ABSTRACT
OBJECTIVE: This article discusses the clinical manifestations and management of infectious peripheral neuropathies. LATEST DEVELOPMENTS: Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease. ESSENTIAL POINTS: Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.
Subject(s)
COVID-19 , Communicable Diseases , Peripheral Nervous System Diseases , Humans , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/therapy , COVID-19 Vaccines , Pandemics , SARS-CoV-2 , Communicable Diseases/complicationsSubject(s)
Ataxia/etiology , Carotid Artery Thrombosis/diagnostic imaging , Carotid Artery, Internal, Dissection/diagnostic imaging , Headache/etiology , Infarction, Middle Cerebral Artery/diagnostic imaging , Vertebral Artery Dissection/diagnostic imaging , Adult , Anticoagulants/therapeutic use , Aphasia/etiology , Carotid Artery Thrombosis/complications , Carotid Artery Thrombosis/drug therapy , Carotid Artery, Internal , Carotid Artery, Internal, Dissection/complications , Carotid Artery, Internal, Dissection/drug therapy , Chronic Disease , Female , Hand , Heparin/therapeutic use , Humans , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/etiology , Neurologic Examination , Radiography , Vasoconstrictor Agents/therapeutic use , Vertebral Artery Dissection/complications , Vertebral Artery Dissection/drug therapyABSTRACT
Cerebellar Purkinje neurons in vivo exhibit high frequency and multi-spike action potentials with transient (INaT), resurgent (INaR) and persistent (INaP) Na+ currents arising from voltage-gated Na+ channels, which play important roles in shaping the action potentials and electrical activity of these cells. However, little is known about Na+ channel expression in cultured Purkinje neurons despite the use of in vitro approaches to study these cells. Therefore, GFP-expressing Purkinje neurons isolated from transgenic mice were analysed after four weeks in culture, when, coincident with distinct axonal and dendritic morphologies, cultured Purkinje neurons exhibited dendrite-specific MAP2 expression characteristic of polarized neurons. In cell-attached patch clamp recordings, Na+ currents occurred at significantly higher frequencies and amplitudes in patches from the soma and axon than from dendrites, similar to the polarized distribution observed in vivo. INaT, INaR and INaP Na+ currents with properties similar to those observed in acutely isolated Purkinje neurons were detected in nucleated outside-out patches from cultured Purkinje cells. RT-PCR analysis detected Nav1.1, Nav1.2 and Nav1.6, but not Nav1.3, Nav1.4, Nav 1.5 or Nav1.8 Na+ channel alpha subunit gene expression in cultured Purkinje neurons, as observed in vivo. Together, the results indicate that key aspects of Na+ channel expression in mature Purkinje neurons in vivo occur in vitro.
Subject(s)
Purkinje Cells/metabolism , Sodium Channels/metabolism , Animals , Axons/metabolism , Cells, Cultured , Cerebellum/cytology , Dose-Response Relationship, Radiation , Electric Stimulation/methods , Embryo, Mammalian , Female , Gene Expression/physiology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Membrane Potentials/genetics , Membrane Potentials/physiology , Mice , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Patch-Clamp Techniques/methods , Pregnancy , Protein Subunits/genetics , Protein Subunits/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Sodium Channels/classification , Sodium Channels/geneticsABSTRACT
Niemann-Pick Type C (NPC) disease is an autosomal recessive disorder caused by mutations in either the NPC1 or HE1 genes. Hallmarks of this presently incurable disease include abnormal intracellular accumulation of cholesterol and glycosphingolipids, progressive neuropathology and neurodegeneration, and premature death. There have been increased efforts to understand the effects of NPC disease on neurons of the brain, in part due to the recent development of improved research tools and reagents, and in part due to the rapidly growing appreciation of the importance of cholesterol and lipoproteins in the brain during neuronal development, function, and degeneration. Here, we highlight fundamental aspects of neurons that appear to be affected by NPC disease, including their morphology, metabolism, intracellular transport, electrical signaling, and response to environmental factors, and suggest other potentially important areas for future investigation. This provides a framework for acquiring additional insight to this disorder and shaping new therapeutic approaches to NPC disease.