Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Overview of emerging therapies for demyelinating diseases

This paper provides an overview of autoimmune disorders of the central nervous system,specifically those caused by demyelination.We explore new research regarding potential therapeutic interventions,particularly those aimed at inducing remyelination.Remyelination is a detailed process,involving many cell types–oligodendrocyte precursor cells(OPCs),astrocytes,and microglia–and both the innate and adaptive immune systems.Our discussion of this process includes the differentiation potential of neural stem cells,the function of adult OPCs,and the impact of molecular mediators on myelin repair.Emerging therapies are also explored,with mechanisms of action including the induction of OPC differentiation,the transplantation of mesenchymal stem cells,and the use of molecular mediators.Further,we discuss current medical advancements in relation to many myelin-related disorders,including multiple sclerosis,optic neuritis,neuromyelitis optica spectrum disorder,myelin oligodendrocyte glycoprotein antibodyassociated disease,transverse myelitis,and acute disseminated encephalomyelitis.Beyond these emerging systemic therapies,we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries.Despite these aforementioned scientific advancements,this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients’quality of life.

Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease

Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.

Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement （open-loop sign）. Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement （open-ring sign） on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.

Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C

We report a case of pericarditis and chronic inflam- matory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C.The patient developed moderate weakness in the lower limbs and dyspnea.He was hospitalized for congestive heart failure.An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease.A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function.Anti-DNA antibody and anti-ds DNA IgM were positive.Neu ro logical examination revealed a symmetrical predomina ntly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution.Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance.

Conductive hearing loss in chronic inflammatory demyelinating polyneuropathy(CIDP):A case report

Chronic inflammatory demyelinating polyneuropathy(CIDP) is a progressive autoimmune disorder that targets peripheral nerves. It commonly presents with motor-predominant dysfunction and enlargement of cranial nerves. With regards to hearing loss, a few cases of sensorineural loss have been described. We present a novel case of conductive hearing loss caused by a mass on the tympanic segment of the facial nerve in the setting of CIDP.

Pathogenesis of Demyelinating Encephalopathy in Dogs with Spontaneous Acute Canine Distemper

So far, the pathogenesis of demyelination caused by canine distemper virus （CDV） in the central nervous system has remained unclear, although a lot of studies have been done extensively. To further investigate the relation of variety cells in brain to demyelination, this study was performed on 15 dogs with spontaneous acute canine distemper and 2 controls. According to anatomical relation, the brain was divided into cerebrum, cerebral stem and cerebellum. The sections with no, mild, moderate, or severe demyelinating lesions were selected respectively and stained by HE and immunohistochemistry. Immuno-localisation of CDV antigen was used to conftrm CDV infection. The brain was examined for co-localisation of the CDV antigen with either an astrocyte-specific marker, glial fibrillary acidic protein （GFAP）, or an oligodendrocyte-specific marker, galactocerebroside （GalC）. Apoptotic cell was detected by TdT-mediated nick end-labeling assay （TUNEL）. The results demonstrated that the local disturbance of blood circulation mainly included congestion, edema, thrombosis, and disseminated intravascular coagulation （DIC）. The CDV neucleocapsid protein positive reaction, metabolic disorder and apoptosis of oligodendrocytes were observed in demyelinating areas. Lots of astrocytes displayed CDV antigen-positive, especially in their process. Some of them became apoptotic cell confirmed by TUNEL staining. Fibrous astrocytes showed more intense GFAP-positive in mild and moderate demyelinating area. Some of nervous cells located in pyramidal cell layers and nucleus nervi were in degeneration, necrosis. Satellitosis, neuronophagia and apoptotic neurons were examined by hematoxylin and eosin （HE） and TUNEL staining. The results suggested that the demyelinating changes in brain tissues infected with CDV mainly related to the metabolic disorder and apoptosis of ogliodendrocytes and astrocytes; also involved with the local disturbance of blood circulation and some neuron lost.

Demyelinating polyneuropathy and lymphoplasmacytic lymphoma coexisting in 36-year-old man:A case report

BACKGROUND Lymphoplasmacytic lymphoma is a rare non-Hodgkin’s lymphoma,occurring mostly in the elderly.It develops slowly and leads to malignant proliferation of lymphoid line cells in the bone marrow,lymph nodes and spleen.It may also affect nerve roots and meninges;some patients develop sensorimotor polyneuropathy which may precede general symptoms of lymphoma.CASE SUMMARY We present a case of a 36-year-old man diagnosed in 2012 with chronic inflammatory demyelinating polyneuropathy(CIDP),then he was hospitalized in 2019 due to progressive symptoms of heart failure and significant weight loss over the previous four months.Based on clinical and laboratory findings a diagnosis of lymphoplasmacytic lymphoma was suspected and confirmed by bone marrow flow cytometry.There was no improvement in the results of laboratory tests and the patient's condition after immediate implementation of chemotherapy.Patient died on the fifth day of treatment.CONCLUSION While CIDP and malignant disease co-occurrence is rare,it should be suspected and investigated in patients with atypical neuropathy symptoms.

Tailoring of therapy for chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy （CIDP） is a treatable immune-mediated disorder, which causes in its typical form, symmetric proximal and distal weakness with large fibre sensory impairment involving the four limbs. There are currently three main first-line therapeutic options for CIDP. These consist of corticosteroids, immunoglobulins and plasma exchanges （PE） which have all been found effective in a number of trials conducted over the past several years （Van den Bergh and Rajabally, 2013）. No immunosuppressant therapy has shown benefit in CIDP, although they are utilized by many clinicians in various circumstances despite absence of an evidence base.

Tacrolimus treatment for relapsing-remitting chronic inflammatory demyelinating polyradiculoneuropathy:Two case reports

BACKGROUND This study describes the efficacy of a tacrolimus treatment regimen used to treat two patients with relapsing-remitting chronic inflammatory demyelinating polyradiculoneuropathy(CIDP).CASE SUMMARY Two patients(17-year-old female and 27-year-old male)were enrolled in the current study and were followed up for 12 mo.The first patient was administered tacrolimus(2 mg/d)for 12 mo and prednisolone(40 mg/d)for six months.The second patient was administered tacrolimus(3 mg/d)for six months.Both patients were followed up for 12 mo and the degree of recurrent weakness or normalized motor function was monitored.In addition,nerve conduction studies and tacrolimus levels were recorded.Following tacrolimus treatment,both patients showed marked improvement in clinical outcomes.In the first patient,prednisolone treatment was successfully withdrawn after six months.Sensory as well as motor nerve conduction velocities showed evident recovery following treatment.However,conduction velocities did not completely return to normal,suggesting that electrophysiological recovery can be slower than clinical recovery.CONCLUSION Neither patient exhibited any adverse effects due to the tacrolimus therapy.Therefore,tacrolimus can be effective for the treatment of patients with steroidresistant CIDP.

Spinal canal decompression for hypertrophic neuropathy of the cauda equina with chronic inflammatory demyelinating polyradiculoneuropathy:A case report

BACKGROUND Hypertrophic neuropathy of the cauda equina(HNCE)is a rare disease,especially in children.It can be caused by different etiological agents such as inflammation,tumor or hereditary factors.Currently,there is no uniform standard for clinical treatment of HNCE.Furthermore,it is unclear whether spinal canal decompression is beneficial for patients with HNCE.CASE SUMMARY We report the case of a 13-year-old boy with enlargement of the cauda equina.The onset of the disease began at the age of 6 years and was initially marked by radiating pain in the buttocks and thighs after leaning over and weakness in the lower limbs when climbing a ladder.The child did not receive any medical treatment.As the disease slowly progressed,the child needed the help of others to walk,and he had a trendelenburg gait.He underwent spinal canal decompression and a nerve biopsy during his hospital stay.A diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was made based on electrophysiological findings and pathological examination results.Immunoglobulin or hormone therapy was recommended during hospitalization,but his mother refused.After discharge,the boy’s mother helped him carry out postoperative rehabilitation training at home.His lower-limb muscle strength gradually increased,and he could stand upright and take steps.Six mo after surgery,the child was readmitted and began immunoglobulin therapy.Long-term oral steroid treatment was initiated after discharge.The movement and sensation of the lower limbs were further improved,and the boy could walk normally 1 year after surgery.CONCLUSION Spinal canal decompression can improve the clinical symptoms of HNCE caused by inflammation,even in children.When combined with specific etiological interventions,spinal cord decompression can lead to optimal outcomes.

Magnetic Resonance Imaging Characteristics of Tumefactive Demyelinating Lesions

Tumefactive demyelinating lesions (TDLs) are often misdiagnosed as brain tumors. To identify imaging characteristics of TDLs for their proper diagnosis, their differences from malignant gliomas, etc., were investigated based on 3-Tesla magnetic resonance imaging (MRI) and MR spectroscopy data that was obtained from 5 patients diagnosed with TDLs in our hospital. MfRI displayed a paraventricular lesion with a maximum diameter of ≥2 cm. Diffusion-weighted imaging (DWI) displayed a region of bright signal intensity at the margin of the lesion, and apparent diffusion coefficient (ADC) imaging displayed high signal intensity at the core of the lesion. The mass effect was mild relative to the size of the lesion, and the edema around the lesion was mild to moderate. Gadolinium-enhanced MRI displayed a characteristic open-ring sign, in which the ring of enhancement was incomplete (open towards the cortex), with the medullary vein running through the lesion, resulting in the enhancement of the surrounding area. MR spectroscopy displayed an increase in the choline peak, a decrease in the N-acetyl aspartate (NAA) peak, the presence of lactate/lipid peaks, and the presence of β, γ-glutamate-glutamine (GLX) peaks that are slightly shifted to a higher resonance frequency (2.1 - 2.4 ppm) from the NAA peak. Taken together, the following main characteristics were identified as imaging features of TDLs: bright rim on DWI, a high signal core on ADC imaging, an open-ring sign, and β, γ-GLX peaks on proton MR spectroscopy. We concluded that the key to the improvement of neurological symptoms of patients is the prompt initiation of steroid treatment following the accurate diagnosis of TDLs.

Diagnostics of Sensory Ataxia in Patients with Sensory Predominant Chronic Inflammatory Demyelinating Polyneuropathy from Republic of Sakha (Yakutia) and Krasnoyarsk Region

Materials and Methods: A group of healthy volunteers (24 people) and patients with SP-CIDP from Republic of Sakha (Yakutia) (42 people) and Krasnoyarsk region (87 people). Diagnostics Methods: Clinical neurologic, neurophysiological. Results: The results of stabilometry research of patients with SP-CIDP have revealed area expansion of pressure centre in phase EO and EC with deflection PC forward by anteropulsion type among patients with SP-CIDP from Republic of Sakha (Yakutia). Also in the Yakut group has been noted to have severer clinical course in comparison with inhabitants of Krasnoyarsk region. Conclusion: The method of computer stabilometry allows estimating objectively presence and degree of manifestation of sensitive ataxia in patients with SP-CIDP.

Intravenous transplantation of mouse embryonic stem cells attenuates demyelination in an ICR outbred mouse model of demyelinating diseases

Induction of demyelination in the central nervous system （CNS） of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. How- ever, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intrave- nous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection （mES cells-injected group） and vehicle （sham-inoculated group） were assessed and compared. The results showed that cuprizone signifi- cantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. The present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic effects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases.

Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation： a retrospective analysis of incidence, risk factors and survival

Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD） （n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following alIo-HSCT.

Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

EZH2-dependent myelination following sciatic nerve injury

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

Chinese Guidelines for the Diagnosis and Management of Tumefactive Demyelinating Lesions of Central Nervous System

Tumefactive demyelinating lesions （TDLs）,[1-3] previously named as tumor-like inflammatory demyelinating disease[4,5] or demyelinating pseudotumor,[6] are relatively special type of immune-mediated inflammatory demyelinating lesions in the central nervous system （CNS）,[7] which mainly occur within cerebrum,but rarely in spinal cord.TDLs are so named because it mimics brain tumors with such characteristics as less severe symptoms,large lesions with perilesional edema,mass effect and/or enhancement on neuroimaging,and easily misdiagnosed as brain tumors.[8,9]

Neuroimaging of corpus callosum in central nervous system demyelinating disorders

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different causes such as congenital, inflammatory, tumoral, degenerative, infectious, etc. This study reviews the most reliable neuroimaging data of human CC in central nervous system (CNS) demyelinating diseases to facilitate the understanding of different pathological entities of the CC and their role in anticipation of probable prognostic findings. After a brief description of normal anatomy and functions of CC, this review examines the most valuable findings obtained using conventional and functional magnetic resonance imaging. It also demonstrates the most well organized findings of how CC features influence prognostic factors of demyelinating disorders, which could have a great value for choosing proper therapy methods. The authors also provided a brief review of other demyelinating disorders which are primarily caused by other pathological factors other than autoimmunity. As a conclusion, the authors showed the importance of CC as an critical part of the brain, which should be explored by different methods of imaging, correspondent to clinical evaluation of CNS demyelinating disorder to widen our knowledge on pathology and clinical patterns of such disorders.

Acute demyelinating lesions with restricted diffusion in multiple sclerosis: a new variant?

Typical acute demyelinating lesions in relapsing-remitting multiple sclerosis (RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by the appearance of a bright signal on apparent diffusion coefficient (ADC) maps using diffusion weighted magnetic resonance imaging (MRI),[1] while acute ischemic stroke lesions demonstrate restricted diffusion and low signal on ADC maps.