Peripheral Nerve Disease Research Articles

Treatment of neuropsychiatric systemic lupus erythematosus: clinical challenges and future perspectives

ABSTRACT Introduction: Neuropsychiatric (NP) involvement represents an emerging frontier in systemic lupus erythematosus (SLE), posing significant challenges due to its clinical diversity and obscure pathophysiology. The authors herein discuss selected aspects in the management of NPSLE based on existing literature and our experience, aiming to facilitate routine medical care. Areas covered: Research related to diagnosis, neuroimaging, treatment and outcome is discussed, focusing on data published in PubMed during the last 5 years. Selected translational studies of clinical relevance are included. Expert opinion: Identification of NPSLE patients who may benefit from appropriate treatment can be facilitated by attribution algorithms. Immunosuppressants are typically indicated in recurrent seizures, optic neuritis, myelopathy, psychosis and peripheral nerve disease, although a low threshold is recommended for cerebrovascular disease and other NP manifestations, especially when SLE is active. With the exception of stroke with positive antiphospholipid antibodies, anti-coagulation is rarely indicated in other syndromes. Refractory NPSLE can be treated with rituximab, whereas the role of other biologics remains unknown. Advances in the fields of biomarkers, neuroimaging for brain structural, perfusion or functional abnormalities, and design of novel compounds targeting not only systemic autoimmunity but also inflammatory and regenerative pathways within the nervous system, hold promise for optimizing NPSLE management.

57-Year-Old Woman With Weakness and Word-Finding Difficulties

57-Year-Old Woman With Weakness and Word-Finding Difficulties

Immunoglobulin G4-related disease presenting with peripheral neuropathy: a case report

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition characterized by high serum IgG4 concentrations and tissue infiltration by IgG4-positive plasma cells. Reports have demonstrated that IgG4-RD affects various organs, including the pancreas, kidney, lung, thyroid, and lacrimal and salivary glands. In the nervous system, hypertrophic pachymeningitis and hypophysitis are mainly related to IgG4-RD; however, the peripheral neuropathy involvement is unusual.Case presentationWe report on a 69-year-old woman with multiple mononeuropathy, weight loss and kidney mass in the setting of IgG4-RD. Biopsies of the kidney mass showed lymphoplasmacytic sclerosing inflammation with numerous IgG4-positive plasma cells. IgG4 and IgG4/IgG ratios in the blood were elevated. The patient was treated with high dose methylprednisolone with improvement in her neuropathy.ConclusionsIgG4-RD is a relatively recently reported systemic fibrous inflammatory disease caused by the infiltration of IgG4-positive plasma cells in various organs. In the nervous system, symptomatic peripheral nerve invasion is very rare. However, as demonstrated in our case, IgG4-RD may present with primarily peripheral nerve disease.

The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases.

Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.

Spectrum, Risk Factors, and Outcomes of Neurological and Psychiatric Complications of COVID-19: A UK-Wide Cross-Sectional Surveillance Study

Background: SARS-CoV2 is associated with neurological and psychiatric complications including cerebrovascular events, encephalopathy and peripheral nerve disease. Detailed clinical data, including factors associated with recovery, is lacking, hampering prediction modelling and targeted therapeutic interventions. We studied COVID-associated neurological and psychiatric complications, to investigate the key clinical features, including those associated with outcome.Methods: This UK-wide cross-sectional surveillance study of neurological and psychiatric complications of COVID-19 in adult hospitalised patients captured detailed data on demographics/risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions, based on criteria adopted by the World Health Organisation, were used, with cross-specialty independent adjudication for discrepant cases. Patients meeting multiple clinical case definitions were identified. Cases of stroke were compared to normative data during the equivalent time-period prior to the pandemic. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome.Findings: 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy not meeting delirium criteria; and peripheral nerve-disorders (41, 15%). 27% of cerebrovascular events occurred in patients 60 years old, the younger patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and more frequently had systemic thrombotic events. Nevertheless, in both younger and older stroke cases there was an association with conventional, modifiable, cerebrovascular risk factors. The timing of neurological presentation varied between disease groups. In 34 cases (13%), clinical case definitions overlapped, and these cases were more likely to require intensive care and ventilation. Regardless of clinical case definition, older age, a higher pre-COVID-19 frailty score, and a high admission white cell count independently associated with a poor outcome. Limited recovery was most common for those with cerebrovascular events. Interpretation: COVID-19 is associated with a broad spectrum of presentations throughout the nervous system, at varied time points relative to respiratory disease. Outcomes vary between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of age and frailty. A severe encephalopathy occurs after COVID-19 and is associated with requiring intensive care and ventilation. COVID-19 is associated with large and multi-vessel stroke in young people, often with non-CNS thrombotic disease and requires further study. Nevertheless, conventional, modifiable risk factors were associated with stroke, even in younger people, suggesting the potential for public health intervention for this and future pandemics. These clinical data should be combined with blood and neuroimaging biomarkers so that patients can be stratified to targeted existing or novel therapeutics.

Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture.

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion (DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates (T-DRG) versus three-dimensional collagen hydrogels (C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis- and myelination-related genes were highly expressed in C-DRG, while epithelial-mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B (S100B) and lower α-smooth muscle actin (α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly formed nerve bundles were able to grow along the existing Schwann cells in C-DRG. These results suggest that C-DRG may be a promising in vitro culture model, with better nerve growth and anti-apoptotic ability, quiescent Schwann cells, and higher viability. Results from this study provide a reference for the construction, storage, and transportation of tissue-engineered nerves. The study was approved by the Ethics Committee of Aier School of Ophthalmology, Central South University, China (approval No. 2020-IRB16), on March 15, 2020.

Ficus carica L. Attenuates Denervated Skeletal Muscle Atrophy via PPARα/NF-κB Pathway.

Treatment options for denervated skeletal muscle atrophy are limited, in part because the underlying molecular mechanisms are not well understood. Unlike previous transcriptomics studies conducted in rodent models of peripheral nerve injury, in the present study, we performed high-throughput sequencing with denervated atrophic biceps muscle and normal (non-denervated) sternocleidomastoid muscle samples obtained from four brachial plexus injury (BPI) patients. We also investigated whether Ficus carica L. (FCL.) extract can suppress denervated muscle atrophy in a mouse model, along with the mechanism of action. We identified 1471 genes that were differentially expressed between clinical specimens of atrophic and normal muscle, including 771 that were downregulated and 700 that were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed genes were mainly enriched in the GO terms “structural constituent of muscle,” “Z disc,” “M band,” and “striated muscle contraction,” as well as “Cell adhesion molecules,” “Glycolysis/Gluconeogenesis,” “Peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway,” and “P53 signaling pathway.” In experiments using mice, the reduction in wet weight and myofiber diameter in denervated muscle was improved by FCL. extract compared to saline administration, which was accompanied by downregulation of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Moreover, although both denervated groups showed increased nuclear factor (NF)-κB activation and PPARα expression, the degree of NF-κB activation was lower while PPARα and inhibitor of NF-κB IκBα expression was higher in FCL. extract-treated mice. Thus, FCL. extract suppresses denervation-induced inflammation and attenuates muscle atrophy by enhancing PPARα expression and inhibiting NF-κB activation. These findings suggest that FCL. extract has therapeutic potential for preventing denervation-induced muscle atrophy caused by peripheral nerve injury or disease.

Polyneuropathy in POEMS Syndrome

A rare version of paraproteinemic hemablastosis, with the onset characterized by Peripheral Nerve Disease, is POEMS- syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin Changes). In the foreground of the clinical picture of this oncohematological disease is progressive sensorimotor polyneuropathy, which is the reason for the primary reference to a neurologist long before the provision of specialized hematological care. The article provides an overview of recent scientific publications devoted to this disease. Its pathogenetic mechanisms are discussed, as well as the basis of endothelial growth factor. The authors present their own clinical observation of a 62-year-old patient. The onset of the disease was characterized by polyneuropathy accompanied by changes in the M-protein index, organomegaly in the absence of bone-destructive changes, which made the diagnosis difficult. Additional clinical signs included fever, edema (ascites, exudative pleurisy), and hypoproteinemia, changes in peripheral blood (moderate leukocytosis with a decrease in the level of erythrocytes and platelets, which is atypical), kidney and cardiovascular damage. Despite the specific therapy, the patient’s condition was complicated by the development of infectious complications and was fatal. This clinical observation illustrates the need for a careful differential search for a possible cause of non-polyneuropathy of unknown genesis.

Musculoskeletal disorders and working risk factors.

The authors evaluate situation in the field of musculoskeletal disorders (MSDs) and working risk factors in the Czech Republic. Analysis of selected data from the Czech National Registry of Occupational Diseases during 2008-2018, description of criteria for recognition of occupational MSDs and risk factors associated with MSDs. 6,152 cases of 6 selected recognized occupational musculoskeletal diseases represent 47% of all recognized occupational diseases. The main proportion formed diseases of peripheral nerves in the extremities in terms of compressive neuropathies due to long-term and stereotyped overload, diseases of tendons, tendon capsules or insertions of muscles or joints in the extremities due to long-term and stereotyped overload and diseases of peripheral nerves in the upper extremities in terms of ischaemic and compressive neuropathies due to work with vibrating tools and devices. The authors discussed decreasing trend of the exposure time in three main diagnoses and association of the incidence of MSDs with the risky work related to overload of the musculoskeletal system of the upper extremities. Important factors for the prevention of MSDs are directly related to the technical provision of production, the organization of work and the regime of work and rest, the length of working hours and the setting of production standards, and generally to the work related stress.

Lactate Transporters Mediate Glia-Neuron Metabolic Crosstalk in Homeostasis and Disease.

Research over the last couple of decades has provided novel insights into lactate neurobiology and the implications of lactate transport-driven neuroenergetics in health and diseases of peripheral nerve and the brain. The expression pattern of lactate transporters in glia and neurons has now been described, though notable controversies and discrepancies remain. Importantly, down- and up-regulation experiments are underway to better understand the function of these transporters in different systems. Lactate transporters in peripheral nerves are important for maintenance of axon and myelin integrity, motor end-plate integrity, the development of diabetic peripheral neuropathy (DPN), and the functional recovery following nerve injuries. Similarly, brain energy metabolism and functions ranging from development to synaptic plasticity to axonal integrity are also dependent on lactate transport primarily between glia and neurons. This review is focused on critically analysing the expression pattern and the functions of lactate transporters in peripheral nerves and the brain and highlighting their role in glia-neuron metabolic crosstalk in physiological and pathological conditions.

Effects of diabetes on apoptosis and mitosis in rat hippocampus

ABSTRACT Diabetes contributes to neurological dysfunction including peripheral nerve diseases, stroke and dementia. We investigated the effects of diabetes on apoptosis and mitosis in the hippocampal CA1 region. Rats were given diabetes by injection of streptozotocin (STZ). The mass and blood glucose levels of the rats were measured until day 7 of the experiment. The loss of mass index was approximately 10%, and the diabetogenic index was approximately 330% between nondiabetic and diabetic groups. We investigated caspase-3, caspase-7 and Ki 67 levels immunohistochemically for mitotic activity, the TUNEL method for apoptosis and GFAP for astrocyte cell density in the hippocampal CA1 region. We found that apoptotic cells and the number of astrocytes and mitotic activity in the diabetic group were increased significantly compared to controls. Diabetes stimulates apoptosis and promotes cell proliferation in the hippocampal CA1 region, which may impair its homeostasis and function.

The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement

Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle diseases. Over the years, numerous studies have pointed to protein homeostasis as a crucial factor in the development of these fatal diseases. The ubiquitin–proteasome system (UPS) plays a fundamental role in maintaining protein homeostasis, being involved in protein degradation, among other cellular functions. Through a cascade of enzymatic reactions, proteins are ubiquitinated, tagged, and translocated to the proteasome to be degraded. Within the ubiquitin system, we can find three main groups of enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin–protein ligases). Only the ubiquitinated proteins with specific chain linkages (such as K48) will be degraded by the UPS. In this review, we describe the relevance of this system in NMDs, summarizing the UPS proteins that have been involved in pathological conditions and neuromuscular disorders, such as Spinal Muscular Atrophy (SMA), Charcot–Marie–Tooth disease (CMT), or Duchenne Muscular Dystrophy (DMD), among others. A better knowledge of the processes involved in the maintenance of proteostasis may pave the way for future progress in neuromuscular disorder studies and treatments.

Lupus Vasculitis.

The purpose of this manuscript is to review the most recent literature pertinent to the presence of vasculitis in patients with systemic lupus erythematosus (SLE), including previously published landmark articles and studies and to update the different clinical and diagnostic aspects of vasculitic manifestations in patients with this important autoimmune disorder. As a multisystem autoimmune disease, systemic lupus may attack practically any organ system in the human body. Even though vasculitis is not the most common presentation or pathogenic mechanism of disease, it frequently causes significant morbidity and mortality in patients with SLE. The most common manifestation of lupus vasculitis is cutaneous involvement; visceral involvement is less common but causes severe disease; it may occur in different areas including central nervous system, peripheral nervous system, gastrointestinal system, kidneys, lungs and even retina. Recent findings regarding the pathogenesis of lupus CNS and peripheral nerve disease, and vascular injury in lupus nephritis are reviewed as well. Vasculitis is an uncommon but serious manifestation of SLE; it may involve different organ systems and present in a wide variety of clinical syndromes, and thus the importance of its recognition and early diagnosis by physicians who deal with this disease, in order to start prompt and aggressive therapy when indicated.

Muscular pathological features in patients with Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is a kind of autoimmune disease of the neuromuscular junction that is often misdiagnosed as a peripheral nerve disease or myopathy. For some difficult cases, muscle biopsy examination is useful for differential diagnosis. However, studies about the pathological findings of LEMS patients are rare, especially of patients who were diagnosed with small cell lung carcinoma (SCLC). This study aimed to describe several pathological muscle features in patients with LEMS associated with SCLC. The 5 patients enrolled in this study were diagnosed with LEMS associated with SCLC by clinical manifestation, electromyography, and lung biopsy. Muscle biopsies were performed for the patients, and enzyme histopathology was assessed. The hematoxylin and eosin (H & E) stain showed different sizes of fibers, and the shape of atrophic fibers were angular or polygonal. The adenosine triphosphatase (ATPase) stain demonstrated that the majority of atrophic fibers were type II. Type II fiber predominance was observed in case 1 and case 5. Also, scattered muscle fiber necrosis was shown in case 3. Type II fiber atrophy and type II fiber predominance may often be found in patients with LEMS associated with SCLC. Also, scattered fiber necrosis may appear in this disease.

High-Resolution Nerve Ultrasound to Assess Nerve Echogenicity, Fascicular Count, and Cross-Sectional Area Using Semiautomated Analysis.

Little is known about echogenicity and fascicular structure observed in high-resolution nerve ultrasound (HRUS) in both healthy subjects and patients with peripheral nerve disease. The aim of this study was to evaluate the reliability of echogenicity, fascicle count, and fascicle size analysis, to create standard values and compare these parameters to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Median, ulnar, radial, tibial, and fibular nerve of 79 healthy subjects and patients were scanned by one examiner using HRUS. Image analysis regarding echogenicity, fascicle count, and fascicle cross-sectional area (CSA) was performed by two independent raters semiautomatically using ImageJ. Pearson correlation coefficient r reflected interrater reliability (IR), and intraclass correlation coefficient (ICC) determined intrarater reliability (IAR). Results of healthy subjects were compared to 20 patients with CIDP by analysis of variance. IR was very good for echogenicity (r = .9) and good for fascicle count and size of the largest fascicle (r = .64/.56). IAR was very good for all three parameters (ICC = .9/.83/.74). Healthy subjects had a wide range of values. CIDP patients were in range of healthy subjects. Clinically progressive CIDP patients (defined as an increase in Overall Disability Sum Score by ≥1 point) had a lower fraction of black than healthy controls and stable CIDP patients (P < .001). Semiautomated evaluation of echogenicity, fascicle count, and fascicle CSA is reliable. Cutoff values to differentiate between healthy persons and CIDP do not exist. Echogenicity is useful for detecting clinically progressive CIDP patients and should be used in clinical context or intraindividual course.

Emerging technologies in neuromuscular ultrasound.

Neuromuscular ultrasound is an accepted and valuable element in the evaluation of peripheral nerve and muscle disease. However, ultrasound has several limitations to consider, including operator dependency and lack of a viable contrast agent. Fortunately, new technological advances show promise in resolving these issues. Ultra-high resolution ultrasound enables imaging of the nerve at the fascicular level. Shear wave elastography imaging can provide measures of tissue stiffness that can act as a surrogate measure of nerve and muscle health. Photoacoustic imaging may overcome neuromuscular ultrasound's current lack of contrast agents to detect inflammation and other functional changes within nerve and muscle, while artificial intelligence stands to address operator dependency and improve diagnostic imaging. The basic principles of each of these technologies are discussed along with current research and potential future applications in neuromuscular imaging.

Ultrasonogram morphology of tibial nerve in type 2 diabetes mellitus patients and its association with HbA1c

Background: In the recent years High-resolution ultrasonography (HRUS) has geared up as a new diagnostic tool in the work-up of peripheral nerve diseases. As most of the peripheral nerves run a superficial course over a long tract, especially in the arms and legs which could be easily visualised using ultrasonogram. Aim: To assess the morphology of tibial nerve using ultrasonogram and correlate it with the glycemic score among the diabetes mellitus patients Methodology: A cross-sectional study was conducted for a period of 6 months in the radiology department. A non-random quota sampling was followed to select the sample size and based on that 50 subjects were taken as our study sample. All known type II diabetes patients with a history of peripheral neuropathy were included as our study subjects. Ultrasonography was performed for all study subjects with USG Samsung Accuvix XG Linear probe 5-12 MHz. The maximum thickness of the nerve fascicle was calculated by the largest antero-posterior dimension and the lateral dimension of the largest hypoechoic area in the short axis view of the tibial nerve. Results: Correlation between the HbA1C levels and the maximum thickness of nerve fascicles measurements shows that there was statistically significant positive correlation exist between the two parameters, as the levels of HbA1c increases the thickness of nerve fascicles also increases and similarly a statistical significant association was observed between the duration of diabetes and maximum thickness of nerve fascicles. Conclusion: Ultrasonography is an excellent diagnostic tool for detecting morphological changes in the tibial nerves in diabetic patients.

ЕФЕКТИВНІСТЬ ЗАСТОСУВАННЯ РЕАБІЛІТАЦІЙНИХ ЗАХОДІВ ПІСЛЯ НЕЙРОХІРУРГІЧНОГО ВІДНОВЛЕННЯ ЦІЛІСНОСТІ ПОШКОДЖЕНИХ ПЕРИФЕРИЧНИХ НЕРВІВ ВЕРХНЬОЇ КІНЦІВКИ

Аbstract. Traumatic neuropathies are the most common group of peripheral nerve diseases. The article considers the effectiveness of rehabilitation measures after neurosurgical restoration of the integrity of the upper extremity damaged peripheral nerves. Objective. To evaluate the effectiveness of the technology of rehabilitation measures in patients after neurosurgical restoration of the integrity of the upper extremity damaged peripheral nerves. Methods. Theoretical (analysis and generalization of data from literature sources and the Internet), anthropometric (goniometry, dynamometry), electroneuromyography (ENMG). Results. Initial examination demonstrated a decrease in the range of motions in the joints and muscle strength of the affected limb im most patients. According to the results of ENMG, there was a decrease in the rate of excitation propagation of both motor and sensory responses in all damaged nerves and the amplitude of the M-response, which indicated nervous tissue injury. Rehabilitation technology in the main group of patients included means and methods of kinesitherapy, exercises in water, massage, orthoses, kinesitherapy, PNF technique, neurodynamic techniques. To restore the grips of the injured hand and activity in everyday life exercises on ergotherapy simulator ARAT, mirror therapy, CIMT-therapy were used. Standard rehabilitation measures were applied for patients of the control group. Upon re-examination as a result of modern rehabilitation measures, we found a significant positive dynamics of anthropometric and neurophysiological parameters in patients of both groups, but in the main group most of these indices were significantly better. The proposed technology of rehabilitation measures in patients with damage to the peripheral nerves of the upper extremities allows to optimize the appointment of physical therapy and ergotherapy aimed at restoring lost limb functions.

Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy.

Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, including multiple forms of cancer, and represents an emerging therapeutic target. Successful development of such therapeutics requires a detailed understanding of potential on-target toxicities. Here, we identify autosomal dominant mutations of the canonical Notch ligand Jagged1 (or JAG1) as a cause of peripheral nerve disease in 2 unrelated families with the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2 (CMT2). Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Our studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Together, our findings highlight a critical role for JAG1 in maintaining peripheral nerve integrity, particularly in the recurrent laryngeal nerve, and provide a basis for the evaluation of peripheral neuropathy as part of the clinical development of Notch pathway-modulating therapeutics.

Diagnosis and treatment progress of Guillain-Barré syndrome

Guillain-Barre syndrome(GBS)is a most common nervous system disease that may cause acute delayed paralysis. The findings of latest researches showed that GBS includes a group of autoimmunity related peripheral nervous disease presenting varied clinical phenotype and pathophysiological changes. The clinical top priority to choose the treatments were intravenous infusion of gamma globulin and plasma exchange. With the rapidly deepening of pathological mechanisms of GBS, new treatment approaches will appearto serve in clinical care.