Radiological aspects of idiopathic lumbosacral plexitis

Idiopathic Lumbosacral Plexitis is a disease that do not have definitive causes but even starts to be studied by Sander Evans et al. in 1981 hypotheses were put forward related to viral infections, vaccines and heterologous serum. Although more recently studies have showed that the disease can develop without immunological history. Multiple roots and nerves are affected and it can be bilateral. The diferential diagnosis of other pathologies must involves research for tumours, traumas and diabetes. The findings of the disease include: autoimmune demyelination and vasculitis with axonal lesion. The clinicalconditionare characterized by intensive pain, paresis, hypoesthesia in lower members, and a limping gait. The prognosis is positive, however do not have a completely remission without squeals. The treatment has not been defined but is common to uses corticosteroids and immunoglobulin.

Smek1 deficiency exacerbates experimental autoimmune encephalomyelitis by activating proinflammatory microglia and suppressing the IDO1-AhR pathway

Background Experimental autoimmune encephalomyelitis (EAE) is an animal disease model of multiple sclerosis (MS) that involves the immune system and central nervous system (CNS). However, it is unclear how genetic predispositions promote neuroinflammation in MS and EAE. Here, we investigated how partial loss-of-function of suppressor of MEK1 (SMEK1), a regulatory subunit of protein phosphatase 4, facilitates the onset of MS and EAE. Methods C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish the EAE model. Clinical signs were recorded and pathogenesis was investigated after immunization. CNS tissues were analyzed by immunostaining, quantitative polymerase chain reaction (qPCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Single-cell analysis was carried out in the cortices and hippocampus. Splenic and lymph node cells were evaluated with flow cytometry, qPCR, and western blot analysis. Results Here, we showed that partial Smek1 deficiency caused more severe symptoms in the EAE model than in controls by activating myeloid cells and that Smek1 was required for maintaining immunosuppressive function by modulating the indoleamine 2,3-dioxygenase (IDO1)-aryl hydrocarbon receptor (AhR) pathway. Single-cell sequencing and an in vitro study showed that Smek1-deficient microglia and macrophages were preactivated at steady state. After MOG35-55 immunization, microglia and macrophages underwent hyperactivation and produced increased IL-1β in Smek1-/+ mice at the peak stage. Moreover, dysfunction of the IDO1-AhR pathway resulted from the reduction of interferon γ (IFN-γ), enhanced antigen presentation ability, and inhibition of anti-inflammatory processes in Smek1-/+ EAE mice. Conclusions The present study suggests a protective role of Smek1 in autoimmune demyelination pathogenesis via immune suppression and inflammation regulation in both the immune system and the central nervous system. Our findings provide an instructive basis for the roles of Smek1 in EAE and broaden the understanding of the genetic factors involved in the pathogenesis of autoimmune demyelination.

Fulminating Autoimmune Demyelination with Optic Neuropathy in a Case of Pediatric Cerebral Adrenoleukodystrophy: Case Report and Review of the Literature

X-linked adrenoleukodystrophy (ALD) is a leukodystrophy characterized not only by progressive loss of myelin in the central nervous system due to dysmyelination, but also by acute, subacute, or chronic inflammatory demyelination. This results in the phenotypic variability of cerebral ALD (cerALD), which is independent of the genotype. In this manuscript, we report a fulminant presentation with fluctuating encephalopathy and visual loss in a patient with childhood onset cerALD. Brain MRI showed symmetric confluent occipito-temporal demyelination with severe disruption of the blood–brain barrier and prechiasmal optic neuropathy. The patient's cerebral spinal fluid (CSF) demonstrated an elevated IgG index, myelin basic proteins, and oligoclonal bands. Within 48 hours of receiving immunomodulating therapy, the patient's symptoms of psychomotor slowing, visual impairment, and areflexia partially resolved. High plasma C26:0 levels and high ratios of C24/22 and C26/22 were diagnostic of ALD. It has been shown that environmental factors play an important role in the inflammatory demyelination responsible for the severe phenotypes of cerALD.

Aquaporin-4 Expression during Toxic and Autoimmune Demyelination

The water channel protein aquaporin-4 (AQP4) is required for a normal rate of water exchange across the blood–brain interface. Following the discovery that AQP4 is a possible autoantigen in neuromyelitis optica, the function of AQP4 in health and disease has become a research focus. While several studies have addressed the expression and function of AQP4 during inflammatory demyelination, relatively little is known about its expression during non-autoimmune-mediated myelin damage. In this study, we used the toxin-induced demyelination model cuprizone as well as a combination of metabolic and autoimmune myelin injury (i.e., Cup/EAE) to investigate AQP4 pathology. We show that during toxin-induced demyelination, diffuse AQP4 expression increases, while polarized AQP4 expression at the astrocyte endfeet decreases. The diffuse increased expression of AQP4 was verified in chronic-active multiple sclerosis lesions. Around inflammatory brain lesions, AQP4 expression dramatically decreased, especially at sites where peripheral immune cells penetrate the brain parenchyma. Humoral immune responses appear not to be involved in this process since no anti-AQP4 antibodies were detected in the serum of the experimental mice. We provide strong evidence that the diffuse increase in anti-AQP4 staining intensity is due to a metabolic injury to the brain, whereas the focal, perivascular loss of anti-AQP4 immunoreactivity is mediated by peripheral immune cells.

Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination

The endocannabinoid system is associated with protective effects in multiple sclerosis (MS) that involve attenuated innate immune cell responses. Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neuroglial cells as targets and mediators of endocannabinoid signaling in MS is poorly understood. Here we used a microfluidic RT-qPCR screen to assess changes in the expression of the main endocannabinoid signaling genes in astrocytes and microglia purified from female mice during the time-course of experimental autoimmune encephalomyelitis (EAE). We show that astrocytes and microglia upregulate the expression of genes encoding neurotoxic A1 and pro-inflammatory molecules at the acute disease with many of these transcripts remaining elevated during the recovery phase. Both cell populations exhibited an early onset decrease in the gene expression levels of 2-arachidonoylglycerol (2-AG) hydrolytic enzymes that persisted during EAE progression as well as cell-type-specific changes in the transcript levels for genes encoding cannabinoid receptors and molecules involved in anandamide (AEA) signaling. Our results demonstrate that astrocytes and microglia responses to autoimmune demyelination involve alterations in the expression of multiple endocannabinoid signaling-associated genes and suggest that this system may regulate the induction of neurotoxic and pro-inflammatory transcriptional programs in both cell types during MS.

A Clonal NG2-Glia Cell Response in a Mouse Model of Multiple Sclerosis

NG2-glia, also known as oligodendrocyte precursor cells (OPCs), have the potential to generate new mature oligodendrocytes and thus, to contribute to tissue repair in demyelinating diseases like multiple sclerosis (MS). Once activated in response to brain damage, NG2-glial cells proliferate, and they acquire a reactive phenotype and a heterogeneous appearance. Here, we set out to investigate the distribution and phenotypic diversity of NG2-glia relative to their ontogenic origin, and whether there is a clonal NG2-glial response to lesion in an experimental autoimmune encephalomyelitis (EAE) murine model of MS. As such, we performed in utero electroporation of the genomic lineage tracer, StarTrack, to follow the fate of NG2-glia derived from single progenitors and to evaluate their response to brain damage after EAE induction. We then analyzed the dispersion of the NG2-glia derived clonally from single pallial progenitors in the brain of EAE mice. In addition, we examined several morphological parameters to assess the degree of NG2-glia reactivity in clonally-related cells. Our results reveal the heterogeneity of these progenitors and their cell progeny in a scenario of autoimmune demyelination, revealing the ontogenic phenomena at play in these processes.

More on differential diagnosis of demyelinating and hereditary diseases

Демиелинизирующие заболевания являются гетерогенной группой, включающей рассеянный склероз (РС), острый рассеянный энцефаломиелит, оптиконевромиелит (ОНМ), идиопатический поперечный миелит, оптический неврит. Дифференциально-диагностический поиск при демиелинизирующих заболеваниях включает в себя в том числе и наследственные/нейродегенеративные заболевания. Сходство некоторых митохондриальных болезней (МБ) с РС не случайно, поскольку в настоящее время этиопатогенез РС рассматривается не только как аутоиммунная демиелинизация, но и как нейродегенерация, одним из важных патогенетических механизмов которой является митохондриальная дисфункция. В статье проведен краткий анализ пациентов с нарушением зрительных функций и нетипичной для РС клинической картиной. Критерием отбора больных был первичный клинический эпизод, вызванный предположительно воспалительным демиелинизирующим процессом и жалобами на снижение зрительных функций. Demyelinating diseases are heterogeneous group including multiple sclerosis (MS), acute multiple encephalomyelitis, opticoneuromyelitis (ONM), idiopathic transverse myelitis, optical neuritis. The spectrum of differential diagnostic screening in this rare autoimmune disease is variable, including hereditary/neurodegenerative diseases. The similarity of some mitochondrial diseases (MD) with MS is not accidental, since currently etiopathogenesis of MS is considered not only as autoimmune demyelination, but also as neurodegeneration, one of the important pathogenetic mechanisms of which is mitochondrial dysfunction. The article provides a brief analysis of patients with impaired visual functions and atypical clinical-diagnostic picture for MS. The selection criterion for patients was a primary clinical episode caused by a presumably inflammatory demyelinating process and complaints of decreased visual functions.