Atypical antipsychotics in multiple sclerosis: A review of their in vivo immunomodulatory effects.

INTRODUCTION: The high efficacy of atypical antipsychotics (AAP) in treating diverse psychiatric disorders has been partly attributed to their capacity to curb neuroinflammation, a shared aspect of these diseases. These immunomodulatory properties of AAP have lately been explored in the context of multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS. METHODS: This study aimed to review in vivo studies reporting on the therapeutic effects of AAP both in EAE, the main animal model of MS and in cuprizone-induced demyelination. For that matter we conducted a literature search and a screening process that eventually yielded 8 eligible studies. RESULTS: All studies agreed on the efficiency of AAP to dramatically reduce EAE severity and delay its onset, while suppressing the production of numerous inflammatory cytokines. Clozapine showcased similar yet more intense effects than risperidone, quetiapine and olanzapine, significantly attenuating CD4 T cell infiltration and myeloid cell activation, while upregulating Tregs. Clozapine also downregulated chemokines responsible for the migration of immune cells in the CNS and caused dopamine receptor levels in the brain of EAE mice to rise. DISCUSSION: Taken together, these findings unanimously attest to the anti-inflammatory and immunomodulatory properties of AAP, suggesting that their therapeutic potential expands beyond their current neuropsychiatric applications. Despite the salutary effects of AAP in MS reported in vivo, a clinical trial of clozapine on MS patients failed to confirm preclinical findings due to low acceptability of AAP and early participant withdrawal. CONCLUSION: Although preclinical evidence unquestionably supports the multifaceted beneficial properties of AAP in MS, further investigation is required to elucidate the pharmacodynamic profile of these agents and allow for their proper clinical testing on MS patients.

Atypical bilateral acute retinal necrosis in a coronavirus disease 2019 positive immunosuppressed patient.

PURPOSE: To present the clinical features of a rare case of atypical acute retinal necrosis in a Coronavirus Disease 2019 (COVID-19) positive immunosuppressed patient. METHODS: Retrospective observational case report. RESULTS: A 75-year-old lady presented with a left eye pan uveitis picture with vitritis and extensive peripheral and mid-peripheral necrotising retinitis. In the right eye, she had a very mild superior peripheral retinitis with minimal anterior or vitreous inflammation. Two months prior to her diagnosis she completed a course of rituximab and chlorambucil chemotherapy for a relapse of diffuse large cell B-cell lymphoma (DLBCL). The patient's nasopharyngeal swabs tested positive for COVID-19 in a reverse transcription polymerase chain reaction (RT-PCR) assay. The vitreous sample PCR tested positive for Varicella Zoster Virus and was negative for SARS-CoV-2. CONCLUSION AND SIGNIFICANCE: To the best of our knowledge this is the first description of a case that has undergone vitreous PCR testing for COVID-19. It is interesting to note the high level of vitreous inflammation which would not be expected in an immunosuppressed state. We present a number of possible links between the SARS-CoV-2 virus and the unusual ocular presentation of bilateral VZV viral retinitis in this patient.While extra ocular VZV outbreaks have been reported with rituximab treated patients, this report should also raise the awareness of VZV related viral retinitis in DLBCL patients on rituximab chemotherapy which is a very rare occurrence.This case may provide some evidence to healthcare policy makers who are making decisions regarding the re-introduction of routine Ophthalmic surgery.

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models.

Background: Increased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy. Objective: This review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients. Methods: Through a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria. Results: In vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS. Conclusion: Antidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.

Computed tomography and radiographic indirect lymphography for visualization of mammary lymphatic vessels and the sentinel lymph node in normal cats.

The potential of computed tomography indirect lymphography (CT-indirect lymphography) and radiographic indirect lymphography to demonstrate the draining lymphatic vessels and sentinel lymph node of normal mammary glands was tested in 31 healthy female cats. The lymphatic drainage of each mammary gland was studied initially by CT-indirect lymphography after intramammary injection of 0.5 ml of iopamidol, followed by images acquired at 1, 5, 15, and 30 min after injection. One day after CT-indirect lymphography, the lymph drainage of the mammary gland was assessed using radiographic in direct lymphography af terintramammary injection of 0.5 ml of ethiodized oil followed by radiographs made at 1, 5, 15, 30, 45, and 60 min after injection. The time between intramammary injection and opacification of the draining mammary lymphatic vessels and the sentinel lymph node, the duration of adequate opacification of the draining mammary lymphatic vessels and of the sentinel lymph node and also the number and course of draining mammary lymphatic vessels and location of sentinel lymph node were compared for CT-indirect lymphography vs. radiographic indirect lymphography in each examined gland. This results suggest that radiographic indirect lymphography is easy to perform and can be used for accurate demonstration of the draining lymphatic pathways of mammary glands in radiographs made at 5-30 min after injection. However, CT-indirect lymphography was able to better demonstrate small lymphatic vessels and accurately define the exact topography of the sentinel lymph node in images acquired at 1 min after injection.