Nervous System-related Symptoms Research Articles

A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms.

this prospective observational study aims to assess serum levels of glial fibrillary acidic protein (GFAP), s100b, and total Tau in long-COVID patients, exploring correlations with symptoms, cognitive decline, mental health, and quality of life. Long-COVID patients visiting our outpatient clinic (February 2021-December 2022) were screened alongside age- and sex-matched controls. GFAP, s100b, and total Tau in serum were measured with ELISA. Cognitive function, depression, anxiety, post-traumatic stress disorder, and quality of life were evaluated using MoCA, HADS (depression and anxiety), IES-R, and SF-36, respectively. Sixty-five long-COVID patients and 20 controls were included. GFAP levels were significantly higher in long-COVID patients (p = 0.031), though not correlating with the presence of long-COVID symptoms. S100b and total Tau showed no significant differences between patients and controls. Nervous system-related symptoms were reported in 47% of patients. High rates of cognitive decline (65.9%), depression (32.2%), anxiety (47.5%), and post-traumatic stress disorder (44.1%) were observed. Over 80% of the study population scored below normative cutoffs for SF-36, indicating a significant impact on quality of life. in this long-COVID cohort with substantial psychological and cognitive symptoms, GFAP levels were elevated compared to controls, though not correlating with the presence of long-COVID symptoms.

Bamboo leaf: A review of traditional medicinal property, phytochemistry, pharmacology, and purification technology.

Bamboos are perennial evergreen plants that belong to the subfamily Bambusoideae of the true grass family Poaceae, with more than thousands of species distributed around the world. They are used as a traditional medicine with demonstrated effects of anti-oxidation, free radical scavenging, anti-inflammatory, liver protection and ameliorating cognitive deficits. Bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic and nervous system diseases. This review aims to provide up-to-date information on the traditional medicinal properties, phytochemistry, pharmacology, and purification technologies of bamboo leaf. Relevant information on bamboo leaf was obtained by an online search of worldwide accepted scientific databases (Web of Science, ScienceDirect, Elsevier, SpringerLink, ACS Publications, Wiley Online Library and CNKI). More than 100 chemical compounds, including flavonoids and flavonoid glycosides, volatile components, phenolic acids, polysaccharide, coenzyme Q10, phenylpropanoid and amino acids have been reported to be present. These compounds were usually extracted by column chromatography and membrane separation technologies. Preparative high performance liquid chromatography (PHPLC), high-speed counter-current chromatography (HSCCC), simulated moving bed chromatography (SMB) and dynamic axial compression chromatography (DAC) were the advanced separation technologies have been used to isolate C-glycosides from bamboo leaf flavonoid, the main bioactive ingredient of bamboo leaf. Currently, bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic, hepatic diseases and nervous system related symptoms, which are attributed to the presence of bioactive components of bamboo leaf. Phytochemical and pharmacological analyses of bamboo leaf have been revealed in recent studies. However, most of the pharmacological studies on bamboo leaf have focused on bamboo leaf flavonoids. Further studies need to pay more attention to other phytochemical components of bamboo leaf. In addition, there is lack of sufficient clinical data and toxicity studies on bamboo leaf. Therefore, more clinical and toxicity researches on this plant and constituents are recommended.

Central nervous system disorders in HIV-infected individuals using distinct antiretroviral drugs.

Neuropsychiatric disorders and central nervous system-related symptoms are very common in people with HIV and can have a very negative impact on their quality of life and worsen the prognosis of the disease. These disorders are multifactorial in origin, but may be triggered or worsened by the use of certain antiretroviral treatments. This paper reviews the epidemiology of neuropsychiatric disorders and symptoms in people with HIV, the recommendations and tools available for their early assessment, as well as the neurotoxicity of the main families of antiretroviral (ARV) drugs. It is important to focus on improvement towards the detection of these disorders during the first evaluation or patient follow-up, aimed at improving quality of life. Because of the central nervous system neurotoxicity profile of different antiretroviral drugs, proactive assessment of neuropsychiatric disorders and symptoms prior to treatment start and during follow-up is necessary.

Autonomic nervous system dysfunction in Prader-Willi syndrome.

Prader-Willi syndrome is a complex neurodevelopmental genetic disorder due to lack of paternal expression of critical imprinted genes in the 15q11.2-q13.1 chromosomal region, generally from a paternal deletion. Predominant features include infantile hypotonia, a poor suck with failure to thrive, craniofacial features, and developmental and behavioral problems including self-injury and childhood onset of obesity. In addition to severe obesity, patients with PWS present with other symptoms of autonomic nervous system dysfunction. We examined the features seen in Prader-Willi syndrome and searched the literature for evidence of autonomic nervous system involvement in this rare obesity-related disorder and illustrative findings possibly due to autonomic nervous system dysfunction. Additionally, we reviewed the literature in relation to childhood obesity syndromes and compared those syndromes to the syndromic obesity found in Prader-Willi syndrome. We report autonomic nervous system-related symptoms associated with childhood obesity impacting features seen in Prader-Willi syndrome and possibly other obesity-related genetic syndromes. We compiled evidence of both an autonomic route for the obesity seen in PWS and other autonomic nervous system-related dysfunctions. These include decreased salvation, sleep disordered breathing, increased pain and thermal threshold instability, delayed gastric emptying, altered blood pressure readings, and pupillary constriction responses as evidence of autonomic nervous system involvement. We summarized and illustrated findings of autonomic nervous system dysfunction in Prader-Willi syndrome and other obesity-related syndromes and genetic factors that may play a causative role in development.

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults.

Cenobamate (CNB) is the latest antiseizure medication (ASM) authorized for the treatment of focal-onset seizures in adults. Although the precise mechanism of action of CNB is not yet fully understood, this drug inhibits the persistent, rather than transient, voltage-gated sodium channel currents and is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, differently from benzodiazepines. CNB has a non-linear pharmacokinetic with a terminal half-life range of about 50/60 hours within the therapeutic dose range, which allows once daily administration. Cenobamate inhibits cytochrome P450 (CYP) 2C19 and induces CYP3A4 and 2B6, and hence can potentially interact with ASMs (eg, phenytoin, carbamazepine and clobazam) and no-ASMs drugs. In two randomized, double-blind, placebo-controlled trials in patients with focal epilepsies, CNB has shown a particularly good efficacy with a rate of seizure freedom of about 20% during the maintenance period in participants treated with the dose of 400 mg/day. The most common treatment-emergent adverse effects include central nervous system-related symptoms, like dizziness, diplopia, somnolence, and gait disturbances. Safety issues of particular interest are severe skin reactions (drug reaction with eosinophilia and systemic symptoms) and QT shortening, which contraindicates its use in subjects with familial short QT syndrome or in combination with other QT-shortening drugs. The recommended starting dose is 12.5 mg/day, which can be gradually titrated to the target dose (200 mg/day) and further increased up to 400 mg/day. There are several aspects of CNB that need to be still addressed, including the long-term efficacy and the efficacy in patients with generalized seizures. Ongoing studies will clarify these issues. The clinical relevance of the peculiar pharmacokinetics and the pattern of drug–drug interactions also require further investigation.

OTHR-05. Diagnosis and Treatment of Solitary Pituitary Metastatic Cancer: A Case Series

ObjectiveMetastatic pituitary carcinoma accounted for only 1% of pituitary lesions.MethodsPatients with isolated pituitary metastatic carcinoma admitted to our hospital from 2014 to 2018 were retrospectively collected, clinical features and prognosis were analyzed.ResultsA total of 5 patients (4 males and 1 female) with a median age of 48 years (21 to 66 years) were included, all with single intracranial pituitary nodules as the initial clinical presentation. The related symptoms were visual impairment (5/5 cases), hypopituitarism (5/5 cases), visual field defect (5/5 cases), headache (4/5 cases), hypothyroidism (4/5 cases), diabetes insipidus (2/5 cases). All the 5 patients received surgical resection (total or partial resection) of tumors in the sellar region via nasal sphenoidal approach. Postoperative pathology confirmed that 4 cases were metastatic adenocarcinoma and 1 case was metastatic squamous carcinoma. Further imaging examinations, such as CT or whole-body PET/CT, confirmed that the primary lesions of all the 5 patients were from the lung. Gene testing indicated that 3 of the 4 adenocarcinoma patients were EGFR mutation positive and 1 of the 4 adenocarcinoma patients was ROS1 mutation positive. Patients received radiotherapy (5/5 cases), targeted therapy (4/5 cases), or chemotherapy (1/5 cases) after surgery. Survival follow-up to May 2019 showed that 4 patients had died, with a survival of 2, August, 28, and 30 months, respectively, and 1 patient was still alive with a survival of 4 months.ConclusionThe first clinical manifestation of isolated pituitary metastatic carcinoma is nervous system related symptoms, which is easily misdiagnosed. The most of the primary lesions are from lung, especially lung adenocarcinoma with positive driver gene. Surgery, radiotherapy combined with targeted therapy or chemotherapy can provide survival benefits for patients with pituitary metastatic carcinoma.

Pharmacology of Cenobamate: Mechanism of Action, Pharmacokinetics, Drug-Drug Interactions and Tolerability.

Cenobamate is one of the latest antiseizure medications (ASMs) developed for the treatment of focal onset seizures in adult patients. The recommended starting dose is 12.5mg/day, titrated gradually to the target daily dose of 200 mg, which may be increased to a maximum of 400 mg/day based on clinical response. Although the high rate of seizure freedom observed in randomized, placebo-controlled clinical trials has resulted in exciting expectations, further clinical studies are needed to better define its clinical profile. Cenobamate is characterized by a peculiar pharmacology regarding both pharmacodynamics and pharmacokinetics. The mechanism of action has only partly been described, with the drug acting on voltage-gated sodium channels through a pronounced action on persistent rather than transient currents. Cenobamate also acts as a positive allosteric modulator of GABAA receptors independently from the benzodiazepine binding site. The bioavailability of cenobamate is not influenced by other drugs, except phenytoin; it can inhibit cytochrome P450 (CYP)2C19 and induce CYP3A4 and 2B6, and hence can potentially interact with many drugs (e.g. dose adjustments may be required for lamotrigine, carbamazepine and clobazam). The pharmacokinetics of cenobamate are not linear and dosage increases imply a disproportional increase in plasma levels, particularly at doses higher than 300mg. The most common and dose-related adverse effects associated with cenobamate include central nervous system-related symptoms, mainly somnolence, dizziness, diplopia, and disturbances in gait and coordination. A somewhat higher incidence of adverse events has been observed in patients concomitantly treated with sodium channel blockers. The most relevant safety issues are currently represented by the risk of severe skin reactions (apparently avoidable by a slow titration) and QT shortening (the drug is contraindicated in patients with familial short QT syndrome or taking QT-shortening drugs). Overall, cenobamate is a promising ASM with an intriguing and not fully understood mechanism of action; pharmacokinetic issues need to be considered in clinical practice.

Nonclinical safety evaluation of pabinafusp alfa, an anti-human transferrin receptor antibody and iduronate-2-sulfatase fusion protein, for the treatment of neuronopathic mucopolysaccharidosis type II

Pabinafusp alfa is a fusion protein comprising a humanized anti-human transferrin receptor (TfR) antibody and human iduronate-2-sulfatase. It was developed as a novel modality to target central nervous system-related symptoms observed in patients with mucopolysaccharidosis type II (MPS II, also known as Hunter syndrome). As the fusion protein contains an entire IgG1 molecule that binds TfR, there may be specific safety concerns, such as unexpected cellular toxicity due to its effector functions or its ability to inhibit iron metabolism, in addition to general safety concerns. Here, we present the comprehensive results of a nonclinical safety assessment of pabinafusp alfa. Pabinafusp alfa did not exhibit effector functions, as assessed by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity studies in TfR-expressing hematopoietic cells. Repeat-dose toxicity studies in cynomolgus monkeys showed that pabinafusp alfa did not induce any significant toxicological changes at doses up to 30 mg/kg/week upon intravenous administration for up to 26 weeks. Interaction of transferrin with TfR was not inhibited by pabinafusp alfa, suggesting that the effect of pabinafusp alfa on the physiological iron transport system is minimal, which was confirmed by toxicity studies in cynomolgus monkeys. These findings suggest that pabinafusp alfa is expected to be safe for long-term use in individuals with MPS II.

Cryptococcus transmission through solid organ transplantation in the United States: A report from the Ad Hoc Disease Transmission Advisory Committee.

Cryptococcus species can cause serious life-threatening infection in solid organ transplant recipients by reactivation of prior infection, posttransplant de novo infection, or donor transmission from the transplanted organ. Although previously reported in the literature, the extent of donor-derived cryptococcosis in the United States has not been documented. We analyzed potential donor-derived Cryptococcus transmission events reported to the Organ Procurement and Transplantation Network (OPTN) for investigation by the Ad Hoc Disease Transmission Advisory Committee (DTAC). All reports between 2009 and 2019 in which transmission to recipients was designated proven or probable, or determined to be averted due to implementation of prophylaxis (intervention without disease transmission-"IWDT") were included. During 2009-2019, 58 reports of potential donor-derived cryptococcosis were submitted to DTAC. Among these reports, 12 donors were determined to have resulted in proven or probable transmission to 23/34 (67.6%) recipients. Most of these donors (10/12 [83%]) exhibited central nervous system-related symptoms prior to death and 5/23 (22%) infected recipients died. For 11 different donors, prophylaxis, most often with fluconazole, was administered to 23/35 (65.7%) recipients. Clinicians should maintain awareness of donor-derived cryptococcosis and consider prompt prophylaxis or treatment followed by reporting to OPTN for further investigation.

Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts

Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (Systemic Exertion Intolerance Disorder), is a disabling and often long-lasting disease that can drastically impair quality of life and physical/social functioning of the patients. Underlying pathological mechanisms are to a large extent unknown, but the presence of autoantibodies, cytokine pattern deviations and the presentation of cognitive and autonomic nervous system related symptoms provide evidence for ME being an immunological disorder with elements of autoimmunity. Increased levels of autoantibodies binding to adrenergic and muscarinic receptors in ME-patients have been reported. It is hypothesized that these autoantibodies have pathological significance and contribute to the ME-specific symptoms, however, these observations need to be validated.This study was designed to investigate potential differences in adrenergic and muscarinic receptor autoantibody levels in plasma and cerebrospinal fluid (CSF) samples between ME patients and gender and age-matched healthy controls, and to correlate the autoantibody levels to disease severity.We collected bodyfluids and health-related questionnaires from two Swedish ME cohorts, plasma and CSF from one of the cohorts (n ​= ​24), only plasma from the second cohort (n ​= ​24) together with plasma samples (n ​= ​24) and CSF (n ​= ​6) from healthy controls.All samples were analysed for IgG autoantibodies directed against Alpha- (α1, α2) and Beta- (β1-3) adrenergic receptors and Muscarinic (M) 1–5 acetylcholine receptors using an ELISA technique. The questionnaires were used as measures of disease severity.Significant increases in autoantibody levels in ME patients compared to controls were found for M3 and M4 -receptors in both cohorts and β1, β2, M3 and M4-receptors in one cohort. No significant correlations were found between autoantibody levels and disease severity. No significant levels of autoantibodies were detected in the CSF samples. These findings support previous findings that there exists a general pattern of increased antibody levels to adrenergic and muscarinic receptors within the ME patient group. However, the role of increased adrenergic and muscarinic receptor autoantibodies in the pathogenesis of ME is still uncertain and further research is needed to evaluate the clinical significance of these findings.

Protective effects of mirtazapine in mice lacking the Mbnl2 gene in forebrain glutamatergic neurons: Relevance for myotonic dystrophy 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and wasting and by important central nervous system-related symptoms including impairments in executive functions, spatial abilities and increased anxiety and depression. The Mbnl2 gene has been implicated in several phenotypes consistent with DM1 neuropathology. In this study, we developed a tissue-specific knockout mouse model lacking the Mbnl2 gene in forebrain glutamatergic neurons to examine its specific contribution to the neurobiological perturbations related to DM1. We found that these mice exhibit long-term cognitive deficits and a depressive-like state associated with neuronal loss, increased microglia and decreased neurogenesis, specifically in the dentate gyrus (DG). Chronic treatment with the atypical antidepressant mirtazapine (3 and 10 mg/kg) for 21 days rescued these behavioral alterations, reduced inflammatory microglial overexpression, and reversed neuronal loss in the DG. We also show that mirtazapine re-established 5-HT1A and histaminergic H1 receptor gene expression in the hippocampus. Finally, metabolomics studies indicated that mirtazapine increased serotonin, noradrenaline, gamma-aminobutyric acid and adenosine production. These data suggest that loss of Mbnl2 gene in the glutamatergic neurons of hippocampus and cortex may underlie the most relevant DM1 neurobiological and behavioral features, and provide evidence that mirtazapine could be a novel potential candidate to alleviate these debilitating symptoms in DM1 patients.

Methylmalonic and propionic acidemia among hospitalized pediatric patients: a nationwide report

BackgroundMethylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China.MethodsThe data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data.ResultsAmong all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013 (0.76% for MMA; 0.13% for PA) to 2017 (1.61% for MMA; 0.32% for PA). For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high (RMB 7388.53 for MMA; RMB 4999.66 for PA). Moreover, most patients hospitalized in tertiary class A hospitals (MMA: 80.96%, PA: 76.21%); and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization.ConclusionsThe study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed.

CMET-10. INTRACRANIAL SOLITARY PITUITARY METASTASIS: THE IMPLICATIONS FROM FIVE CASES

Abstract BACKGROUND Pituitary gland metastasis is a rare disease which represents only 1% of pituitary gland lesions. Intracranial solitary pituitary metastasis tends to be misdiagnosed as pituitary adenoma, resulting in a delayed anti-tumor treatment. METHODS Five cases of patients with pituitary gland metastasis recorded between 2014 and 2018 in our hospital were investigated with reference to patient demographics, symptoms at presentation, radiological and histological findings, management and outcomes. RESULTS Five patients (4 male and 1 female) were included and the median age was 48 years (range: 21 to 66). In those five cases, central nervous system related symptoms were the first sign of malignancy, including visual loss (5 in 5 patients), visual field defects (5 in 5 patients), apituitarism (5 in 5 patients), headache (4 in 5 patients), hypothroidism (4 in 5 patients) and diabetes insipidus (2 in 5 patients). All patients received total or partial hypophysectomy and pathologically revealed metastatic adenocarcinoma in 4 patients and metastatic squamous carcinoma in 1 patient. Further examinations by Computed Tomography (CT) or Positron Emission Computed Tomography (PET) indicated lung as primary site in five cases. EGFR mutation and ROS1 fusion were found in 3 and 1 adenocarcinoma patient, respectively, through gene detection of tissue. Postoperative radiotherapy (5 patients), target therapy (4 patients) and chemotherapy (1 patient) were given as subsequent treatment. During the follow-up, four patients died and the overall survival was 2, 8, 28 and 30 months, respectively. CONCLUSION We found that pituitary symptoms usually presented as the first sign of malignancy in intracranial solitary pituitary metastasis. Lung is the most frequently primary site, particularly in adenocarcinoma with driver gene mutation. Patients may benefit from multidiscipline treatment, including resection of pituitary metastasis combined with radiotherapy and targeted therapy.

Recognizing Central Nervous System Involvement as a Progressive Feature of Microscopic Polyangiitis: A Diagnostic Dilemma

Microscopic polyangiitis is an idiopathic autoimmune disease characterized by systemic vasculitis predominantly of small-caliber blood vessels with antineutrophilic cytoplasmic antibodies (ANCA), and it can have a variable presentation. 1 Chung S.A. Seo P. Microscopic polyangiitis. Rheum Dis Clin N Am. 2010; 36: 545-558 Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar We present the case of a 57-year-old male smoker with central nervous system-related symptoms of left facial droop, dysarthria, and worsening left upper-extremity weakness and numbness due to multiple strokes as a manifestation of microscopic polyangiitis.

Intravascular large cell lymphoma mimicking central nervous system vasculitis in a patient with rheumatoid arthritis (RCD code: VI-2C.2)

Increased incidence of lymphomas in patients with rheumatoid arthritis has been reported and may be associated with several factors, including genetic factors, chronic inflammation, and immunosuppressive treatment. Intravascular large cell lymphoma (ILCL) is a rare subtype of large cell lymphoma with undetectable lymphoma cells in peripheral blood and without any extravascular localisation. Diag- nosis is often delayed because bone marrow, spleen, and cerebrovascular fluid may not be involved and there are no specific laboratory studies for intravascular large cell lymphoma. We report the case of a 63-year-old woman with a 10-year history of seropositive rheumatoid arthritis and intravascular large cell lymphoma recognised at autopsy. The patient presented with progressive central nervous system-related symptoms mimicking vasculitis without lymphadenopathy or bone marrow involvement. Malignant lymphoproliferative disorders should be considered in RA patients with varying clinical presentation, even in the absence of lymphadenopathy and bone marrow involvement. JRCD 2018; 4 (1): 15-17.

Symptoms of Nervous System Related Disorders Among Workers Exposed to Occupational Noise and Vibration in Korea.

The aim of this study was to determine the relationship between vibration and noise exposure in the workplace and certain nervous system related symptoms (NSRS) among Korean workers. Using data from the fourth Korean Working Conditions Survey, we investigated the influence of vibration and noise with three categories; none, mild, and severe, on sleep disturbance, overall fatigue, and headache/eye strain using logistic regression analysis with stratification by personal protective equipment (PPE) wearing status. Severe noise/vibration exposure was associated in a dose-response fashion with NSRS; the odds ratios (ORs) for sleep disturbance, headache/eyestrain, and overall fatigue were 1.48/1.06, 1.46/1.26, and 1.56/1.28 for severe and mild noise/vibration exposure, respectively, compared with no exposure. Workers who did not wear PPEs were the most affected. Occupational exposures to vibration and noise are associated with NSRS. Additional longitudinal studies and tightened education and safety measures are warranted.

Korean Red Ginseng exhibits no significant adverse effect on disease activity in patients with rheumatoid arthritis: a randomized, double-blind, crossover study

BackgroundPanax ginseng is a well-known immune modulator, and there is concern that its immune-enhancing effects may negatively affect patients with rheumatoid arthritis (RA) by worsening symptoms or increasing the risk of adverse effects from other drugs. In this randomized, crossover clinical trial, we evaluated the impact of Korean Red Ginseng (KRG) on disease activity and safety in RA patients. MethodsA total of 80 female RA patients were randomly assigned to either the KRG (2 g/d, n=40) treatment or placebo (n=40) groups for 8 wk, followed by crossover to the other treatment group for an additional 8 wk. The primary outcome was the disease flare rate, defined as worsening disease activity according to the disease activity score 28 joints-erythrocyte sedimentation rate (DAS28-ESR). The secondary outcomes were development of adverse events (AEs) and patient reported outcomes. Outcomes were evaluated at baseline and 8 wk and 16 wk. The outcomes were compared using the Chi-square test. ResultsOf the 80 patients, 70 completed the full study. Their mean age was 51.9 yr, and most exhibited low disease activity (mean DAS28-ESR 3.5±1.0) at enrollment. After intervention, the flare rate was 3.7% in each group. During KRG treatment, 10 AEs were reported, while five AEs were developed with placebo; however, this difference was not statistically significant (p=0.16). Gastrointestinal- and nervous system-related symptoms were frequent in the KRG group. ConclusionKRG is not significantly associated with either disease flare rate or the rate of AE development in RA patients.

Posterior reversible encephalopathy syndrome following pembrolizumab therapy for relapsed Hodgkin’s lymphoma

Posterior reversible encephalopathy syndrome (PRES) is characterized by a group of central nervous system related symptoms. Diagnosis is usually made by computed tomography or magnetic resonance imaging. Common causes can be arterial hypertension, sepsis, autoimmune disorders, and medications. We report PRES in a relapsed Hodgkin's Lymphoma patient after a dose of pembrolizumab.

Tu2006 Internet-Delivered Cognitive Behavior Therapy for Adolescents With Functional Gastrointestinal Disorders: A Pilot Study

the association with foregut symptoms. Methods: We conducted a retrospective review of the medical notes and electronic patient records for all children diagnosed with JHS (Beighton score >4/9) referred to the syncope service based at Hammersmith Hospital. The study period was June 2011 to October 2013. Cardiovascular autonomic function was evaluated using the tilt table test. Results: A total of 53 children were recruited with a median age range of 15.2 yrs (range 8.1yrs-18.7 yrs). The gender distribution was 28 females (53%) and 25 males (47%). All patients had autonomic nervous system-related symptoms including postural dizziness or syncope (53%), palpitations (40%), migraine (25%) and chest pain (19%). Of the 53 JHS patients with autonomic symptoms, 48 (91%) patients had GI-related symptoms. 45 (85%) of these patients had confirmed cardiovascular autonomic dysfunction on tilt testing. All these patients also complained of foregut symptoms, predominantly nausea and bloating. Summary: Foregut dysfunction was a co-morbid presentation in all JHS patients with cardiovascular dysautonomia. Conclusion: Children with JHS presenting with foregut symptoms are likely to have associated cardiovascular autonomic dysfunction. Recognition of these symptoms by paediatricians is important as formal evaluation and treatment of the dysautonomia may improve the quality of life for these patients. Further studies are required to evaluate the objective improvement of GI symptoms following treatment for dysautonomia.

홍화 지상부 추출물의 전뇌허혈에 대한 신경보호 효과

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 ㎎/㎏ body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) (55.2 ± 9.4 µmol mg -1 ) and significant improvement of activities of glutathione (GSH) (27.2 ± 5.0 µmol mg -1 ) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.