Challenges in the acute management of profound hyponatremia presenting with severe symptoms

Currently available guidelines in the acute management of severely symptomatic hypotonic hyponatremia vary in their approach to the use of hypertonic saline. In the acute setting, deciding on when to implement available treatment algorithm using hypertonic saline may be difficult, given that the duration of hyponatremia and potential alternative diagnoses presenting with similar symptoms may be hard to establish promptly. We present the case of a young female with symptomatic profound hyponatremia who subsequently developed osmotic demyelination syndrome due to rapid overcorrection of serum sodium concentration. We discuss the interplay between the dynamic pathophysiological processes responsible for hypotonic hyponatremia in adrenal insufficiency and conduct a detailed analysis of currently available guidelines to highlight the challenges in acute and reactive treatment in clinical practice.     

大鼠急性经口1,1-二氨基-2,2-二硝基乙烯的毒代动力学研究

建立大鼠血液中1,1-二氨基-2,2-二硝基乙烯(FOX-7)的检测方法，将30只健康SPF级SD大鼠随机分为空白对照组、200和500mg/kgFOX-7染毒组，每组10只。采用一次性经口灌胃方式染毒，染毒容量为ImL/lOOg。于染毒后第0.5、1、2、4、8、12、24h对大鼠进行眼眶后静脉丛采血，使用紫外可见分光光度计检测血中FOX-7浓度。使用PhoenixWinNonlin6.1软件进行血药浓度-时间数据分析与毒代参数计算。大鼠单次灌胃FOX-7200和500mg/kg后，药-时曲线下面积AUC(0-24)分别为(27.01±L94)^g/(h?L)和(29.26±3.31)^^(h-L),AUC(0-?>分别为(42.。1±2.18)阿/(h-L)和(4L51±3.66)Mg/(h?L)；达峰浓度Cmax分别为(1.82±0,12)Mg/ml和(2.33±0,20)阿/ml,达峰时间y.为2h；半衰期知2分别为(10.83±2,77)h和(8.66±3,01)h。本研究为FOX-7毒代动力学模型的完善提供了科学依据。     

Demyelinating processes in aging and stroke in the central nervous system and the prospect of treatment strategy

Demyelination occurs in response to brain injury and is observed in many neurodegenerative diseases. Myelin is synthesized from oligodendrocytes in the central nervous system, and oligodendrocyte death‐induced demyelination is one of the mechanisms involved in white matter damage after stroke and neurodegeneration. Oligodendrocyte precursor cells (OPCs) exist in the brain of normal adults, and their differentiation into mature oligodendrocytes play a central role in remyelination. Although the differentiation and maturity of OPCs drive endogenous efforts for remyelination, the failure of axons to remyelinate is still the biggest obstacle to brain repair after injury or diseases. In recent years, studies have made attempts to promote remyelination after brain injury and disease, but its cellular or molecular mechanism is not yet fully understood. In this review, we discuss recent studies examining the demyelination process and potential therapeutic strategies for remyelination in aging and stroke. Based on our current understanding of the cellular and molecular mechanisms underlying remyelination, we hypothesize that myelin and oligodendrocytes are viable therapeutic targets to mitigate brain injury and to treat demyelinating‐related neurodegeneration diseases.     

Optimal duration of percutaneous microballoon compression for treatment of trigeminal nerve injury简

Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, compression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 ± 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demyelination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experimental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percutaneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.     

NG2 cells (polydendrocytes): Listeners to the neural network with diverse properties

NG2 cells (polydendrocytes) are the fourth major non‐neuronal cell type in the central nervous system parenchyma. They exhibit diverse properties, ranging from their well‐established role as oligodendrocyte precursors to their ability to respond to neurotransmitters released by synaptic and non‐synaptic mechanisms. The functional diversity of NG2 cells has prompted the question of whether they represent a single cellular entity or multiple distinct cell populations. This review first summarizes recent findings on the nature and mechanism underlying the diversity of NG2 cells with regard to their proliferative and differentiation behavior. This will be followed by a synopsis of observations on how their microenvironment, particularly neuronal activity, influences their dynamic behavior, and how these changes in NG2 cells could in turn influence neural function and animal behavior. GLIA 2014;62:1195–1210     

Axonal dysfunction,dysmyelination, and conduction failure in hereditary neuropathy with liability to pressure palsies

Introduction: Patients with hereditary neuropathy with liability to pressure palsies (HNPP) manifest with episodes of focal paresis when exposed to mechanical stress, although the basis for vulnerability to conduction block remains relatively unexplained. Methods: Axonal excitability techniques were utilized to provide insights into pathophysiological mechanisms in 13 HNPP patients, stimulating median motor and sensory axons at the wrist. Results: In HNPP, distal latencies were prolonged, and motor and sensory amplitudes were reduced. Threshold was increased. Depolarizing and hyperpolarizing electrotonus was greater, and resting current–threshold slope was reduced. There were greater threshold changes in superexcitability, and refractoriness was decreased. Conclusions: Taken together, excitability testing in patients with HNPP established axonal hyperpolarization in both motor and sensory axons that may be attributable to changes in nerve architecture. In turn, the hyperpolarized resting membrane potential in HNPP may be a major predisposing factor for development of conduction block with mechanical stresses. Muscle Nerve 49 : 858–865, 2014     

Inflammatory infratentorial progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis

An 84–year‐old man with rheumatoid arthritis (RA) treated with methotrexate, developed progressive confusion and cerebellar symptoms, and died approximately 2 months later. Neuropathological examination revealed progressive multifocal leukoencephalopathy (PML) involving the cerebellum and brainstem. The affected tissues displayed intense infiltrations by CD8+ T‐cells and microglia. JC virus was localized in oligodendroglia and cerebellar granule cells. This case illustrates unusual localization of inflammatory PML in a patient with RA treated with methotrexate.     

Deficient arginase II expression without alteration in arginase I expression attenuated experimental autoimmune encephalomyelitis in mice

In the past there have been a multitude of studies that ardently support the role of arginase II (Arg II) in vascular and endothelial disorders; however, the regulation and function of Arg II in autoimmune diseases has thus far remained unclear. Here we report that a global Arg II null mutation in mice suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. During EAE, both Arg I and Arg II were induced in spinal cords, but only Arg II was induced in spleens and splenic dendritic cells (DCs). DC activation by lipopolysaccharide (LPS), CD40L or TLR8 agonist significantly enhanced Arg II expression without affecting Arg I expression. Conversely, DC differentiating cytokines [IL‐4 and granulocyte macrophage‐colony‐stimulating factor (GM‐CSF)] yielded opposite effects. In addition, Arg I and Arg II were regulated differentially during Th1 and Th17 cell polarization. Arg II deficiency in mice delayed EAE onset, ameliorated clinical symptoms and reduced myelin loss, accompanied by a remarkable reduction in the EAE‐induced spinal cord expression of Th17 cell markers (IL‐17 and RORγt). The abundance of Th17 cells and IL‐23⁺ cells in relevant draining lymph nodes was significantly reduced in Arg II knockout mice. In activated DCs, Arg II deficiency significantly suppressed the expression of Th17‐differentiating cytokines IL‐23 and IL‐6. Interestingly, Arg II deficiency did not lead to any compensatory increase in Arg I expression in vivo and in vitro. In conclusion, Arg II was identified as a factor promoting EAE likely via an Arg I‐independent mechanism. Arg II may promote EAE by enhancing DC production of Th17‐differentiating cytokines. Specific inhibition of Arg II could be a potential therapy for multiple sclerosis.     

Diagnostic red flags: steroid‐treated malignant CNS lymphoma mimicking autoimmune inflammatory demyelination

The presence of inflammation and demyelination in a central nervous system (CNS) biopsy points towards a limited, yet heterogeneous group of pathologies, of which multiple sclerosis (MS) represents one of the principal considerations. Inflammatory demyelination has also been reported in patients with clinically suspected primary central nervous system lymphoma (PCNSL), especially when steroids had been administered prior to biopsy acquisition. The histopathological changes induced by corticosteroid treatment can range from mild reduction to complete disappearance of lymphoma cells. It has been proposed that in the absence of neoplastic B cells, these biopsies are indistinguishable from MS, yet despite the clinical relevance, no histological studies have specifically compared the two entities. In this work, we analyzed CNS biopsies from eight patients with inflammatory demyelination in whom PCNSL was later histologically confirmed, and compared them with nine well defined early active multiple sclerosis lesions. In the patients with steroid‐treated PCNSL (ST‐PCNSL) the interval between first and second biopsy ranged from 3 to 32 weeks; all of the patients had received corticosteroids before the first, but not the second biopsy. ST‐PCNSL patients were older than MS patients (mean age: ST‐PCNSL: 62 ± 4 years, MS: 30 ± 2 years), and histological analysis revealed numerous apoptoses, patchy and incomplete rather than confluent and complete demyelination and a fuzzy lesion edge. The loss of Luxol fast blue histochemistry was more profound than that of myelin proteins in immunohistochemistry, and T cell infiltration in ST‐PCNSL exceeded that in MS by around fivefold (P = 0.005). Our data indicate that in the presence of extensive inflammation and incomplete, inhomogeneous demyelination, the neuropathologist should refrain from primarily considering autoimmune inflammatory demyelination and, even in the absence of lymphoma cells, instigate close clinical follow‐up of the patient to detect recurrent lymphoma.