Demyelination In Peripheral Nervous System Research Articles

Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.

CLINICO- ELECTROPHYSIOLOGICAL AND CSF PROFILE AND PREDICTORS OF FUNCTIONAL OUTCOME IN GUILLAINE-BARRE SYNDROME- A PROSPECTIVE STUDY

BACKGROUND Guillain-Barre syndrome (GBS) is a rare, immune mediated disorder which is associated with demyelination of peripheral nervous system and progressive muscle weakness, with an annual global incidence of approximately 1–2 per 100,000 person-years. GBS has an unpredictable clinical course with up to 30% of patients requiring assisted ventilation during the course of their illness. Recent advances in the eld of critical care has successfully improved the outcome of GBS. Successful management mandates anticipation, prompt recognition of modiable risk factors and optimal treatment of neuromuscular respiratory failure in GBS. There is limited Indian data with regards to the early determinants and outcome of severely affected GBS patients. Knowledge of early predictors can substantially improve patient care and provides essential data for triage at an early stage in the course of the illness. OBJECTIVE 1. To study the clinical, electrophysiological prole, progression and outcome of GBS in a tertiary care hospital. 2. To determine the factors associated with the poor functional outcome, including the need for mechanical ventilation. MATERIALS AND METHODS This was a single centre, prospective study with 50 patients with GB syndrome, conducted from from 1st June 2021 to 30th May 2022 for a period of 1 year at Gauhati Medical College and Hospital. Their clinical, electrophysiological, CSF parameters were analysed. Hughes grading, EGRIS, mEGOS, MRC sum score were used. Any clinical deterioration and need for mechanical ventilation were noted carefully. Patients were followed up at 3 months and 6 months at assess their outcome. The mean age of the patients was 30.5 RESULTS years with a male female ratio of 1.3:1. AIDP was the most prevalent subtype found in 23(46%) patients followed by AMAN in 14(28%), AMSAN in 9(18%) and 4(8%) cases were unclassied. 32(64%) had severe disease with Hughes score ≥ 4 and 28(56%) had MRC score <40 at presentation. Respiratory distress was found in 17(34%) of patients, and out of which 10(20%) required mechanical ventilation. During the study 2(4%) patients died of complications. At 3 months, 30(60%) patients had complete recovery, 12(24%) had partial recovery and 6(12%) had poor recovery. At 6 months, 35(70%) had good recovery, 9(18%) had partial recovery and 4(8%) had poor recovery. Delayed CONCLUSION presentation, early peak of illness, prolonged Hospital stay, bulbar weakness, neck exor weakness, bilateral facial weakness, quadriparesis, respiratory distress, need for mechanical ventilation, autonomic dysfunction; high Hughes grading, low average single breath count along with high EGRIS, mEGOS, MRC sum score, high CSF protein, albumin-cytological dissociation, presence of F-wave abnormalities and Non stimulable nerves or Inexcitable nerves on NCS, AMAN subtype and systemic complications are associated with poor outcome. The overall outcome of GBS is favourable.

Intravenous immunoglobulin preparations attenuate lysolecithin-induced peripheral demyelination in mice and comprise anti-large myelin protein zero antibody.

Intravenous immunoglobulin (IVIg) has been used to treat inflammatory demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and multifocal motor neuropathy. Despite studies demonstrating the clinical effectiveness of IVIg, the mechanisms underlying its effects remain to be elucidated in detail. Herein, we examined the effects of IVIg on lysolecithin-induced demyelination of the sciatic nerve in a mouse model. Mice -administered with IVIg 1 and 3 days post-injection (dpi) of lysolecithin -exhibited a significantly decreased demyelination area at 7 dpi. Immunoblotting analysis using two different preparations revealed that IVIg reacted with a 36-kDa membrane glycoprotein in the sciatic nerve. Subsequent analyses of peptide absorption identified the protein as a myelin protein in the peripheral nervous system (PNS) known as large myelin protein zero (L-MPZ). Moreover, injected IVIg penetrated the demyelinating lesion, leading to deposition on L-MPZ in the myelin debris. These results indicate that IVIg may modulate PNS demyelination, possibly by binding to L-MPZ on myelin debris.

Combined central and peripheral demyelination: a case report

Overlapping central nervous system (CNS) and peripheral nervous system (PNS) demyelination is a rare clinical entity, more frequently seen in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multiple sclerosis (MS). This case report showcases a patient with atypical CIDP and CNS demyelination lesions. Demographic data, disease course, treatment responsiveness, neurological examination, laboratory tests, nerve conduction studies (NCS), and brain and spinal cord MRI were registered. The case highlights the difficulty of diagnosis establishment and treatment selection, given the atypical course of the disease and limited answers to the indicated therapies. The data from our report suggest that specific and widely available immunological targets are necessary for diagnosing combined central and peripheral demyelination cases appropriately. The association of different immunotherapeutic agents may be necessary to induce and maintain disease remission.

Nangs, balloons and crackers: Recreational nitrous oxide neurotoxicity.

Nitrous oxide is a colourless, odourless gas that has been used in medicine for more than 150 years for its anaesthetic and analgesic properties. Its first recorded use as a recreational drug was in early 19th century Britain at 'laughing gas parties', where it was used to provide short-lived euphoria to the bored upper class. A recent resurgence of its abuse among Australian youth has led to marked neurological morbidity. The aim of this article is to provide an overview of the clinical presentation, differential diagnosis, investigation and treatment of patients presenting with neurotoxicity due to recreational nitrous oxide abuse. Nitrous oxide exerts its neurotoxicity through vitamin B12 inactivation, which disrupts myelin sheath maintenance, leading to peripheral and central nervous system demyelination. Importantly, patients often present with non-specific sensorimotor signs and symptoms with normal serum vitamin B12 levels. Early recognition and treatment are crucial to limit long-term neurological sequelae.

An intriguing case of combined central and peripheral demyelination

It is extremely rare to see combined central and peripheral nervous system demyelination. We are reporting this case of central demyelination in a case of multifocal acquired demyelinating sensorimotor neuropathy (MADSAM). After thorough review of literature, it is the first case report from India.

Combined central and peripheral nervous system demyelination: an unusual presentation of MOG antibody disorder (2954)

Combined central and peripheral nervous system demyelination: an unusual presentation of MOG antibody disorder (2954)

Research progress in nervous system damage caused by SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major outbreak in the world. SARS-CoV-2 infection can not only involve in the respiratory system, but also cause severe nervous system damage. Studies have shown that SRAS-CoV-2 can invade the nervous system through hematogenous and transneuronal pathways, and may cause nervous system damage in patients with COVID-19 by inhibiting cellular immunity, hypoxemia, inflammation, inducing neuronal degeneration and apoptosis, and angiotensin converting enzyme 2 (ACE2) mechanism. It can lead to intracranial infection, toxic encephalopathy, acute cerebrovascular disease, muscle damage, peripheral nervous system injury, acute myelitis, demyelination disease or other nervous system diseases.

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain\u2013Barr\xe9 syndrome

Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

Krabbe disease successfully treated via monotherapy of intrathecal gene therapy.

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased GALC enzyme activity, normalized psychosine concentration, improved myelination, and attenuated inflammation in both the CNS and PNS. Moreover, AAV-mediated therapy successfully prevented clinical neurological dysfunction, allowing treated dogs to live beyond 2.5 years of age, more than 7 times longer than untreated dogs. Furthermore, we found that a 5-fold lower dose resulted in an attenuated form of disease, indicating that sufficient dosing is critical. Finally, postsymptomatic therapy with high-dose AAV9 also significantly extended lifespan, signifying a treatment option for patients for whom HSCT is not applicable. If translatable to patients, these findings would improve the outcomes of patients treated either pre- or postsymptomatically.

Electroneurography and Advanced Neuroimaging Profile in Pediatric-onset Metachromatic Leukodystrophy.

Context:Metachromatic leukodystrophy (MLD) is a rare autosomal-recessive disorder characterized by demyelination of central and peripheral nervous system. There is scarcity of literature on the electrophysiological aspects of peripheral nerves and the advanced neuroimaging findings in MLD.Aim:The aim was to study the nerve conduction parameters and advanced neuroimaging findings in patients with MLD.Materials and Methods:This study is a retrospective analysis conducted, between 2005 and 2016, of 12 patients who had biochemical, histopathological, or genetic confirmation of MLD and disease onset before 18 years of age. The clinical, electroneurography, and the advanced neuroimaging findings were reviewed and analyzed.Statistical Analysis:The data were presented as percentages or mean ± standard deviation as defined appropriate for qualitative and quantitative variables.Results:Mean age of onset was 4.84 (±4.60) years and seven patients were males. Eight patients had juvenile MLD and four had late infantile MLD. Clinical presentation of psychomotor regression was more common in infantile MLD (75%), whereas gait difficulty (62.5%) and cognitive impairment (37.5%) were more frequent in juvenile MLD. Nerve conduction study (NCS) revealed diffuse demyelinating sensorimotor peripheral neuropathy in 9 (75%) patients. One patient had a rare presentation with conduction blocks in multiple nerves with contrast enhancement of cauda equina. Diffusion restriction involving periventricular and central white matter was seen in five patients and bilateral globus pallidi blooming was noted in three patients.Conclusion:This study highlights the utility of NCS and advanced magnetic resonance imaging sequences in the diagnosis of MLD.

Acute combined central and peripheral nervous system demyelination: a case report

Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) are demyelinating neurologic disorders with different target organs. Although they share similar pathogenetic mechanism, reports of simultaneous occurrence of the 2 disorders are rare. A 2 year 6 month old girl visited our hospital for fever, cough, and general weakness. Although the muscle power of extremities showed mild weakness and voiding difficulty, initial deep tendon reflex of both knees and ankles was normal. A nerve conduction study to evaluate the weakness revealed the absence of F waves. Cerebrospinal fluid analysis demonstrated pleocytosis with lymphocyte predominance and elevated protein levels. Magnetic resonance imaging showed abnormal T2 hyperintensity in pons, medulla and spinal cord. Serum anti-GD1b antibody was positive. Based on clinical findings, laboratory findings, nerve conduction study, and neuroimaging, the diagnosis of GBS and ADEM was made. This is the first case of GBS accompanied by ADEM in Korea.

AAVrh10 Gene Therapy Ameliorates Central and Peripheral Nervous System Disease in Canine Globoid Cell Leukodystrophy (Krabbe Disease).

Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase. Most commonly, deficits of galactosylceramidase result in widespread central and peripheral nervous system demyelination and death in affected infants typically by 2 years of age. Hematopoietic stem-cell transplantation is the current standard of care in children diagnosed prior to symptom onset. However, disease correction is incomplete. Herein, the first adeno-associated virus (AAV) gene therapy experiments are presented in a naturally occurring canine model of GLD that closely recapitulates the clinical disease progression, neuropathological alterations, and biochemical abnormalities observed in human patients. Adapted from studies in twitcher mice, GLD dogs were treated by combination intravenous and intracerebroventricular injections of AAVrh10 to target both the peripheral and central nervous systems. Combination of intravenous and intracerebroventricular AAV gene therapy had a clear dose response and resulted in delayed onset of clinical signs, extended life-span, correction of biochemical defects, and attenuation of neuropathology. For the first time, therapeutic effect has been established in the canine model of GLD by targeting both peripheral and central nervous system impairments with potential clinical implications for GLD patients.

Chapter 2 - HIV neuropathology

Primary human immunodeficiency virus (HIV) neuropathologies can affect all levels of the neuraxis and occur in all stages of natural history disease. Some, like HIV encephalitis, HIV myelitis, and diffuse infiltrative lymphocytosis of peripheral nerve, reflect productive infection of the nervous system; others, like vacuolar myelopathy, distal symmetric polyneuropathy, and central and peripheral nervous system demyelination, are not clearly related to regional viral replication, and reflect more complex cascades of dysregulated host immunity and metabolic dysfunction. In pediatric patients, the spectrum of neuropathology is altered by the impacts of HIV on a developing nervous system, with microcephaly, abundant brain mineralization, and corticospinal tract degeneration as examples of this unique interaction. With efficacious therapies, CD8 T-cell encephalitis is emerging as a significant entity; often this is clinically recognized as immune reconstitution inflammatory syndrome, but has also been described in the context of viral escape and treatment interruption. The relationship of HIV neuropathology to clinical symptoms is sometimes straightforward, and sometimes mysterious, as individuals can manifest significant deficits in the absence of discrete lesions. However, at all stages of the natural history disease, neuroinflammation is abundant, and critical to the generation of clinical abnormality. Neuropathologic and neurobiologic investigations will be central to understanding HIV nervous system disorders in the era of efficacious therapies.

Alterations of plasma concentrations of lipophilic antioxidants are associated with Guillain-Barre syndrome

BackgroundGuillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy resulting in demyelination in peripheral nervous system. Myelin enriched in lipids is easily oxidized by reactive oxygen species during inflammation. Oxidative stress and lipophilic anti-oxidative capacities in GBS patients have not been fully explored. To evaluate the redox status of GBS patients, we measured malondialdehyde (MDA), myeloperoxidase (MPO), lipophilic antioxidants, and tocopherols concentrations in plasma from GBS patients and age-matched healthy controls. ResultsConcentrations of γ-tocopherol and δ-tocopherol decreased significantly, and α-carotene significantly increased in GBS patients compared to healthy controls. However, no significant changes in MDA and MPO concentrations were detected. In GBS patients, the γ-tocopherol concentration correlated positively with concentrations of δ-tocopherol, α-tocopherol, lutein, Q10, and γ-CEHC, respectively. Similarly, the δ-tocopherol concentration correlated positively with γ-tocopherol, α-tocopherol, lutein, Q10, δ-CEHC, and γ-CEHC concentrations, respectively. The receiver operating characteristics curve analysis showed that γ-tocopherol may serve as a good predictor for GBS. ConclusionsDiminished lipophilic antioxidant defense, mainly γ-tocopherol and δ-tocopherol, in GBS patients accounting for their lowered resistance to reactive oxygen species is probably associated with pathogenesis of GBS, and potentially useful for the development of therapeutic strategies.

Combined central and peripheral nervous system demyelination: a case report

Combined central and peripheral nervous system demyelination: a case report

Fulminant Central Plus Peripheral Nervous System Demyelination without Antibodies to Neurofascin.

Combined central and peripheral nervous system demyelination is a rare and poorly described phenomenon. Recently, anti-neurofascin antibodies were reported to be positive in 86% of these patients in a Japanese cohort. Yet, there seems to be a clinical, radiological, and serological heterogeneity among these patients. In this report, our aim is to describe characteristics of our patients with this entity and compare with others in the literature. We report clinical, electrophysiological, radiological, and laboratory characteristics of five patients with both multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy from our institutional database containing 1890 MS patients. Three patients presented with extensive, active demyelination of both central nervous system and peripheral nervous system with hypertrophic peripheral nerves. Plexuses, trunks, division and cords were involved in the process. Oligoclonal band was negative. Conduction block was not detected. Corticosteroid treatment was not adequate. Others had a slowly progressive clinical course. Serum anti-neurofascin antibody was negative. Review of the literature revealed similar cases with active disease, early-onset hypertrophic peripheral nerves, and central demyelination, in addition to other cases with an insidious course. Patients with combined central and peripheral demyelination form a spectrum. Some patients may have an antibody-mediated syndrome with or without anti-neurofascin antibodies and others seem to represent a coincidence.

Intensive care management of Guillain-Barre syndrome: A retrospective outcome study and review of literature

Abstract Introduction: Guillain-Barre syndrome (GBS) is an immune mediated disorder which is associated with demyelination of peripheral nervous system and progressive muscle weakness. Severely affected patients have respiratory dysfunction and may need ventilatory support which can cause significant morbidity and mortality. There is limited Indian data with regards to the outcome of severely affected GBS patients. The present study reflects the intensive care management of severely affected GBS patients at neurological centre of a tertiary care institute of India. Materials and Methods: The study was designed to retrospectively review the patient records who were admitted to neurological intensive care unit (ICU) of AIIMS, New Delhi. The epidemiology, clinical features, course of management and outcome of GBS patients admitted between April 2000 to December 2005 were recorded and analysed. Results: The data of 59 patients were available for inclusion in the study. The mean age of patients admitted to neurological ICU was 35 years with male preponderance. Ventilatory failure was the most common indication for ICU admission. 95% patients required ventilatory support for a mean duration of 30 days. The mortality data included 60 patients and 13 patients died during the course of management. Conclusions: The present study indicates that severely affected GBS patients may need prolonged mechanical ventilation. Despite management in a specialized neurological ICU the mortality can be as high as 21%.

Central and Peripheral Nervous System Demyelination Following Mycoplasma Pneumonia Infection With Review of Literature

Central and Peripheral Nervous System Demyelination Following Mycoplasma Pneumonia Infection With Review of Literature

Perioperative Management of a Recovered Case of Guillain Barre Syndrome for Emergency LSCS : Anaesthetic Implications

Guillain Barre Syndrome (GBS) is an acute post-infectious polyneuropathy of autoimmune nature, charactesrised by demyelination of peripheral nervous system and rapidly progressive paralysis. GBS is rare entity and possibly even rarer in pregnancies with incidence of 1.7 lakh pregnancies. The course of GBS is self-limiting, generally with excellent prognosis. 85 percent of patients with GBS obtain a good to full recovery while 3-5% experience recurrent or chronic neuropathy. We present a case of 28 yr female known case of GBS, recovered completely with IV immunoglobulins, posted for emergency LSCS in view of severe fetal bradycardia. Our patient was given general anaesthesia considering emergency nature of surgery. The literature search for the anaesthetic management of such a case revealed no consensus, which prompted us to report this case.