Acute necrotizing encephalopathy.

Influenza virus infection is a rare cause of neurological complications, with acute necrotizing encephalopathy (ANE) being among the deadliest. Due to the low incidence of ANE, literature about its association with influenza B infection is limited. We present the case of a 29-year-old previously healthy man with an imaging and clinical diagnosis of influenza B virus infection and sudden decline in mental status. Magnetic resonance imaging showed multifocal areas of abnormal T2 FLAIR signal and restricted diffusion without significant enhancement, with negative mircobiological studies of cerebrospinal fluid. The patient died despite multiple treatments including an antiviral, steroids, and intravenous immunoglobulin. Due to ANE's more common presentation during childhood, this case report represents one of the few available publications in the adult population.

Increased creativity associated with dopamine agonist therapy: A case report and short review of the literature.

Impulse control disorder (ICD) has been linked to dopamine agonist use in patients with Parkinson's disease. Increased creativity is another cognitive side effect of dopaminergic therapy. While ICD is well recognized in the literature, enhanced creativity as a positive phenomenon is underreported because it does not negatively affect the patients' quality of life. Herein, we report a case of a 49-year-old man with Parkinson's disease who developed enhanced creativity expressed by the acquisition of multiple, new artistic skills with ropinirole treatment. He spent a significant amount of time on painting, carving and axe restoration, selling these artistic products became a source of income. He also reports that these hobbies help him cope with physical limitations caused by Parkinson's disease.

De Novo Myasthenia Gravis Induced by Atezolizumab in a Patient with Urothelial Carcinoma.

The programmed cell death ligand-1 antibody, atezolizumab, is an immune checkpoint inhibitor approved for the treatment of various cancers. Herein, we describe a case of an 87-year-old man with advanced urothelial carcinoma. After surgery, atezolizumab was given. Subsequently, he developed generalized myasthenia gravis (MG) with elevated creatinine kinase and positive anti-striated muscle antibody. Although intravenous immunoglobulin was started, the patient developed cardiac arrhythmia and arrest. Our case not only reported MG as an immune-related adverse event of atezolizumab but also emphasized the significance of the programmed cell death-1 pathway in the pathogenesis of MG.

Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia.

Over the last years, studies on microglia cell function in chronic neuro-inflammation and neuronal necrosis pointed towards an eminent role of these cells in Multiple Sclerosis, Parkinson's and Alzheimer's Disease. It was found, that microglia cell activity can be stimulated towards a pro- or an anti-inflammatory profile, depending on the stimulating signals. Therefore, investigation of receptors expressed by microglia cells and ligands influencing their activation state is of eminent interest. A receptor found to be expressed by microglia cells is the mineralocorticoid receptor. One of its ligands is Aldosterone, a naturally produced steroid hormone of the adrenal cortex, which mainly induces homeostatic and renal effects. We evaluated if the addition of Aldosterone to LPS stimulated microglia cells changes their inflammatory profile. Therefore, we assessed the levels of nitric oxide (NO), iNOS, IL-6, IL-1ß, TNF-α and COX-2 in untreated, LPS-treated and LPS/Aldosterone-treated microglia cells. Furthermore we analyzed p38-MAP-Kinase and NFκB signaling within these cells. Our results indicate that the co-stimulation with Aldosterone leads to a decrease of the LPS-induced pro-inflammatory effect and thus renders Aldosterone an anti-inflammatory agent in our model system.

Anti-inflammatory properties of Honokiol in activated primary microglia and astrocytes.

Honokiol has been used in traditional medicine for the treatment of inflammatory diseases. Activation of glial cells plays an essential role in neurodegenerative disorders. In this study, we show that Honokiol reduces the inflammatory response to LPS of primary cultures of microglia and astrocytes through the inhibition of pro-inflammatory mediators (iNOS, IL-6, IL-1ß and TNF-α) and the simultaneous stimulation of anti-inflammatory cytokines (IL-10). Expression of KLF4 was induced in microglia and astrocytes after treatment with LPS and this response was mitigated by Honokiol. These findings extend our understanding of the anti-inflammatory properties of Honokiol on central glial cells and support its use as a therapeutic compound in neuroinflammatory disorders.

The antidepressant bupropion is a negative allosteric modulator of serotonin type 3A receptors.

The FDA-approved antidepressant and smoking cessation drug bupropion is known to inhibit dopamine and norepinephrine reuptake transporters, as well as nicotinic acetylcholine receptors (nAChRs) which are cation-conducting members of the Cys-loop superfamily of ion channels, and more broadly pentameric ligand-gated ion channels (pLGICs). In the present study, we examined the ability of bupropion and its primary metabolite hydroxybupropion to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs), and further characterized bupropion's pharmacological effects at these receptors. Mouse 5-HT3ARs were heterologously expressed in HEK-293 cells or Xenopus laevis oocytes for equilibrium binding studies. In addition, the latter expression system was utilized for functional studies by employing two-electrode voltage-clamp recordings. Both bupropion and hydroxybupropion inhibited serotonin-gated currents from 5-HT3ARs reversibly and dose-dependently with inhibitory potencies of 87 µM and 112 µM, respectively. Notably, the measured IC50 value for hydroxybupropion is within its therapeutically-relevant concentrations. The blockade by bupropion was largely non-competitive and non-use-dependent. Unlike its modulation at cation-selective pLGICs, bupropion displayed no significant inhibition of the function of anion-selective pLGICs. In summary, our results demonstrate allosteric blockade by bupropion of the 5-HT3AR. Importantly, given the possibility that bupropion's major active metabolite may achieve clinically relevant concentrations in the brain, our novel findings delineate a not yet identified pharmacological principle underlying its antidepressant effect.

Pupil to limbus ratio: Introducing a simple objective measure using two-box method for measuring early anisocoria and progress of pupillary change in the ICU.

INTRODUCTION: Measurement of static pupillary size in the ICU is of importance in cases of acutely expanding intracranial mass lesions. The inaccuracies with subjective assessment of pupillary size by medical personnel preclude its use in emergent neurological situations. OBJECTIVE: To determine if the ratio of pupil to limbus diameter (PLD ratio) measured by a two-box method is a reliable measure of pupil size for detecting early anisocoria and measuring pupillary changes. MATERIALS AND METHODS: The PLD ratio was defined as the ratio of the pupillary diameter measured at a para-horizontal axial plane with the limbus diameter measured at the same or parallel axial plane. A two-box method was used to estimate the diameters of imaged pupils. Eyes were imaged using an iPhone 4S cellphone camera. Background illumination was measured and kept constant. The pupils of a 78-year-old woman, who presented with a large intra-axial parenchymal hemorrhage, were imaged. The patient had left pupillary miosis in dark but not in bright light. After presenting this case along with the images of the pupillary examination, a group of 21 medical staff were asked several questions on the pupillary examination. Reliability of PLD ratio were assessed via standard error of mean (S.E.M) of PLD ratios for 3 different subjects each imaged under constant illumination and fixation but from different angles to the optical axis. RESULTS: Analysis of questionnaire data together with PLD ratios revealed that ~ 14% and 10% of participants could estimate the pupillary size in darkness and bright light respectively but none were simultaneously accurate indicating that subjective assessment of pupillary size was unreliable. The approach towards a systematic pupillary examination was inconsistent among the participants. The PLD ratio was found to be a reliable measure of pupillary size with standard error of mean below 0.1 mm for the three subjects tested. CONCLUSION: Static pupillary sizes can be objectively and consistently evaluated using PLD ratios using a two-box method. PLD ratios are resistant, within limits, to changes in imaging angle or choice of para-horizontal axes for measurement.

Is initial preservation of deep tendon reflexes in West Nile Virus paralysis a good prognostic sign?

Typical West Nile virus paralysis is characterized by muscle weakness, decreased tone, and loss of deep tendon reflexes attributed to destruction of anterior horn cells. Two cases in which deep tendon reflexes were initially preserved in the presence of profound and persistent muscle weakness are presented here. In both cases, deep tendon reflexes were later severely attenuated or lost, while weakness of the involved muscles remained profound and unchanged. Both patients showed good motor recovery at 6 months. Initial preservation of deep tendon reflexes in the presence of persistent muscle weakness indicates that in the early stages of disease, the muscle weakness in these two cases was not caused by destruction of anterior horn cells. Pathology involving anterior horns preceding AHC destruction could potentially disrupt upper motor neuron pathways to anterior horn cells, causing weakness with initial preserved deep tendon reflexes.

Pathophysiological processes in multiple sclerosis: focus on nuclear factor erythroid-2-related factor 2 and emerging pathways.

Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by the demyelination of neuronal axons. Four different patterns of demyelination have been described, showing the heterogeneity in the immunopathologic processes involved in the demyelination. This review will focus on reactive oxygen species (ROS)-related inflammation in MS. Special emphasis will be placed on the nuclear factor erythroid-2-related factor 2 (Nrf2) as it regulates the transcription of ROS-protective genes. In the cytosol, Nrf2 binds to Keap1 (Kelch-like ECH-associated protein 1), and together they are degraded by the 26S proteasome after ubiquitination. If challenged by ROS Nrf2, binding to Keap1 is abrogated, and it translocates into the nucleus. Here it binds to the antioxidant response element and to a small protein termed Maf (musculoaponeurotic fibrosarcoma oncogene homolog). This leads to an enhanced transcription of ROS protective genes and represents the physiological answer against ROS challenge. It has been shown that dimethyl fumarate (DMF) has the same effect and leads to an enhanced transcription of ROS-protective genes. This response is mediated through a reduced binding of Nrf2 to Keap1, thus resulting in a higher level of free Nrf2 in the cytosol. Consequently, more Nrf2 translocates to the nucleus, promoting transcription of its target genes. DMF has been used for the treatment of psoriasis for many years in Germany without the occurrence of major side effects. In psoriasis, DMF reduces ROS-related inflammation in skin. A DMF analog, BG-12, was recently approved for the treatment of relapsing-remitting MS by the European Union and the US Food and Drug Administration. As an oral formulation, it gives patients a convenient and effective alternative to the injectable immune modulators in the long-term treatment of MS.