A diagnostic dilemma between psychosis and post-traumatic stress disorder: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Post-traumatic stress disorder is defined as a mental disorder that arises from the experience of traumatic life events. Research has shown a high incidence of co-morbidity between post-traumatic stress disorder and psychosis.</p> <p>Case presentation</p> <p>We report the case of a 32-year-old black African woman with a history of both post-traumatic stress disorder and psychosis. Two years ago she presented to mental health services with auditory and visual hallucinations, persecutory delusions, suicidal ideation, recurring nightmares, hyper-arousal, and initial and middle insomnia. She was prescribed trifluoperazine (5 mg/day) and began cognitive-behavioral therapy for psychosis. Her psychotic symptoms gradually resolved over a period of three weeks; however, she continues to experience ongoing symptoms of post-traumatic stress disorder. In our case report, we review both the diagnostic and treatment issues regarding post-traumatic stress disorder with psychotic symptoms.</p> <p>Conclusions</p> <p>There are many factors responsible for the symptoms that occur in response to a traumatic event, including cognitive, affective and environmental factors. These factors may predispose both to the development of post-traumatic stress disorder and/or psychotic disorders. The independent diagnosis of post-traumatic stress disorder with psychotic features remains an open issue. A psychological formulation is essential regarding the appropriate treatment in a clinical setting.</p

ER Stress-Inducible Factor CHOP Affects the Expression of Hepcidin by Modulating C/EBPalpha Activity

Endoplasmic reticulum (ER) stress induces a complex network of pathways collectively termed the unfolded protein response (UPR). The clarification of these pathways has linked the UPR to the regulation of several physiological processes. However, its crosstalk with cellular iron metabolism remains unclear, which prompted us to examine whether an UPR affects the expression of relevant iron-related genes. For that purpose, the HepG2 cell line was used as model and the UPR was activated by dithiothreitol (DTT) and homocysteine (Hcys). Here, we report that hepcidin, a liver secreted hormone that shepherds iron homeostasis, exhibits a biphasic pattern of expression following UPR activation: its levels decreased in an early stage and increased with the maintenance of the stress response. Furthermore, we show that immediately after stressing the ER, the stress-inducible transcription factor CHOP depletes C/EBPα protein pool, which may in turn impact on the activation of hepcidin transcription. In the later period of the UPR, CHOP levels decreased progressively, enhancing C/EBPα-binding to the hepcidin promoter. In addition, analysis of ferroportin and ferritin H revealed that the transcript levels of these iron-genes are increased by the UPR signaling pathways. Taken together, our findings suggest that the UPR can have a broad impact on the maintenance of cellular iron homeostasis

Multilayered Mechanism of CD4 Downregulation by HIV-1 Vpu Involving Distinct ER Retention and ERAD Targeting Steps

A key function of the Vpu protein of HIV-1 is the targeting of newly-synthesized CD4 for proteasomal degradation. This function has been proposed to occur by a mechanism that is fundamentally distinct from the cellular ER-associated degradation (ERAD) pathway. However, using a combination of genetic, biochemical and morphological methodologies, we find that CD4 degradation induced by Vpu is dependent on a key component of the ERAD machinery, the VCP-UFD1L-NPL4 complex, as well as on SCFβ-TrCP-dependent ubiquitination of the CD4 cytosolic tail on lysine and serine/threonine residues. When degradation of CD4 is blocked by either inactivation of the VCP-UFD1L-NPL4 complex or prevention of CD4 ubiquitination, Vpu still retains the bulk of CD4 in the ER mainly through transmembrane domain interactions. Addition of a strong ER export signal from the VSV-G protein overrides this retention. Thus, Vpu exerts two distinct activities in the process of downregulating CD4: ER retention followed by targeting to late stages of ERAD. The multiple levels at which Vpu engages these cellular quality control mechanisms underscore the importance of ensuring profound suppression of CD4 to the life cycle of HIV-1

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: Case report

Abstract Background The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial. Case presentation We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment. Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved. Conclusions This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.</p

Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis

The ketogenic diet (KD), containing high levels of fat and low levels of carbohydrates, has been used to treat refractory epilepsy since the 1920s. In the past few decades, there has been more interest in less restrictive KDs such as the modified Atkins diet (MAD). PURPOSE: Our aim was to review all evidence regarding the efficacy and tolerability of the KD and MAD from randomized controlled trials (RCTs) in children and adolescents with refractory epilepsy. METHODS: We reviewed the current literature using Cochrane, EMBASE, and MEDLINE (using PubMed). We implemented predefined criteria regarding dataextraction and study quality. RESULTS: We identified five RCTs that generated seven publications and recruited 472 children and adolescents with refractory epilepsy (≤ 18 years). The primary outcome (seizure frequency reduction (SFR) ≥ 50%) was attained in 35-56.1% of the participants in the intervention group, compared with 6-18.2% in the control group. Our meta-analysis underlined the significant efficacy of the KD compared with the control group: RR = 5.1 (95% CI 3.18-8.21, p < 0.001). Additionally, only two studies mentioned possible biomarkers to objectively evaluate the efficacy. Secondary outcomes, such as seizure severity and quality of life, were studied in three trials, leading to indecisive generalization of these findings. Gastro-intestinal adverse effects were the most prevalent, and no severe adverse effects were reported. CONCLUSION: Despite the heterogeneity between all studies, the beneficial results underline that dietary interventions should be considered for children and adolescents with refractory epilepsy who are not eligible for epilepsy surgery. Future studies should be multi-center and long-term, and evaluate potential biomarkers and adverse effects.status: publishe

Epidemiology of acute flaccid myelitis in children in the Netherlands, 2014 to 2019.

BackgroundAcute flaccid myelitis (AFM) is a polio-like condition affecting mainly children and involving the central nervous system (CNS). AFM has been associated with different non-polio-enteroviruses (EVs), in particular EV-D68 and EV-A71. Reliable incidence rates in European countries are not available.AimTo report AFM incidence in children in the Netherlands and its occurrence relative to EV-D68 and EV-A71 detections.MethodsIn 10 Dutch hospitals, we reviewed electronic health records of patients diagnosed with a clinical syndrome including limb weakness and/or CNS infection and who were < 18 years old when symptoms started. After excluding those with a clear alternative diagnosis to AFM, those without weakness, and removing duplicate records, only patients diagnosed in January 2014-December 2019 were retained and further classified according to current diagnostic criteria. Incidence rates were based on definite and probable AFM cases. Cases' occurrences during the study period were co-examined with laboratory-surveillance detections of EV-D68 and EV-A71.ResultsAmong 143 patients included, eight were classified as definite and three as probable AFM. AFM mean incidence rate was 0.06/100,000 children/year (95% CI: -0.03 to 0.14). All patient samples were negative for EV-A71. Of respiratory samples in seven patients, five were EV-D68 positive. AFM cases clustered in periods with increased EV-D68 and EV-A71 detections.ConclusionsAFM is rare in children in the Netherlands. The temporal coincidence of EV-D68 circulation and AFM and the detection of this virus in several cases' samples support its association with AFM. Increased AFM awareness among clinicians, adequate diagnostics and case registration matter to monitor the incidence