proportion of the variance in disclosure management.

Clinical Significance of Fluid-Attenuated Inversion Recovery Vascular Hyperintensities in Borderzone Infarcts.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensities (FVHs) are seen in some cases with cerebral hemodynamic impairment and collateral flow. Because the worst outcomes of patients with borderzone infarcts were mainly correlated with impaired hemodynamics, the presence of FVH might provide another clue for predicting the prognosis of patients with borderzone infarcts. METHODS: We reviewed 1377 consecutive patients with ischemic stroke. Cortical borderzone (CBZ) and internal borderzone infarcts were selected based on diffusion-weighted imaging. FVHs were defined as tubular- or serpentine-shaped hyperintensities in the subarachnoid space. We investigated the clinical significance of FVHs in borderzone-infarcted patients. RESULTS: Among 87 patients with borderzone infarcts, the presence of FVH was observed in 30 (34.5%). We identified 62 patients with CBZ infarcts and 25 patients with internal borderzone infarcts. In the cases with CBZ infarcts, the initial National Institutes of Health Stroke Scale scores and the portions of nonfavorable outcome at 3 months in the FVH(+) group were significantly higher than in the FVH(-) group (P<0.05 and P<0.001, respectively). Unlike the cases with CBZ infarcts, there were no significant differences of these clinical features between the FVH(+) group and the FVH(-) group in the patients with internal borderzone infarcts. CONCLUSIONS: The findings of FVH are associated with relatively severe clinical presentation and nonfavorable prognosis in patients with CBZ infarcts, but not in patients with internal borderzone infarcts. The presence of FVH may help to identify CBZ-infarcted patients who require close observation and hemodynamic control.

Atrophy of the pedunculopontine nucleus region in patients with sleep-predominant seizures: A voxel-based morphometry study.

Non-rapid eye movement (NREM) sleep increases interictal epileptiform discharges and frequency of seizures, whereas REM sleep suppresses them. The pedunculopontine nucleus (PPN), one of the REM sleep-modulating structures, is postulated to have a potent antiepileptogenic role. We asked if patients with sleep-predominant seizures (SPS) show volume changes in the region of the PPN compared to those with seizures occurring during awake state only (nSPS). The volume of the PPN region was assessed in patients with SPS, those with nSPS, and healthy volunteers, through voxel-based morphometry and automated, nonbiased region of interest (ROI) analysis of T1 magnetic resonance (MR) images. The volume of PPN region was statistically smaller in patients with SPS (n = 33) than in those with nSPS (n = 40) and healthy controls (n = 30) after controlling for covariates. These results suggest that a structural change in the PPN may be associated with sleep-predominant timing of seizure occurrence. Our findings might help understand the intervening pathomechanism that lies between the human sleep-wake cycle and epilepsy.

The Pivotal Role of the Parieto-Occipital Lobe in Card Game-Induced Reflex Epilepsy: A Voxel-Based Morphometry Study.

BACKGROUND: The pathogenesis of card game-induced reflex epilepsy has not been determined so far. The aim of this study was to evaluate structural abnormalities using voxel-based morphometry (VBM) analysis, which may give some clue about the pathogenesis in card game-induced reflex epilepsy. METHODS: The 3 subjects were diagnosed with card game-induced reflex epilepsy. Evaluation involved a structured interview to obtain clinical information and brain MRI. In VBM analysis, Statistical Parametric Mapping 8 running on the MATLAB platform was employed to analyze the structural differences between patients with card game-induced reflex epilepsy and age- and sex-matched control subjects. RESULTS: The results of VBM analysis revealed that patients with card game-induced reflex epilepsy had significantly increased gray matter volume in the right occipital and parietal lobe. However, there were no structures with decreased gray matter volume in patients with card game-induced reflex epilepsy compared with control subjects. In addition, we found that the patients with card game-induced reflex epilepsy had onset of seizures in adulthood rather than in adolescence, and all of the patients were men. CONCLUSIONS: The parieto-occipital lobes might be partially involved in the neuronal network responsible for card game-induced reflex epilepsy.

Research priorities in epilepsy for the Asia-Oceanian region.

The Asia-Oceanian region is the most populous region in the world. Although there has been substantial economic development and improvement in health services in recent years, epilepsy remains generally an underrecognized and understudied condition. To help promote research in the region, the Commission on Asian and Oceanian Affairs (CAOA) of the International League Against Epilepsy (ILAE) appointed the Research Task Force (RTF) to facilitate the development of research priorities for the region. Research that focuses on issues that are unique or of particular importance in the Asia-Oceanian region is encouraged, and that captures the impact of the dynamic socioeconomic changes taking place in the region is emphasized. Based on these considerations, we propose research "dimensions" as priorities within the Asia-Oceanian region. These are studies (1) that would lead to fuller appreciation of the health burden of epilepsy, particularly the treatment gap; (2) that would lead to better understanding of the causes of epilepsy; (3) that would alleviate the psychosocial consequences of epilepsy; (4) that would develop better therapies and improved therapeutic outcomes; and (5) that would improve the research infrastructure.

Association of knowledge about epilepsy with mood and self-efficacy in Korean people with epilepsy.

PURPOSE: We determined the level of knowledge about epilepsy in Korean people with epilepsy (PWE) and evaluated whether this is associated with self-efficacy, perceived stigma, anxiety, and depressive mood in these patients. METHODS: This was a cross-sectional multicenter study. A total of 530 PWE participated from 31 secondary or tertiary hospitals in Korea. Knowledge about epilepsy was assessed using 34 medical items (EKP-M) of the Epilepsy Knowledge Profile-General. Additional questionnaires included the Epilepsy Self-Efficacy Scale (ESES), Stigma Scale, and Hospital Anxiety and Depression Scale (HADS). Multiple linear regression analyses were used. RESULTS: The mean EKP-M score was 22.2 (SD: 4.1). By univariate analyses, the EKP-M was related to ESES (r=0.220, p<0.001) and HADS-D (r=-0.154, p<0.001) scores but not to the Stigma Scale or HADS-A. By linear regression analyses, after adjusting for the confounding variables, the higher EKP-M scores were independently related to both higher ESES (p<0.001) and lower HADS-D scores (p<0.05). CONCLUSION: Korean PWE have a relatively low level of knowledge about their condition. Knowledge about epilepsy is associated with a high level of self-efficacy and less depressive symptoms in affected individuals.

The effect of recurrent seizures on cognitive, behavioral, and quality-of-life outcomes after 12 months of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy.

PURPOSE: The purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy. METHODS: Seizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist-90 (SCL-90), and the Quality of Life in Epilepsy-31 (QOLIE-31) were administered at baseline and after 48 weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model. RESULTS: A group-by-time interaction was identified for the total QOLIE-31 score (p<0.05) and score on two QOLIE-31 subscales (social function: p<0.001 and seizure worry: p<0.001), with a significant improvement over time only present in the SF group (all p<0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p<0.01) and number of recognition hits on the California Verbal Learning Test (p<0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48 weeks (p<0.01). There was no significant group-by-time interaction for any dimension of the SCL-90. CONCLUSION: Recurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy.

Changing name of epilepsy in Korea; cerebroelectric disorder (noi-jeon-jeung,ë‡Œì „ì¦,): my epilepsy story.

Public misconception of epilepsy may lead to significant stigma to the disease itself, thereby causing impaired quality of life in people with epilepsy. Traditionally, epilepsy has been considered to be the consequence of evanescent spiritual forces, and even demonic possession (in many countries). The names of epilepsy in some East Asian countries originated from China, and include madness in their meaning. We recently changed the Korean name of epilepsy, gan-jil (간질, : a crazy, convulsive disease having meaning similar to ), to a neutral and scientifically explainable name: noi-jeon-jeung (뇌전증; ; cerebroelectric disorder). We expect that changing the stigmatized name of epilepsy to a neutral and scientific term with the meaning of cerebroelectric disorder will reduce the social stigma by understanding of epilepsy as one of the neurologic disorders.

Spectrum of Ictal-Interictal Continuum: The Significance of 2HELPS2B Score and Background Suppression.

PURPOSE: The aims of this study were to identify (1) the spectrum of ictal-interictal continuum (IIC) using the two dimensions of 2HELPS2B score and background suppression and (2) the response to subsequent anti-seizure drugs depends on the spectrum of IIC. METHODS: The study prospectively enrolled 62 patients with IIC on EEG. The diagnosis of nonconvulsive status epilepticus was attempted with Salzburg criteria as well as clinical and neuroimaging data. IICs were dichotomized into patients with nonconvulsive status epilepticus and coma-IIC. The 2HELPS2B score was evaluated as the original proposal. The suppression ratio was analyzed with Persyst software. RESULTS: Forty-seven cases (75.8%) were nonconvulsive status epilepticus-IIC and 15 cases (24.2%) were coma-IIC. Multivariate analysis revealed that the 2HELPS2B score was the only significant variable dichotomizing the spectrum of IIC (odds ratio, 3.0; 95% confidence interval, 1.06-8.6; P = 0.03 for nonconvulsive status epilepticus-IIC). In addition, the suppression ratio was significantly negatively correlated with 2HELPS2B scores (Spearman coefficient = -0.37, P = 0.004 for left hemisphere and Spearman coefficient = -0.3, P = 0.02 for right hemisphere). Furthermore, patients with higher 2HELPS2B score (74% [14/19] in ≥2 points vs. 44% [14/32] in <2 points, P = 0.03 by χ 2 test) and lower suppression ratio (62% [23/37] in ≤2.18 vs. 35% [6/17] in >2.18, P = 0.06 by χ 2 test) seemed to be more responsive to subsequent anti-seizure drug. CONCLUSIONS: The 2HELPS2B score and background suppression can be used to distinguish the spectrum of IIC and thereby predict the response to subsequent anti-seizure drug.

Minimally Invasive Skin Transcriptome Extraction Using a Dermal Biomarker Patch.

INTRODUCTION: Advances in the scientific understanding of the skin and characteristic genomic dermal signatures continue to develop rapidly. Nonetheless, skin diagnosis remains predicated on a subjective visual examination, frequently followed by biopsy and histology. These procedures often are not sufficiently sensitive, and in the case of many inflammatory diseases, biopsies are not justified, creating a situation where high-quality samples can be difficult to obtain. The wealth of molecular information available and the pace at which new data are acquired suggest that methods for minimally invasive biomarker collection could dramatically alter our understanding of skin disease and positively impact treatment paradigms. METHODS: A chemical method was optimized to covalently modify custom dermal patches with single-stranded DNA that could bind to messenger RNA. These patches were applied to ex vivo skin samples and penetration evaluated by histological methods. Patches were then applied to both the skin of normal human subjects (lower arm) as well as lesional skin of psoriasis patients, and the transcriptome captured (N = 7; 33 unique samples). Standard RNA-Seq processing was performed to assess the gene detection rate and assessments made of the reproducibility of the extraction procedure as well as the overlap with matched punch biopsy samples from the same patient. RESULTS: We have developed a dermal biomarker patch (DBP) designed to be minimally invasive and extract the dermal transcriptome. Using this platform, we have demonstrated successful molecular analysis from healthy human skin and psoriatic lesions, replicating the molecular information captured with punch biopsy. CONCLUSION: This DBP enables an unprecedented ability to monitor the molecular "fingerprint" of the skin over time or with various interventions, and generate previously inaccessible rich datasets. Furthermore, use of the DBP could be favored by patients relative to biopsy by limiting pain resulting from biopsy procedures. Given the large dynamic range observed in psoriatic skin, analysis of complex phenotypes is now possible, and the power of machine-learning methods can be brought to bear on dermatologic disease.

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy.

PURPOSE: To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy. METHODS: Thirty-six women on long-term (at least 1 year) topiramate monotherapy were compared with 36 women taking carbamazepine, 32 women taking valproate, and 36 age- and sex-matched controls. Subjects completed bone mineral density (BMD) studies. Serum was analyzed for indices of bone metabolism. KEY FINDINGS: BMD Z-scores, and serum 25-hydroxyvitamin D and 1alpha,25-dihydroxyvitamin D(3) concentrations did not differ among the groups. Serum calcium concentrations were significantly lower in patients receiving topiramate than in those receiving valproate, and in patients receiving carbamazepine than in those receiving valproate and controls. Patients taking topiramate had lower levels of parathyroid hormone compared with controls and those taking carbamazepine or valproate. Patients receiving topiramate had higher levels of bone-specific alkaline phosphatase and osteocalcin when compared with controls and higher levels of C-terminal telopeptide of type 1 collagen when compared with those taking carbamazepine or valproate. Patients receiving carbamazepine had higher levels of bone-specific alkaline phosphatase compared with controls and those receiving valproate. Serum bicarbonate concentrations were significantly lower in patients receiving topiramate than in the other groups. SIGNIFICANCE: Our results demonstrate that use of topiramate is associated with lower parathyroid hormone and bicarbonate concentrations along with mild hypocalcemia and increased bone turnover, which suggests that topiramate may have long-term effects on bone.

Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II.

Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1, 2-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cgamma1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease.