Immune-mediated Polyneuropathy Research Articles

O-28 Simulated differential sensitivity of motor and sensory nerves for conduction block in immune-mediated neuropathies

Background Immune-mediated polyneuropathies affect myelinated nerve fibers, resulting in conduction slowing or block, with selective involvement of sensory and motor axons. The underlying mechanisms are not well understood. We studied the impact of putative mechanisms by focusing on nodal and paranodal dysfunction on saltatory conduction in a longitudinal myelinated axon model. Materials and methods We extended our longitudinal axon model, which consisted of 41 nodes of Ranvier, with biophysical characteristics unique for human myelinated motor or sensory axons. We studied the effects of impaired nodal sodium channel conductance, paranodal myelin loop detachment by reducing paranodal seal resistance, and their interaction on saltatory conduction in the nine middle nodes and surrounding paranodes. Results Physiological motor and sensory conduction velocities were approximately 48 m/s and 50 m/s, respectively. Progressive conduction slowing was observed when reducing maximum sodium channel conductance and reducing paranodal seal resistance. Conduction blocks eventually occurred at a 75% (motor) and 78% (sensory) reduction in maximum sodium channel conductance and at a 87% (motor) and 89% (sensory) reduction in paranodal seal resistance. A boundary of block emerged representing the severity levels where both interacting mechanisms induced a conduction block. Conclusion Using our longitudinal myelinated motor and sensory axon model, simulations support the view that biophysical differences between motor and sensory axons potentially contribute to a differential susceptibility for development of a conduction block in immune-mediated polyneuropathies.

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review.

Objective Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients' quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients' QoL. Methodology A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in painful PN. Information was extracted regarding prevalence, demographics, and response to treatment where relevant. Results We identified 66 articles eligible for inclusion. The vast majority of studies (n=47) focused on patients with diabetic PN. Other aetiologies of painful PN where QoL has been studied to date include gluten, immune-mediated, HIV, chemotherapy-induced, and chronic idiopathic axonal polyneuropathy. Pharmacological treatment is the mainstay in managing pain and has a direct positive and independent effect on the overall QoL. Other nonpharmacological approaches can also be of benefit, either alone or as adjuvant treatments, and are discussed. Conclusion The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients' pain management and subsequent impact on QoL should routinely be assessed and monitored.

Atypical Clinical Presentations of Pediatric Acute Immune-Mediated Polyneuropathy.

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. During the acute phase, the disorder can be life-threatening by involving the respiratory muscles and the autonomic nervous system. Nevertheless, the prognosis is good, and most children achieve full recovery. The aim of this study was to characterize the clinical and electrophysiologic findings in children with Guillain-Barré syndrome referred to a tertiary center in Israel. A retrospective database review from 2009 to 2015 identified 39 children. Data on clinical presentation, respiratory complications, and long-term neurologic outcomes were collected. Atypical clinical findings at admission included asymmetric weakness in 23%, nonascending weakness in 30%, and normal deep tendon reflexes in 28%. Eight children were later diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Electrophysiologic findings, available in 12 patients with Guillain-Barré syndrome, revealed acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 4 (33.5%), AIDP with secondary axonal changes in 3 (25%), and acute motor axonal neuropathy (AMAN) subtype in 4 (33.5%); 8% had no abnormal findings. On follow-up, 71% of the children with Guillain-Barré syndrome fully recovered compared to 14% of the children with CIDP. Corresponding rates of neurologic sequelae were 29% and 86%. Clinicians should be alert to the atypical presenting symptoms of Guillain-Barré syndrome, which occur in a significant proportion of children.

Autoimmune Peripheral Neuropathies and Contribution of Antiganglioside/Sulphatide Autoantibody Testing.

Peripheral immune-mediated polyneuropathies (IMPN) are a diverse group of rare neurological illnesses characterized by nerve damage. Leading morphological features are mostly nerve fibre demyelination or combination of axonal damage and demyelination. There has been remarkable progress in the clinical and electrophysiological categorization of acute (fulminant, life-threatening) and chronic (progressive/remitting-relapsing) immune-mediated neuropathies recently. Besides electrophysiological and morphological makers, autoantibodies against glycolipids or paranodal/nodal molecules have been recommended as candidate markers for IMPN. The progress in testing for autoantibodies (autoAbs) to glycolipids such as gangliosides and sulfatide may have significant implications on the stratification of patients and their treatment response. Thus, this topic was reviewed in a presentation held during the 1st Panhellenic Congress of Autoimmune Diseases, Rheumatology and Clinical Immunology in Portaria, Pelion, Greece. For acute IMPN, often referred to as Guillain-Barré syndrome and its variants, several serological markers including autoAbs to gangliosides and sulphatide have been employed successfully in clinical routine. However, the evolution of serological diagnosis of chronic variants, such as chronic inflammatory demyelinating polyneuropathy or multifocal motor neuropathy, is less satisfactory. Serological diagnostic markers could, therefore, help in the differential diagnosis due to their assumed pathogenic role. Additionally, stratification of patients to improve their response to treatment may be possible. In general, a majority of patients respond well to causal therapy that includes intravenous immunoglobulins and plasmapheresis. As second line therapy options, biologicals (e.g., rituximab) and immunosuppressant or immunomodulatory drugs may be considered when patients do not respond adequately.

Immune-mediated neuropathies

Since the discovery of an acute monophasic paralysis, later coined Guillain-Barré syndrome, almost 100 years ago, and the discovery of chronic, steroid-responsive polyneuropathy 50 years ago, the spectrum of immune-mediated polyneuropathies has broadened, with various subtypes continuing to be identified, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). In general, these disorders are speculated to be caused by autoimmunity to proteins located at the node of Ranvier or components of myelin of peripheral nerves, although disease-associated autoantibodies have not been identified for all disorders. Owing to the numerous subtypes of the immune-mediated neuropathies, making the right diagnosis in daily clinical practice is complicated. Moreover, treating these disorders, particularly their chronic variants, such as CIDP and MMN, poses a challenge. In general, management of these disorders includes immunotherapies, such as corticosteroids, intravenous immunoglobulin or plasma exchange. Improvements in clinical criteria and the emergence of more disease-specific immunotherapies should broaden the therapeutic options for these disabling diseases.

Multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) has specific clinical and electrophysiologic features but can be difficult to diagnose if cases are not typical. Intravenous immunoglobulin (IVIg) remains the core initial and long-term treatment. In this review, recent advances in the diagnosis, monitoring and treatment of MMN are discussed. The pathology of MMN likely depends on immune-mediated attack of the nodes of Ranvier and paranodal regions leading to conduction block. Antiganglioside antibodies are present in over 50% of patients. The sensitivity of antibody detection can be improved by testing for GM1/galactocerebroside (GM1/GalC) complexes. Complement activation plays a key role in the pathophysiology of MMN. Subcutaneous immunoglobulins are an efficacious alternative to IVIg for maintenance therapy in MMN. Complement inhibitor eculizumab may be a potential future treatment, but further studies are necessary. The European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines for the diagnosis of MMN are currently widely used but probably need revision. Nerve ultrasound and plexus/nerve MRI can be helpful in diagnostic dilemmas. Monitoring of disease and response to treatment may improve using disease-specific evaluation scales such as MMN-Rasch-built overall disability scale. Further research into the pathophysiology of MMN is necessary to direct future treatment strategies.

Acute immune-mediated polyneuropathies: The Royal North Shore Hospital experience (P1.155)

Acute immune-mediated polyneuropathies: The Royal North Shore Hospital experience (P1.155)

Comparison of the outcomes of home based and supervised individually designed exercise programme amongst the patients in chronic phase after guillain barre syndrome: study protocol for a randomized control trial

<p class="abstract"><strong>Background:</strong> Guillain barre syndrome (GBS) is an immune mediated polyneuropathy characterized by progressive weakness and variety of symptoms including muscle paralysis, autonomic dysfunction and respiratory involvement that affect one or two persons in 100,000 population. Although immunotherapies including therapeutic plasma exchange (TPE), immunoglobulins (IVIg) and corticosteroids are the available beneficial modes of treatment, the residual symptoms are disabling and long lasting and require long term rehabilitation. Observational studies and RCT on multi-disciplinary care has proven exercises to be an answer to residual long lasting disability. Supervised individually designed exercise prescription after physiotherapy assessment may play a major role in minimizing disability.</p><p class="abstract"><strong>Methods:</strong> The present study is an open-level, parallel, superiority randomized control trial with blinding of outcome assessors to evaluate the results of the individually designed exercise programme over home based exercise programme. 74 adult referred GBS patients will be recruited and randomize in two groups either to receive 12 weeks individually designed exercise programme or home based exercise programme. The primary outcome shall be assessed as functional independence in activities of daily living and secondary outcomes shall be evaluated in terms of muscle strength, fatigue, pain, and quality of life at baseline, six months and twelve months duration.</p><p class="abstract"><strong>Conclusions: </strong>This is the first randomized control trial to compare the effect of supervised individually designed exercise over home based exercise programme on pwGBS.</p><p><strong>Trial registration:</strong> Currently the trial is ethically approved, prospectively registered CTRI/2016/08/007150 and in the process of recruiting its first subjects.</p>

Association of Neutrophil/Lymphocyte Ratio With Intravenous Immunoglobulin Treatment in Children With Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory polyneuropathy of the peripheral nervous system. The authors aimed to investigate whether the neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios are the parameters that associated with the drug treatment or severity of GBS. Twenty-seven children with GBS were retrospectively analyzed from the medical records of patients who attended to the Pediatric Neurology Department of the Gaziantep University Hospital. Biochemical and hematologic parameters were measured. Leukocytes, neutrophils counts and N/L ratio were significantly higher before the intravenous immunoglobulin treatment ( P < .001). However, there were no marked differences in platelet count and P/L ratio. In addition, marked correlation was observed between the N/L ratio after treatment and duration of weakness. The results of the study showed that N/L ratio is significantly higher in GBS patients, and reduces following with intravenous immunoglobulin treatment.

Guillain- Barre Syndrome: A Rare Immune Mediated Polyneuropathy

Guillain- Barre Syndrome: A Rare Immune Mediated Polyneuropathy

An Atypical Case of Guillain-Barré Syndrome Associated With Gastrointestinal Stromal Tumor

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy presenting with classic symptoms of progressive, symmetric muscle weakness and absent or depressed deep tendon reflexes. Molecular mimicry from an immune response to a proceeding infection inciting cross-reaction with peripheral nerves is the proposed etiology of GBS. The most common precipitant of GBS is Campylobacter jejuni infection. Rarely, GBS has been described to occur as a paraneoplastic syndrome with possible malignant triggers including small cell lung cancer and squamous cell carcinoma. We describe a case of GBS associated with gastrointestinal stromal tumor (GIST). To this author's knowledge, there are no other case reports in the literature of GBS associated with GIST. A 65 year-old man with a past medical history of hypertension and type II diabetes mellitus presented with 3 days of paresthesias of the fingers, toes, and mouth, slurred speech, vertigo, and mild hematemesis. His physical exam was significant for bilateral facial nerve palsy, dysarthria, and decreased reflexes in the lower extremities bilaterally. Laboratory results were significant for white blood cell count of 14 and hemoglobin (Hgb) level of 20.2. CT abdomen and pelvis with contrast showed a lobular soft tissue gastric mass 3.4 x 2.5 x 2.9 cm. CT head without contrast showed no acute intracranial process. Lumbar puncture revealed albuminocytologic dissociation. Nerve conduction study and needle electromyography showed demyelinating features. Based on these results, the patient was diagnosed with GBS, specifically the acute inflammatory demyelinating polyneuropathy variant. He was treated with 5 days of intravenous immunoglobulin (IVIG). For the gastric mass, he underwent endoscopic ultrasound-guided biopsy, and the pathology revealed GIST (Figures 1 and 2). Respiratory parameters remained stable, and he had mild improvement with IVIG. Campylobacter jejuni antibody was negative. For the elevated Hgb, the patient was negative for JAK2 V617F and CALR mutation, and erythropoietin was normal, making polycythemia vera unlikely. His Hgb trended down to within normal levels over the next month. The initial elevated Hgb could have been explained by hemoconcentration; however, there are murine models of GIST with KIT activating receptor tyrosine kinase mutations causing hematopoiesis. This case demonstrates a rare case of GBS associated with GIST. The patient is planned for open partial gastrectomy.Figure: Intramural lesion found in the lesser curvature of the stomach. It appears to originate from within the muscularis propria (Layer 4) and invades through the serosa. Fine needle aspiration initial cytology was suggestive of a spindle cell tumor. Sonographic appearance was suggestive of a GIST with concerning features (cystic components, large size, invading through serosa).Figure: EUS-FNA biopsy cytopathology images of GIST. A: Cytopathology conventional smear slide showing clusters of spindle cells typical for GIST (Papanicolaou stain, 200x); B: Cytopathology cell block preparation (H&E stain, 200x); C and D: Immunohistochemical stains performed on cell block section, positive staining of DOG-1 (C) and c-KIT (D) confirms the diagnosis of GIST (200x).

Immune Axonal Polyneuropathy.

Immune axonal polyneuropathy is caused by a diverse group of disorders that share similar presentations and treatment regimens. This article focuses on the clinical findings, evaluation, and management of immune-mediated causes of axonal polyneuropathy, focusing primarily on large fiber sensorimotor polyneuropathy. Specific characteristics of an immune-mediated polyneuropathy have been incorporated in a new diagnostic screening tool that is highly sensitive and can easily be used in the outpatient clinic setting. New insights into autoantibodies may help identify the presence of an underlying autoimmune or paraneoplastic disease as the cause of a polyneuropathy. This article provides readers with further understanding into the autoimmune causes of axonal polyneuropathy and will help the clinician recognize key clinical features that may lead to timely diagnosis and treatment.

Neuropsychiatric debut as a presentation of Guillain-Barré Syndrome: An atypical clinical case and literature review

IntroductionGuillain Barré Syndrome (GBS) is an acute immune-mediated polyneuropathy most frequently presenting two to four weeks after an acute mild-moderately severe infection as progressive muscular weakness of the lower limbs extending proximally with dysreflexia and autonomic dysfunction. While GBS is typically believed to be isolated to the Peripheral Nervous System, Central Nervous System (CNS) and psychiatric manifestations as a sequela of the disease have been described in different imaging and clinical studies. Many variants of presentation of GBS have been recognized, however a case presenting with primarily psychiatric and autonomic dysfunction preceding muscle weakness has not been cited in the literatures to date. Case presentationWe describe a 24-year-old previously healthy male presenting with behavioral symptoms including depression, anxiety, and amnesia, and autonomic dysfunction which preceded muscle weakness by two weeks. CNS imaging and blood work results were unremarkable. GBS was confirmed upon cerebral spinal fluid analysis remarkable for an important cytoalbuminologic dissociation and markedly elevated protein concentration. The patient responded well to five cycles of inpatient plasmapheresis and short-term selective serotonin reuptake inhibitor treatment with complete recovery of both neurological and behavioral symptoms. ConclusionThough GBS is typically considered a peripheral neuropathy, evidence for CNS involvement exists; GBS should be considered within the differential diagnosis, and neurological features should be monitored, in a patient with new onset unclear psychiatric and CNS symptoms.

A Case of Guillain-Barre Syndrome with Significant Lymphocytic Pleocytosis

Guillain-Barre syndrome (GBS) is an immune-mediated polyneuropathy. In the cerebrospinal fluid (CSF) characteristic increased protein without pleocytosis i.e., albuminocytologic dissociation is seen. But cases of GBS with significant CSF lymphocytosis have rarely been reported. Here, we present a 38-year-old man with dysarthria, dysphagia, bilateral facial palsy, and limb weakness with the diagnosis of GBS. Nerve Conduction Study confirmed the diagnosis but interestingly in the CSF study increased protein and lymphocytic predominant pleocytosis were found. Other possible differential diagnoses were ruled out by appropriate paraclinical studies. The patient underwent treatment with intravenous immunoglobulin and showed favorable response.

Mycoplasma pneumoniae triggering the Guillain-Barré syndrome: A case-control study.

Guillain-Barré syndrome (GBS) is an acute postinfectious immune-mediated polyneuropathy. Although preceding respiratory tract infections with Mycoplasma pneumoniae have been reported in some cases, the role of M. pneumoniae in the pathogenesis of GBS remains unclear. We here cultured, for the first time, M. pneumoniae from a GBS patient with antibodies against galactocerebroside (GalC), which cross-reacted with the isolate. This case prompted us to unravel the role of M. pneumoniae in GBS in a case-control study. We included 189 adults and 24 children with GBS and compared them to control cohorts for analysis of serum antibodies against M. pneumoniae (n = 479) and GalC (n = 198). Anti-M. pneumoniae immunoglobulin (Ig) M antibodies were detected in GBS patients and healthy controls in 3% and 0% of adults (p = 0.16) and 21% and 7% of children (p = 0.03), respectively. Anti-GalC antibodies (IgM and/or IgG) were found in 4% of adults and 25% of children with GBS (p = 0.001). Anti-GalC-positive patients showed more-frequent preceding respiratory symptoms, cranial nerve involvement, and a better outcome. Anti-GalC antibodies correlated with anti-M. pneumoniae antibodies (p < 0.001) and cross-reacted with different M. pneumoniae strains. Anti-GalC IgM antibodies were not only found in GBS patients with M. pneumoniae infection, but also in patients without neurological disease (8% vs 9%; p = 0.87), whereas anti-GalC IgG was exclusively found in patients with GBS (9% vs 0%; p = 0.006). M. pneumoniae infection is associated with GBS, more frequently in children than adults, and elicits anti-GalC antibodies, of which specifically anti-GalC IgG may contribute to the pathogenesis of GBS. Ann Neurol 2016;80:566-580.

Immune-mediated neuropathies

The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits.

Guillain-Barre Syndrome Associated with Cyclosporine A

Guillain-Barre syndrome (GBS) is also known as an acute inflammatory demyelinating polyneuropathy (AIDP). It is an immune-mediated polyneuropathy commonly post-infectious in origin that presents with ascending weakness, loss of sensation and deep tendon reflexes resulting from demyelination of peripheral nerve. Drug-induced neuropathy has been describing before and remains a rare clinical entity. Development GBS after an episode of infections such as Campylobacter Jejuni, Epstein Barr Virus, and Mycoplasma pneumonia has been well described. However, GBS associated with Cyclosporine A (CsA) is rarely reported. Here we report a case of GBS developed two weeks after initiation of CsA in a patient with a known case of primary membranous nephropathy and responded well with cessation of the offending drug.

Acute inflammatory demyelinating polyradiculoneuropathy in a newborn infant

Acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barré syndrome, is an immune-mediated polyneuropathy usually triggered by infections or vaccinations. In childhood AIDP is commonly described after the first year of life. Here, we present a case of a newborn infant with AIDP manifestation directly after delivery. A newborn girl with a healthy mother, without known exposure to immunomodulating factors, was admitted to the neuropediatric department due to ascending hypotonia, weakness, pain and areflexia in the lower extremities. The clinical presentation, laboratory and neurophysiological studies supported the diagnosis of AIDP. The infant showed first signs of clinical improvement following administration of intravenous immunoglobulin and her recovery was complete at one year. AIDP should be considered as a differential diagnosis in ascending hypotonia also in the neonatal period.

Electrophysiological pattern of Neuropapathy in Guillain-Barre Syndrome

Guillain Barre Syndrome is an acute immune mediated polyneuropathy. We conducted a prospective study in Neurology Department, Mayo Hospital, Lahore to evaluate different electrophysiological patterns in Guillain Barre Syndrome. A total of 25 cases were registered over the period of one year and nerve conduction and electromyography was done on each patient. The break down of different patterns of neuropathy was 36% demylinated, 12% axonal and 52% of mixed variety having both demylinating and axonal components. From our study we conclude that pattern of neuropathy in GBS is nearly same as reported in most European and local studies except Chinese endemic cases where axonal form is more frequent.

Neuromuscular Ultrasound in the Assessment of Polyneuropathies and Motor Neuron Disease.

Neuromuscular ultrasound is an emerging technology for the evaluation of conditions affecting nerve and muscle, with most of the research focusing on focal neuropathies. Despite this focus, researchers have also investigated the ultrasonographic changes that occur in the nerves and muscles of those with more diffuse polyneuropathies and motor neuron diseases, and this review will detail the findings in these conditions. Specific findings are discussed in this article, but general themes will also be presented and include the following: hereditary polyneuropathies show diffuse nerve enlargement, whereas immune-mediated polyneuropathies show more patchy involvement; nerve enlargement is more profound in demyelinating than axonal polyneuropathies; and muscle changes in motor neuron diseases include heterogeneous increases in echogenicity, atrophy, readily detectable fasciculations, and increased subcutaneous tissue thickness.