Substance P (SP) is one of the most abundant peptides in the central nervous system and has been implicated in a variety of physiological and pathophysiological processes including stress regulation, as well as affective and anxiety-related behaviour. Consistent with these functions, SP and its preferred neurokinin 1 (NK1) receptor has been found within brain areas known to be involved in the regulation of stress and anxiety responses. Aversive and stressful stimuli have been shown repeatedly to change SP brain tissue content, as well as NK1 receptor binding. More recently it has been demonstrated that emotional stressors increase SP efflux in specific limbic structures such as amygdala and septum and that the magnitude of this effect depends on the severity of the stressor. Depending on the brain area, an increase in intracerebral SP concentration (mimicked by SP microinjection) produces mainly anxiogenic-like responses in various behavioural tasks. Based on findings that SP transmission is stimulated under stressful or anxiety-provoking situations it was hypothesised that blockade of NK1 receptors may attenuate stress responses and exert anxiolytic-like effects. Preclinical and clinical studies have found evidence in favour of such an assumption. The status of this research is reviewed here.

The role of substance P in stress and anxiety responses

Adverse drug reactions induced by valproic acid

BackgroundRosai-Dorfman disease (RDD) is a rare, nonmalignant clinical entity characterized by a group of clinical symptoms and characteristic pathological features.MethodsArticles that reviewed tumor biology, clinical features, pathology, and treatment for RDD were identified in a search of the literature for the years 1990 to 2014. The results from this body of literature were reviewed and summarized.ResultsPatients with RDD generally present with massive, painless cervical lymphadenopathy, fevers, and elevated inflammatory markers. Extranodal disease is typical, with the most common sites being the skin and the central nervous system. Rarely, the gastrointestinal tract is involved. Immunohistochemistry remains the mainstay of diagnosis with S100 and CD68 positive cells while CD1a will be negative of involved histiocytes. Histologically, the disease shows the classical characteristic finding of emperipolesis. Many patients do not require treatment; however, surgical resection remains the mainstay of tre...

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Rosai-Dorfman Disease: Tumor Biology, Clinical Features, Pathology, and Treatment:

Electroencephalography–functional magnetic resonance imaging (EEG-fMRI) is a noninvasive technique that allows visualizing the brain’s hemodynamic changes associated with epileptic activity. This method utilizes the high temporal resolution of EEG and the high spatial resolution of fMRI to study metabolic activity of the whole brain, simultaneously. EEG-fMRI has become a valuable tool in the presurgical evaluation of patients with pharmacoresistant epilepsy and to study epileptic networks (Zijlmans et al., 2007; Gotman, 2008; Thornton et al., 2010).

Group analyses of EEG-fMRI scans from selected sets of patients demonstrate metabolic changes that may not be apparent in individual patients. For instance, studies of patients with generalized epilepsies show common bilateral activation in cortical regions, thalami, and cerebellum, whereas the caudate nuclei and default mode network (DMN) regions were deactivated (Gotman et al., 2005; Carney et al., 2010; Siniatchkin et al., 2011). The extent of networks involved in focal epileptic activity is much less clear; group analysis of EEG-fMRI has been limited to studies of temporal lobe epilepsy (TLE) and heterogeneous groups of focal epilepsy patients and using 1.5 Tesla scans (Laufs et al., 2007; Kobayashi et al., 2009; Laufs et al., 2011). A group analysis of 19 patients with different focal epileptic syndromes converged to a single activation cluster in the ipsilateral anterior piriform cortex (Laufs et al., 2011).

We report the epileptic networks associated with focal interictal epileptiform discharges (IEDs) using 3T EEG-fMRI. We selected patients with TLE, frontal lobe epilepsy (FLE), and posterior quadrant epilepsy (PQE) and performed group analyses. We describe blood oxygen–level dependent (BOLD) responses of cortical, subcortical, and DMN regions differentially involved in each patient group.

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Widespread epileptic networks in focal epilepsies: EEG-fMRI study

This study aimed to investigate the association between HLA genotypes and antiepileptic drug-induced cutaneous adverse reactions (AEDs-cADRs) among patients with epilepsy in Ningxia Hui Autonomous Region of Northwest China. Fifteen patients with AEDs-cADRs and 30 matched AEDs tolerant controls from anested case-control study were tested the HLA-A, HLA-B, and HLA-DRB1 genotype using the polymerase chain reaction sequence-based typing (PCR-SBT). Significant difference was not observed between AEDs-cADRs and AEDs tolerant groups in terms of HLA-A, HLA-B, and HLA-DRB1 genotype frequencies. Future studies using larger cohorts are needed to verify this observation.

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Association Between HLA Genotype and Cutaneous Adverse Reactions to Antiepileptic Drugs Among Epilepsy Patients in Northwest China.

Rosai-Dorfman disease: a retrospective analysis of 13 cases.

Objective Due to less experience with the cross-reactivity of antiepileptic drugs (AEDs) in Chinese population, we surveyed the rates of cross- reactivity of rash among commonly used AEDs in Chinese patients with epilepsy, particularly between the traditional and the new compounds. Methods We have retrospectively reviewed the medical records concerning all antiepileptic drug treatment in consecutive Chinese patients with epilepsy in our center. The incidence of AED-related rash was determined in 3793 outpatients, taking at least one of the AEDs-carbamazepine (CBZ), valproic acid (VPA), phenytoin (PHT), phenobarbital (PB), clonazepam (CZP), oxcarbazepine (OXC), lamotrigine (LTG), gabapentin (GBP), topiramate (TPM), levetiracetam (LEV) and traditional Chinese medicine (TCM). We have performed telephone interviews among all patients with AEDs-related rash. We described the clinical characteristics of the 18 patients with cross-reactivity involving the AEDs, and the cross- reactivity pattern for CBZ, PHT, OXC, and LTG. Results A total of 3.61% (137/3793) of patients experienced a skin rash to at least one AEDs, of these patients, 73 (53.28%) were female and 64 were males (46.72%). While 18 patients had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT ( n =17), 52.9% had a rash to PHT (abbreviated as CBZ→PHT: 52.9%); of patients who had a rash to PHT and were also prescribed CBZ ( n =13), rate of rash was 69.2% (i.e., PHT→CBZ: 69.2%). Other results: CBZ→LTG: 25% ( n =16); LTG →CBZ: 44.4% ( n =9); CBZ→OXC: 40% ( n =10); OXC→CBZ: 66.7% ( n =6); LTG→PHT: 20% ( n =5); PHT→LTG: 16.7% ( n =6); OXC→LTG: 25% ( n =4); LTG→OXC: 33.3% ( n =3); OXC→PHT: 25% ( n =4); PHT→OXC: 16.7% ( n =6). There was a highly significant mutual risk for cross- reactivity for CBZ and PHT, and OXC, and LTG ( p p =0.01). Conclusion Cross-reactivity rates between certain AEDs are high, especially when involving carbamazepine and phenytoin. There were also too few patients with rash to reach definitely conclusions about possible cross-reactivity. Larger numbers of patients would be needed to assess this and the mechanism. Caution should be exercised when prescribing certain AEDs (especially CBZ and PHT, but also OXC, and LTG).

Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population.

The aim of this study is to assess related risk factors and predict early- and late-onset seizure after first-ever stroke. A total of 2474 consecutive patients with initial stroke in China from 1997 to 2007 were retrospectively investigated, in which, 24 clinical and radiological indexes were used for evaluation. Odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression. A total of 232 (11.1%) of patients developed seizures during a mean follow-up period of 18 months, with 123 experiencing early-onset and 109 late-onset seizure. The independent risk factors for early-onset seizure were large lesion (OR = 9.36), subarachnoid hemorrhage (OR = 5.28), initial hyponatremia (OR = 2.10), and cortical involvement (OR = 1.33). The independent risk factors for late-onset seizure were cortical involvement (OR = 11.84) and large lesion (OR = 1.87). These results demonstrated that the risk factors for early seizure after stroke are large lesion, subarachnoid hemorrhage, and cortical involvement. Surprisingly, hyponatremia also predicts seizure in stroke patients. Cortical involvement is a major risk factor for late-onset seizure after stroke.

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Analysis of Risk Factors for First Seizure after Stroke in Chinese Patients

Antiepileptic drug-induced skin reactions: A retrospective study and analysis in 3793 Chinese patients with epilepsy

Purpose We systematically reviewed studies to provide current evidence on the incidence and risk of skin rash in patients with LTG therapy. Methods PubMed and Scopus databases, up to 15 March 2014 were searched to identify relevant studies. Eligible studies included prospective studies, retrospective studies and postmarketing reports, which included data of skin rash in patients with LTG therapy. Results Forty-one articles met the entry criteria. A total of 4447 patients with LTG therapy from 26 prospective studies, 2977 patients from 8 retrospective studies, and 26,126 patients from 5/7 postmarketing reports were included. The overall incidence of skin rash with LTG therapy was 9.98% (444/4447) from prospective studies, 7.19% (214/2977) from retrospective studies, and 2.09% (547/26,126) from postmarketing reports. A meta-analysis of the risk of skin rash in 21 prospective studies, did not show a significant difference between patients with LTG and other drugs, including placebo, other ADEs or lithium (OR 0.99–2.41). In 6 respective studies, there was a significantly higher OR in patients with LTG compared with those with non-aromatic AEDs. However, there was no significant difference in rash risk between patients with LTG and aromatic AEDs. Conclusions Our study showed that LTG significantly increased the risk of developing a skin rash compared to non-aromatic AEDs. Our results support the need for large prospective population-based studies and clinical trials to determine whether LTG increases the risk of developing a skin rash than compared to other drugs.

Sen-yang Lang

Papers

Rosai-Dorfman disease: a retrospective analysis of 13 cases.

Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population.

Analysis of Risk Factors for First Seizure after Stroke in Chinese Patients

Antiepileptic drug-induced skin reactions: A retrospective study and analysis in 3793 Chinese patients with epilepsy

Risk of a lamotrigine-related skin rash: current meta-analysis and postmarketing cohort analysis.