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JAAPA : Official Journal of the... Oct 2019Despite the high incidence of hyponatremia, the correct approach to management, particularly in patients with severe hyponatremia (serum sodium of 120 mEq/L or less), is... (Review)
Review
Despite the high incidence of hyponatremia, the correct approach to management, particularly in patients with severe hyponatremia (serum sodium of 120 mEq/L or less), is controversial. This article reviews two major consensus guidelines and recent studies that can help clinicians make evidence-based treatment decisions and reduce patient risk for iatrogenic osmotic demyelination from overly aggressive treatment.
Topics: Demyelinating Diseases; Disease Management; Humans; Hyponatremia; Iatrogenic Disease; Practice Guidelines as Topic; Risk Assessment; Saline Solution, Hypertonic
PubMed: 31567743
DOI: 10.1097/01.JAA.0000578796.15417.09 -
Continuum (Minneapolis, Minn.) Oct 2017This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help... (Review)
Review
PURPOSE OF REVIEW
This article reviews the chronic demyelinating neuropathies, with a focus on the diagnosis and treatment of immune-mediated neuropathies and the features that can help differentiate immune-mediated neuropathies from other chronic demyelinating peripheral nerve conditions.
RECENT FINDINGS
Advances in clinical phenotyping and outcomes assessment have enabled neurologists to improve disease recognition, treatment, and disease monitoring. Our understanding of the immunopathogenesis of demyelinating neuropathies is evolving. Identification of new antibodies and recognition that node of Ranvier dysfunction may be an early pathogenic feature may herald further diagnostic and treatment advancements.
SUMMARY
The chronic demyelinating polyneuropathies are heterogeneous. The clinical and diagnostic features are sometimes overlapping, and the specific disorders are variable in pathogenesis, treatment, and prognosis. This heterogeneity underscores the importance of achieving diagnostic accuracy and implementing disease-specific treatment approaches.
Topics: Chronic Disease; Demyelinating Diseases; Humans; Polyneuropathies
PubMed: 28968364
DOI: 10.1212/CON.0000000000000517 -
Neuroscience Mar 2017Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with...
Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with early onset or progressive forms of the disease and prognosticate rapid progression to disability and death. Gray matter atrophy, hippocampal lesions, interneuron loss, and elevated juxtacortical lesion burden have been identified in MS patients with seizures; however, translational studies aimed at elucidating the pathophysiological processes underlying MS epileptogenesis are limited. Here, we report that cuprizone-mediated chronically demyelinated (9-12weeks) mice exhibit marked changes to dorsal hippocampal electroencephalography (EEG) and evidence of overt seizure activity. Immunohistochemical (IHC) analyses within the hippocampal CA1 region revealed extensive demyelination, loss of parvalbumin (PV) interneurons, widespread gliosis, and changes in aquaporin-4 (AQP4) expression. Our results suggest that chronically demyelinated mice are a valuable model with which we may begin to understand the mechanisms underlying demyelination-induced seizures.
Topics: Animals; Aquaporin 4; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Electroencephalography; Gliosis; Hippocampus; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Multiple Sclerosis; Neurons; Seizures
PubMed: 28153692
DOI: 10.1016/j.neuroscience.2017.01.035 -
Journal of Neuroendocrinology Jul 2022Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there... (Review)
Review
Demyelination results from the pathological loss of myelin and is a hallmark of many neurodegenerative diseases. Despite the prevalence of demyelinating diseases, there are no disease modifying therapies that prevent the loss of myelin or promote remyelination. This review aims to summarize studies in the field that highlight the importance of nuclear hormone receptors in the promotion and maintenance of myelination and the relevance of nuclear hormone receptors as potential therapeutic targets for demyelinating diseases. These nuclear hormone receptors include the estrogen receptor, progesterone receptor, androgen receptor, vitamin D receptor, thyroid hormone receptor, peroxisome proliferator-activated receptor, liver X receptor, and retinoid X receptor. Pre-clinical studies in well-established animal models of demyelination have shown a prominent role of these nuclear hormone receptors in myelination through their promotion of oligodendrocyte maturation and development. The activation of the nuclear hormone receptors by their ligands also promotes the synthesis of myelin proteins and lipids in mouse models of demyelination. There are limited clinical studies that focus on how the activation of these nuclear hormone receptors could alleviate demyelination in patients with diseases such as multiple sclerosis (MS). However, the completed clinical trials have reported improved clinical outcome in MS patients treated with the ligands of some of these nuclear hormone receptors. Together, the positive results from both clinical and pre-clinical studies point to nuclear hormone receptors as promising therapeutic targets to counter demyelination.
Topics: Animals; Demyelinating Diseases; Humans; Mice; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; Receptors, Cytoplasmic and Nuclear; Remyelination
PubMed: 35734821
DOI: 10.1111/jne.13171 -
Progress in Neurobiology Mar 2024Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple... (Review)
Review
Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple sclerosis (MS) are at a greater risk of developing epilepsy compared to non-MS individuals. These bidirectional connections raise the question of whether both pathological conditions share common pathogenic mechanisms. This review focuses on the reciprocal relationship between epilepsy and demyelination diseases. We commence with an overview of the neurological basis of epilepsy and demyelination diseases, followed by an exploration of how our comprehension of these two disorders has evolved in tandem. Additionally, we discuss the potential pathogenic mechanisms contributing to the interactive relationship between these two diseases. A more nuanced understanding of the interplay between epilepsy and demyelination diseases has the potential to unveiling the molecular intricacies of their pathological relationships, paving the way for innovative directions in future clinical management and treatment strategies for these diseases.
Topics: Humans; Demyelinating Diseases; Multiple Sclerosis; Epilepsy
PubMed: 38378072
DOI: 10.1016/j.pneurobio.2024.102588 -
The Medical Clinics of North America Jan 2024Acquired demyelinating syndromes (ADS) are a heterogenous group of inflammatory demyelinating conditions that include presentations of optic neuritis, transverse... (Review)
Review
Acquired demyelinating syndromes (ADS) are a heterogenous group of inflammatory demyelinating conditions that include presentations of optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis. They can be monophasic or can develop into relapsing episodes of the initial demyelinating event or evolve to include other types of demyelination. Significant progress has been made in differentiating subtypes of ADS that differ in their tendency to relapse and in which anti-inflammatory therapies are effective. Differentiating between these subtypes is important for the optimal management of these patients. Clinical features, labs (especially autoantibodies), and MRI findings can help to differentiate between the different ADS.
Topics: Humans; Magnetic Resonance Imaging; Demyelinating Diseases; Diagnosis, Differential
PubMed: 37951658
DOI: 10.1016/j.mcna.2023.05.017 -
Acta Neuropathologica Communications Mar 2021Cognitive dysfunction occurs in greater than 50% of individuals with multiple sclerosis (MS). Hippocampal demyelination is a prominent feature of postmortem MS brains...
Cognitive dysfunction occurs in greater than 50% of individuals with multiple sclerosis (MS). Hippocampal demyelination is a prominent feature of postmortem MS brains and hippocampal atrophy correlates with cognitive decline in MS patients. Cellular and molecular mechanisms responsible for neuronal dysfunction in demyelinated hippocampi are not fully understood. Here we investigate a mouse model of hippocampal demyelination where twelve weeks of treatment with the oligodendrocyte toxin, cuprizone, demyelinates over 90% of the hippocampus and causes decreased memory/learning. Long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons is considered to be a major cellular readout of learning and memory in the mammalian brain. In acute slices, we establish that hippocampal demyelination abolishes LTP and excitatory post-synaptic potentials of CA1 neurons, while pre-synaptic function of Schaeffer collateral fibers is preserved. Demyelination also reduced Ca-mediated firing of hippocampal neurons in vivo. Using three-dimensional electron microscopy, we investigated the number, shape (mushroom, stubby, thin), and post-synaptic densities (PSDs) of dendritic spines that facilitate LTP. Hippocampal demyelination did not alter the number of dendritic spines. Surprisingly, dendritic spines appeared to be more mature in demyelinated hippocampi, with a significant increase in mushroom-shaped spines, more perforated PSDs, and more astrocyte participation in the tripartite synapse. RNA sequencing experiments identified 400 altered transcripts in demyelinated hippocampi. Gene transcripts that regulate myelination, synaptic signaling, astrocyte function, and innate immunity were altered in demyelinated hippocampi. Hippocampal remyelination rescued synaptic transmission, LTP, and the majority of gene transcript changes. We establish that CA1 neurons projecting demyelinated axons silence their dendritic spines and hibernate in a state that may protect the demyelinated axon and facilitates functional recovery following remyelination.
Topics: Animals; Astrocytes; Cognitive Dysfunction; Cuprizone; Demyelinating Diseases; Dendritic Spines; Disease Models, Animal; Hippocampus; Long-Term Potentiation; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron; Multiple Sclerosis; Neurons; Post-Synaptic Density; Sequence Analysis, RNA
PubMed: 33648591
DOI: 10.1186/s40478-021-01130-9 -
Neuromolecular Medicine Sep 2017One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin... (Review)
Review
One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system. A huge variety of models have been developed to help improve our understanding of these processes. Nevertheless, no single model allows us to study all the processes involved in remyelination and usually more than one is needed to provide a full picture of related mechanisms. In this review, we summarise the most commonly used models for studying myelination, demyelination and remyelination and we analyse them critically to outline the most suitable ways of using them.
Topics: Animals; Animals, Genetically Modified; Axons; Cells, Cultured; Coculture Techniques; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Models, Animal; Myelin Sheath; Oligodendrocyte Precursor Cells; Oligodendroglia; Schwann Cells; Species Specificity; Toxicity Tests; Virus Diseases; Zebrafish
PubMed: 28536996
DOI: 10.1007/s12017-017-8442-1 -
Glia Oct 2020The presence of peripheral myelinating cells in the central nervous system (CNS) has gained the neurobiologist attention over the years. Despite the confirmed presence... (Review)
Review
The presence of peripheral myelinating cells in the central nervous system (CNS) has gained the neurobiologist attention over the years. Despite the confirmed presence of Schwann cells in the CNS in pathological conditions, and the long list of their beneficial effects on central remyelination, the cues that impede or allow Schwann cells to successfully conquer and remyelinate central axons remain partially undiscovered. A better knowledge of these factors stands out as crucial to foresee a rational therapeutic approach for the use of Schwann cells in CNS repair. Here, we review the diverse origins of Schwann cells into the CNS, both peripheral and central, as well as the CNS components that inhibit Schwann survival and migration into the central parenchyma. Namely, we analyze the astrocyte- and the myelin-derived components that restrict Schwann cells into the CNS. Finally, we highlight the unveiled mode of invasion of these peripheral cells through the central environment, using blood vessels as scaffolds to pave their ways toward demyelinated lesions. In short, this review presents the so far uncovered knowledge of this complex CNS-peripheral nervous system (PNS) relationship.
Topics: Animals; Cell Movement; Cell Survival; Central Nervous System; Demyelinating Diseases; Humans; Myelin Sheath; Peripheral Nervous System; Remyelination; Schwann Cells
PubMed: 32027054
DOI: 10.1002/glia.23788 -
Acta Neuropathologica Communications Nov 2018Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. Active... (Review)
Review
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. Active MS lesions mainly consist of macrophages and microglia containing abundant intracellular myelin remnants. Initial studies showed that these foamy phagocytes primarily promote MS disease progression by internalizing myelin debris, presenting brain-derived autoantigens, and adopting an inflammatory phenotype. However, more recent studies indicate that phagocytes can also adopt a beneficial phenotype upon myelin internalization. In this review, we summarize and discuss the current knowledge on the spatiotemporal physiology of foamy phagocytes in MS lesions, and elaborate on extrinsic and intrinsic factors regulating their behavior. In addition, we discuss and link the physiology of myelin-containing phagocytes to that of foamy macrophages in other disorders such atherosclerosis.
Topics: Animals; Demyelinating Diseases; Humans; Macrophages; Microglia; Multiple Sclerosis; Myelin Sheath; Phagocytes
PubMed: 30454040
DOI: 10.1186/s40478-018-0628-8