Tapering Doses Of Dexamethasone Research Articles

Case Report: Central Nervous System Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Non-HIV Patient

Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is an abnormal, excessive immune response against live or dead Mycobacteria tuberculosis that may occur during or even after completion of anti-TB therapy, commonly in HIV-infected patients. However, this has also been reported amongst HIV negative patients. We report a case of CNS TB-IRIS in a 57-year-old HIV negative man with miliary TB and tuberculoma. He first presented with 4 months of chronic constitutional symptoms. His symptoms improved on standard anti-TB (isoniazid, rifampicin, ethambutol, pyrazinamide) initially, but he developed worsening left hemiparesis after 1 month of treatment. He was restarted on tapering dose of dexamethasone, and anti-TB was intensified with intramuscular streptomycin for 2 months. His gained full muscle power 4 months later. Serial brain imaging subsequently showed slow treatment response with partial resolution of brain lesions. However, he developed another episode of left hemiparesis with facial asymmetry and slurred speech after 16 months of anti-TB treatment. Repeated MRI brain showed 2 large frontal ring enhancing lesions and lesions in cerebellar hemispheres and vermis regions. Due to diagnostic uncertainties and compressive nature of the brain lesions, craniotomy and excision biopsy of the right frontal lesion were performed. There were no evidence of drug resistant TB and no other brain pathologies were found. Moxifloxacin was added post operatively to achieve better CNS penetration. Patient eventually recovered and achieved full muscle strength of left upper and lower limbs.

Antenatal betamethasone enhanced the detrimental effects of postnatal dexamethasone on hyperoxic lung and brain injuries in newborn rats.

PurposeTo determine the effects of antenatal betamethasone and/or postnatal dexamethasone administration on hyperoxic lung and brain injuries in newborn rats.MethodsNewborn Sprague-Dawley rats were divided into five experimental groups: normoxia-vehicle-vehicle group, hyperoxia-vehicle-vehicle group, hyperoxia-betamethasone-vehicle group, hyperoxia-vehicle-dexamethasone group, and hyperoxia-betamethasone-dexamethasone group according to (i) whether rats were exposed to normoxia or hyperoxia after birth to postnatal day (P) 14, (ii) whether antenatal betamethasone (0.2mg/kg) or vehicle was administered to pregnant rats at gestation days 19 and 20, and (iii) whether three tapering doses of dexamethasone (0.5, 0.3, 0.1mg/kg per day) or vehicle were administered on P5, 6 and 7, respectively. The lungs and brains were harvested for histological and biochemical analyses at P8 and P14.ResultsPostnatal dexamethasone but not antenatal betamethasone significantly enhanced hyperoxia-induced reduction in body weight gain and alveolarization and increased lung terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells both at P8 and P14, transiently increased hyperoxia-induced reductions in brain weight gain and angiogenesis, and increase in brain TUNEL-positive cells at P8 but not at P14. Co-administration of antenatal betamethasone significantly enhanced dexamethasone-induced impairments in alveolarization both at P8 and P14, transient increases in lung and brain oxidative stresses, and increases in brain TUNEL-positive cells at P8 but not at P14.ConclusionAlthough postnatal dexamethasone but not antenatal betamethasone alone significantly increased hyperoxic lung and brain injuries, co-administration of antenatal betamethasone significantly enhanced the detrimental effects of postnatal dexamethasone on hyperoxic lung and brain injuries in newborn rats.

Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor α Expression in Adolescent Female Rats

Previous studies showed that neonatal dexamethasone treatment (NDT) transiently impaired hippocampal function in male rats. Hippocampal estrogen receptors (ERs) participate in avoidance learning. As previous studies focused on males only, this study was aimed to investigate the NDT effects on the hippocampal function of female rats. Newborn Wistar female rats were subjected to a tapering dose of dexamethasone (0.5mg, 0.3mg, and 0.1mg/kg, subcutaneously) from postnatal days 1 to 3 and were subjected to experiments at the age of 6weeks (adolescence). Brain slice extracellular recording and the inhibitory avoidance (IA) test were used to evaluate the NDT effects on hippocampal function. The results showed that NDT completely blocked the hippocampal long-term potentiation (LTP) formation and IA learning of adolescents. The expression of hippocampal estrogen receptor alpha (ERα) was attenuated in NDT subjects. Reduced histone acetylation of the ERα gene was found, possibly explaining the reduced hippocampal ERα expression in NDT female rats. Suprafusion of estradiol (E2) partially restored the hippocampal LTP formation in adolescent NDT female rats. Coadministration of the histone deacetylase inhibitor trichostatin-A restored the hippocampal ERα expression, hippocampal LTP formation, and IA learning in adolescent NDT female rats. Collectively, these results suggested that NDT has an epigenetic modulation effect on the expression of hippocampal ERα, which is responsible for its adverse effect on hippocampal function.

Administration of corticosteroids in mandibular fractures- A double edged sword

Aim: To compare the effectiveness of five day versus one day perioperative dose of corticosteroids in mandibular fractures operated via an intraoral approach. Materials and method: This is a prospective, randomized, controlled, double blind clinical study involving 144 subjects from (2011-2015) who underwent Open reduction and internal fixation (ORIF) via intraoral approach for simple, non-comminuted, fractures of mandible. The subjects were randomly assigned into 2 groups of 72 each by lottery method. Patients in Group A (control group) were administered a tapering dose of Dexamethasone 8mg IV over 5days while patients in Group B (test group) received one preoperative and one postoperative dose of intravenous (IV) Dexamethasone. Both groups were administered 1 st dose of 8mg Dexamethasone simultaneously. Both the groups were followed up on the 1 st day, 3 rd day, 1 st week post operatively and were evaluated for pain (VAS on 10cm scale), swelling, paraesthesia, nausea and vomiting and any other adverse effects. Results: Postoperatively swelling at 48hours was higher in test group by 7.5% which was statistically significant (p = 0.001). Paraesthesia was also 10% higher in test group but wound dehiscence was higher in control group by 7.5%. The test group also recorded lower incidence of infection clinically as well as radiographically. Conclusion: 5 day steroid regimen and 1 day regimen were equally effective in increasing patients comfort by reducing swelling. However, 1 day regimen was significantly satisfactory with regard to healing and long term outcomes while being cost effective at the same time.

Fatal gastrointestinal hemorrhage in a young boy with newly diagnosed metastatic medulloblastoma on high dose dexamethasone.

A 10-year-old boy with newly diagnosed metastatic medulloblastoma was placed on high dose dexamethasone and ranitidine prior to surgery. The child underwent subtotal resection and was discharged 5 days postoperatively with an uneventful hospital course on a tapering dose of dexamethasone and ranitidine. Over the next 2 days the patient complained of mild abdominal distension with flatulence, without pain, vomiting, or dysmotility. On follow-up in clinic 5 days after discharge, he had normal vital signs when he suddenly became pale and had loss of consciousness. Emergent computerized tomography of the head showed no acute hemorrhage and complete blood count revealed hemoglobin of 4.2 gm/dL. In spite of maximum resuscitation with copious blood products the patient died. Autopsy revealed evidence of duodenal perforation with intraluminal hemorrhage. This case demonstrates a rare fatal complication of high dose dexamethasone therapy even with concurrent gastrointestinal prophylactic therapy. We provide a review of the limited literature on steroid use in pediatric neurooncology with regard to gastrointestinal bleeding.

Acute effects of neonatal dexamethasone treatment on proliferation and astrocyte immunoreactivity in hippocampus and corpus callosum: Towards a rescue strategy

Dexamethasone (DEX), a synthetic glucocorticoid, has been used to treat respiratory distress syndrome in prematurely born infants. Despite the important short-term benefit on lung function, there is growing concern about the long-term outcome of this treatment, since follow-up studies of prematurely born infants have shown lasting adverse neurodevelopmental effects. Since the mechanism underlying these neurodevelopmental impairments is largely unknown, the aim of the present study was (i) to investigate the acute effects of neonatal DEX treatment on the developing brain; and (ii) to block specifically the effects of DEX on the brain by central administration of the glucocorticoid receptor (GR) antagonist mifepristone. Long Evans rat pups were injected subcutaneously with tapering doses of DEX or saline (SAL) on postnatal days (pnd) 1, 2 and 3. Separate groups received intracerebroventricular injections with mifepristone prior to DEX treatment. On pnd 4 and 10, pups were sacrificed and brains collected for analysis of cell proliferation (Ki-67) and astrogliosis (GFAP). We report that neonatal DEX treatment reduced hippocampal cell proliferation on pnd 4, an effect that was normalized by pnd 10. Although on pnd 4, GFAP expression was not affected, DEX treatment caused a significant reduction in the number and density of astrocytes in hippocampus and corpus callosum on pnd 10, which was normalized by mifepristone pre-treatment. These acute alterations in the neonate brain might underlie later functional impairments reported in DEX-treated animals and humans and further illustrate the impact of early GR activation on brain development.

Effects of Neonatal Corticosteroid Treatment on Hippocampal Synaptic Function

There is growing concern about long-term neurodevelopmental outcomes after neonatal corticosteroid treatment for chronic lung disease (CLD). Here, we use a protocol with tapering doses of dexamethasone (DEX) or hydrocortisone (HC) proportional to those used in preterm infants to examine the long-term consequences of these treatments on hippocampal synaptic plasticity and associative memory in later life. We found that neonatal DEX, but not HC, treatment impairs long-term potentiation (LTP) but enhances long-term depression (LTD) induction in adolescent rats. The effects of neonatal DEX treatment on LTP and LTD were prevented when the animals were given glucocorticoid receptor antagonist, RU38486, before DEX administration. We also found that neonatal DEX, but not HC, treatment induces a profound increase in the autophosphorylation of a isoform of Ca2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. In addition, only neonatal DEX treatment disrupts memory retention in rats subjected to passive avoidance learning tasks. These results demonstrate that only neonatal DEX treatment alters the hippocampal synaptic plasticity and associative memory formation in later life and thus suggest that HC may be a safer alternative to DEX for the treatment of CLD in the neonatal period.

Reversible neurotoxicity following hyperfractionated radiation therapy of brain stem glioma

Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. 18FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation-related neurotoxicity.