Inflammatory Polyneuropathy Research Articles

Epidemiology of neuroimmunological diseases

This review gives an overview of various neuroimmunological diseases in terms of incidence and prevalence rates, age and sex distribution, and the frequency of subtypes, if applicable. The disorders selected for review are inflammatory muscle disorders (polymyositis, dermatomyositis and inclusion body myositis), myasthenia gravis, immune-mediated polyneuropathies (Guillain-Barré syndrome, chronic polyneuritis and vasculitic neuropathies), and multiple sclerosis.

Hypoglossal neuropathy in Lewis-Sumner syndrome masquerading as motor neuron disease

Lewis-Sumner syndrome (LSS) is a peripheral neuropathy characterized by multifocal weakness and wasting and associated sensory impairment1 considered to be a variant of chronic inflammatory polyneuropathy (CIDP). LSS is associated with multifocal persistent conduction block and other signs of demyelination.1,2 We report a patient with probable LSS presenting with tongue hemiatrophy thought to have motor neuron disease. ### Case report. A 56-year-old man with chronic alcoholism presented to the neuromuscular clinic with a 6-year history of progressive painless right arm weakness and right hand paresthesias and a 2-year history of left arm weakness, burning pain, and numbness in the feet, and falls. On evaluation by another neurologist immediately following symptom onset, he was found to have tongue atrophy and fasciculations, right arm weakness and wasting, and decreased sensation in the right hand. MRI of the brain and cervical spinal cord, anti-GM1 antibodies, and genetic testing for Kennedy’s disease were unrevealing. Electrodiagnostic study, limited to sensory and motor nerve conduction study of the right median and ulnar nerves, demonstrated a mildly prolonged median distal motor latency and reduced median sensory nerve conduction velocity across …

Polyradiculoneuritis in Sarajevo During the War

Acute polyradiuloneuritis is acute inflammatory demyelinizing polyneuropathy, with still unknown cause, and which main pathophysiological disorder is degeneration of axons which affects peripheral nerves. Most frequently it occurs as acute, several days or weeks after viral, respiratory or gastrointestinal infections. Survival rate is in the world between 95-98% of cases. The goal of the research is to determine by retrospective study number of cases of acute polyradiculoneuritis during the war in the Sarajevo under the siege and their outcome. In this paper we have analyzed total number of acute polyradiculoneuritis cases within the period since April 1992 until April 1996, when the city of Sarajevo was completely under siege. Diagnostic criteria's besides anamnesis was detailed neurological exam, blood tests, analysis of the cerebrospinal liquor, EMG, ECG and cardiac tests. Within the above mentioned period there was 17 cases of polyradiculoneuritis, 13 male and 4 females, age between 14-65 years. Motor weakness and parestesias was most dominant in clinical image. Number of cases increased during the years and it was greatest during 1995. Previous infections were noted in 6 cases, and 5 of those respiratory, and one case of gastrointestinal. Proteinorahia in liquor was found among 10 cases (4 during first and 6 during the second week of illness). Pathological EMG was found in 8 cases. Milder form of illness had 4 patients, while 13 patients had more severe form. In total 7 patients survived, 2 of them without consequences, 3 with milder and 2 with more severe consequences while in 10 cases there was a lethal outcome.

Diagnostic value of anti-GM1 ganglioside serology and validation of the INCAT-ELISA

The Inflammatory Neuropathy and Treatment (INCAT) group developed a standardized ELISA method for the detection of serum anti-GM1 antibodies. The diagnostic value of anti-GM1 antibodies determined by this method has not yet been established in large groups of patients. We assessed the reproducibility, sources of variation, optimal cut-off values and evaluated the diagnostic relevance of the INCAT-ELISA in various groups of patients and controls ( N = 1232). The coefficient of variance was 11.2% for IgM and 3.8% for IgG. High IgG titers were only found in Guillain–Barré syndrome (GBS) and other inflammatory polyneuropathies. High IgM titers were associated with GBS and multifocal motor neuropathy. Low IgM titers had no additional diagnostic value. The INCAT-ELISA is a reliable test with additional diagnostic value in specific clinical situations.

Anti-phospholipid antibodies in serum from patients with Guillain-Barré syndrome

The Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy related to autoimmunity. However, no conclusive etiological concept has yet been found. We examined the variation in autoantibodies to lipids in serum of GBS patients in response to the course of the disease but investigated titer modifications during treatment with gamma-globulin. Prospective clinical study in a 14-bed general ICU. Nine patients with GBS and nine controls were included in the study. Four blood samples were obtained before and after treatment. Serum samples, diluted 1:60, were tested by enzyme-linked immunosorbent assay for IgM, IgA, and IgG antibodies to phosphatidylcholine, phosphatidylinositol, cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, sphingomyelin, and gangliosides. Anti-phospholipid antibodies of the IgM, IgA, and IgG families were detected in all GBS patients but in none of the controls. Phosphatidylinositol, cardiolipin, phosphatidylcholine, and phosphatidic acid were the main antigens. All patients developed anti-phosphatidylinositol antibodies of the IgM family and anti-cardiolipin antibodies of the IgA and IgG families. A decrease in the level of anti-phospholipid autoantibodies was observed after 1 day of treatment with gamma-globulin. Two days after ending gamma-globulin administration the IgG antibodies increased again. Our findings suggest that in GBS there is an extensive immune reaction, which is altered after gamma-globulin treatment. Anti-cardiolipin and anti-phosphatidylinositol antibodies could be useful markers for the response to treatment.

Successful hematopoietic stem‐cell transplantation in multicentric Castleman disease complicated by POEMS syndrome

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.

Acute inflammatory sensorimotor polyradiculoneuropathy associated with immune thrombocytopenic purpura

Although acute inflammatory polyneuropathy (AIP) and immune thrombocytopenic purpura (ITP) are both believed to be immune-mediated disorders, only a few cases have been reported in which these two diseases co-existed. We describe a case of a 67-year-old patient who developed quadriparesis, ophthalmoplegia and severe sensory impairment along with thrombocytopenia. Detailed examinations, including the measurement of anti-ganglioside antibodies and anti-glycoprotein-IIb-IIIa-IgG-producing B-cells, revealed that he developed AIP and ITP. By reviewing past similar reports, we noticed that AIP associated with ITP tends to manifest severe sensory impairment and is often preceded by upper respiratory tract infection, but not by gastrointestinal infection.

Chronic inflammatory polyneuropathy as an early symptom of metachromatic leukodystrophy: two case reports

Metachromatic leukodystrophy (MLD) is an autosomal recessively transmitted progessive white matter disease. Four types with different clinical onset and progression are known. MLD is diagnosed by an absent activity of the enzyme arylsulfatase A, demyelinisation is detected by cerebral MRI.

129th ENMC International Workshop: Clinical Trials for Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy, 27th October 2004, Schiphol airport, The Netherlands

There is uncertainty about the best immunosuppressive treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and consequently a wide variation in practice. CIDP affects between 2 and 8 per 100,000 and MMN has a prevalence about 10 times lower. Both conditions are economically important because intravenous immunoglobulin (IVIg) is often used in their treatment and is very expensive especially because of the need for repeated courses. Multicentre trials are necessary to provide sufficient participants for adequately powered trials and need to be conducted at a multinational level. The evidence for treatment has been systematically reviewed in Cochrane reviews [1,2] and a previous ENMC workshop had already considered MMN [3]. In CIDP steroids, IVIg or plasma exchange (PE) and in MMN IVIg provide short-term benefit but the value of immunosuppressant treatment has not been adequately evaluated. Encouragingly there are four ongoing trials in CIDP and one in MMN. A Bayer trial compares IVIg with placebo over a longer period than has been tested before (M MaasEnriquez, personal communication). A Biogen-Idec trial tests whether interferon-beta 1a will reduce the requirement for IVIg [4]. A Dutch trial aims to find out whether pulsed high dose dexamethasone induces remissions more often and more rapidly and is more effective than standard prednisolone treatment (I van Schaik personal communication). An Italian trial aims to compare IVIg and high dose

Characterization of genetically defined types of Charcot-Marie-Tooth neuropathies by using magnetic resonance neurography

Charcot-Marie-Tooth (CMT) disease is a collection of related genetic disorders affecting peripheral nerves with an incidence of one in every 2500 individuals. A diagnosis of CMT disease has classically relied on a medical history, examination, and measurement of nerve conduction velocities. Advancements in genetic testing and magnetic resonance (MR) imaging techniques may provide clinicians with a more precise diagnostic armamentarium. The authors investigated MR neurography as a possible method to characterize CMT subtypes. The authors performed MR neurography to evaluate sciatic nerves in the mid-thigh area of seven patients with genetically defined subtypes of CMT, one patient with chronic inflammatory demylinating polyneuropathy, and one patient without neuropathy. The authors correlate their findings with normal nerve conduction velocities (NCVs) and present their results as a descriptive case series. Although MR neurography could not be used to distinguish subtypes of CMT disease on nerve area or fascicle number, it appears to characterize phenotypic features and disease progression noninvasively in patients with some subtypes. In conjunction with NCV measurements, MR neurography may be useful in the diagnosis of CMT neuropathies and in monitoring disease progression.

Aggravation aiguë régressive d’une maladie de Charcot-Marie-Tooth de type 1B : la Protéine P0 peut-elle agir comme un auto-antigène ?

The natural history of Charcot-Marie-Tooth neuropathy is marked by accentuated motor and sensitive deficits suggestive of acute polyradiculoneuritis or, more generally, chronic inflammatory demyelinizing polyneuropathy. A 41-year-old woman, with Charcot-Marie-Tooth (CMT) 1B neuropathy associated with a P0 gene mutation, developed several episodes of ataxia which resolved after intravenous administration of IgG or corticosteroids. The sudden increase of a motor or sensitive deficit in this patient with CMT type I led to two hypotheses: chance association between an inherited and an inflammatory neuropathy, or a dysimmune inflammatory reaction, the mutated protein acting like an autoantigen. These two hypotheses are discussed.

IRM du plexus brachial

Magnetic resonance imaging is the method of choice for the evaluation of brachial plexopathy. Knowledge of the anatomy and normal imaging appearance is required. High-resolution imaging technique is necessary with the use of adequate coils. Evaluation of the brachial plexus requires T1 weighted sequences in three plans, T2 weighted sequences with fat suppression and if necessary the study is completed with gadolinium injection sequences with fat suppression. A CISS sequence is used if a nerve root avulsion is suspected. The spatial resolution must be optimized with the use of adapted parameters. We illustrate a variety of pathologies that can involve the brachial plexus. The pathology includes trauma, primary (neurogenic tumors, lymphomatosis) or secondary tumors, radiation plexopathy or inflammatory polyneuropathy.

Immunologic profile in chronic inflammatory polyneuropathies associated or not associated with MGUS

Chronic inflammatory polyneuropathies (CIP) may be associated with monoclonal gammopathies (MGUS) directed or not against neuropathy‐related antigens. We analysed peripheral T and B cell subsets and cytokine network in 13 patients with CIP without MGUS (CIP), 10 with CIP with MGUS anti‐MAG (CIP‐MAG) and 5 with CIP with MGUS without anti‐MAG activity (CIP‐MGUS). We evaluated, by flow cytometry, CD3+, CD3 + DRII+, CD4+, CD8+, CD16+ and CD19+ cells subset distribution, and intracellular IL2, INFg, IL1, IL6, IL10 and TNFa production by CD4+, CD8+ and CD14+ cells. Results were compared with age‐matched healthy controls (HC); statistical analysis was performed. Compared to HC, CIP patients had a significant decrease of CD3+ and B cells, CIP‐MAG patients had an increase of CD3+ and NK and a decrease of CD3 + DRII+ and B cells. Comparing the different subgroups, we found a decrease of CD3 + DRII+ and B cells in CIP‐MAG versus CIP, and an increase of CD4+ in CIP‐MGUS versus CIP. Compared to HC, CIP showed an increase of INFg in CD4+ and of IL6 in CD14+. CIP‐MAG showed an increase of IL10 in CD4+, IL1 and IL10 in CD8+, and IL1 in CD14+, versus HC and other subgroups. Our results suggest that in CIP‐MAG patients it is possible to identify a distinct immunological profle.

Chronic relapsing polyneuropathy associated with hepatitis B virus infection

We report the case of a 50‐year‐old woman affected by a chronic latent Hepatitis B (H.B.V.) virus infection since the age of 35, who complained of several relapses of sub‐acute sensorimotor inflammatory polyneuropathy with albumino‐cytological dissociation, successfully treated with IVIg pulse therapy during acute phase and with chronic prednisone therapy. An exacerbation of H.B.V. infection, likely induced by corticosteroid administration, associated with marked increase in serum of hepatic enzymes and high H.B.V. DNA levels in blood, coincided with a severe worsening of the neuropathy. Laboratory investigations revealed, among others, elements of renal involvement (hypoalbuminemia, proteinuria). Immunofixation electrophoresis revealed an IgM (k) monoclonal gammopathy, antibody testing high level of IgM to GD1a (1/81920). Lamivudina, rituximab and IVIg were administered: renal and liver indexes re‐entered within the ranges, sensorimotor deficits had slow and incomplete remission. In this case, polyneuropathy could be an expression of systemic H.B.V. illness mediated by a specific immunogenic attack in the phase of chronic latent infection, mediated by immune‐complexes precipitation in the reactivation phase, as the renal involvement seems to suggest. The pathological mechanism is under discussion.

A point of view: The need to identify an antigen in psyconeuroimmunological disorders.

Several lines of evidence support a mutual relationship between the nervous system and the immune system. Therefore, it is not surprising that some neuropsychiatric disorders are also characterized by immune abnormalities. In patients with phobic disorders and in patients with migraine without aura some common immune abnormalities have been detected and, in particular, natural immunity deficits, exaggerated release of proinflammatory cytokines and circulating bacterial endotoxins have been found. In other neurological disease, some etiologic factors have been detected as in the case of Guillain-Barrè syndrome in which molecular mimicry between Campylobacter jejuni endotoxin and GM1 ganglioside may cause an acute inflammatory polyneuropathy. On the other hand, attempts to identify an antigen have been made in patients with Alzheimer's disease and schizophrenia. Finally, the chronic fatigue syndrome, an old illness in search for an antigen, risk factors and precipitating agents have been described but evidence for a specific antigen is still lacking.

Acute Management of Guillain-Barré Syndrome

Guillain-Barré Syndrome (GBS) is an acute inflammatory polyneuropathy. Typical presentation is one of ascending tetraparesis with aref lexia. Variant forms of GBS include ataxia and ophthalmoplegia with aref lexia; patients with preserved ref lexes may mislead the unwary. Diagnostic dilemmas may be solved with neurophysiology and lumbar puncture. Emergency management requires assessment of airway, breathing and circulation. Regular monitoring of respiratory, and bulbar function is essential and any deterioration in neurological function should prompt treatment. Treatment with intravenous immunoglubulin shortens the length of illness.

Guillain‐Barré syndrome

Acute Inflammatory polyneuropathies are an important group of neuromuscular disorders and are referred to collectively as Guillain-Barre syndrome (GBS). Our knowledge regarding pathogenesis, diagnosis and management continues to expand, resulting in improved opportunities for identification and treatment. These autoimmune processes cause neuropathy by affecting various structures (myelin or axons), at different locations (nerve root, nerve cell bodies or peripheral nerve) with a variety of patterns. Most clinical neurologists will be involved in the management of patients with these disorders, and there are now a variety of reasonable therapies available for acquired demyelinating neuropathies. In this report, we review the distinctive clinical, laboratory and electro-diagnostic features that aid in their diagnosis, with emphasis on clinical characteristics that are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies, and helpful in determining long-term prognosis.

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 82

A 69‐year‐old right‐handed man was recently referred to our institution with a two‐month history of diplopia and ptosis in his left eye: the ocular symptoms typically fluctuates during the day, being least severe in the morning and worsening as the day progress or while reading or driving. Neostigmine injection produced a clear improvement of weakness. The serum concentration of anti‐AChR antibody was elevated > 8.4 nmol/L (NV < 0.4); a chest CT scan was unremarkable with no evidence of mediastinal mass. The clinical picture and laboratory tests support the diagnosis of ocular myasthenia. His past medical history was insignificant until the age of 59. At that time, he complained with a diffuse, slightly asymmetrical muscle weakness both in the upper and lower limbs and sensory symptoms of glove and stocking distribution (numbness). A progressive course over months was seen with hand and anterior leg muscles hypertrophy becoming evident. Strength was decreased distally greater than proximally in the upper and lower extremities. Deep tendon reflexes were absent. The cerebrospinal fluid demonstrated a protein level of 72 mg/dl (NV < 45 mg/dl). Nerve conduction study showed a multifocal sensory‐motor polyneuropathy with both conduction block/temporal dispersion of the C‐MAP and slowing of the velocity. A diagnosis of chronic inflammatory polyneuropathy (CIDP) was considered and the patient was treated with steroids, plasmapheresis and azathiaprine: after a slight improvement, the condition has been stabilized. Both MG and CIDP have been individually associated with disorders of presumed autoimmune pathogenesis. Their concurrence is rarely found (less than 10 cases to the best of our knowledge): although the existence of this syndrome can be strongly supported by the clinical, electrophysiological and laboratory data, a common basic abnormality of immune regulation is still unknown.

Matrix metalloproteinases-9 and -2 in secondary vasculitic neuropathies.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteinases that play an important role in inflammation and tissue degradation. MMP-9 and MMP-2 are gelatinases that have been implicated in the degradation of the blood-brain or blood-nerve barrier. We present an immunohistochemical study on 11 nerve biopsy samples of inflammatory and non-inflammatory polyneuropathies. Perineurium and endothelium were positive for MMP-2 in all tissue sections. In addition, there was a specific up-regulation of MMP-2 in stromal cells of chronic inflammatory demyelinating polyneuropathy (CIDP) and even more in vasculitic neuropathies. MMP-9-positive cells were detected in vessel walls, infiltrates, epineurium and endoneurium of vasculitic neuropathies. In CIDP, MMP-9-positive cells were prominent in vessel walls. Only a few MMP-9-positive cells were detected in noninflammatory controls in blood vessels and adhering to vessel walls. Double staining indicated that the infiltrating cells were T cells and macrophages. Our findings suggest that MMP-9 plays an important role in inflammatory peripheral neuropathy probably as means for inflammatory cell invasion.

Multiple MAG peptides are recognized by circulating T and B lymphocytes in polyneuropathy and multiple sclerosis.

Abnormal immune responses to myelin associated glycoprotein (MAG), a component of myelin of the central and peripheral nervous system, have been suggested to play a role in the pathogenesis of multiple sclerosis (MS) and certain types of inflammatory polyneuropathy. To identify possible immunodominant MAG peptides in neuroinflammation, we examined T and B cell responses to five selected synthetic MAG peptides and myelin proteins in 21 patients with non-inflammatory polyneuropathy, 26 patients with MS, 10 optic neuritis patients and 17 healthy subjects. Enzyme-linked immunosorbent spot-forming cell assays were adopted, allowing the detection and enumeration of individual antigen responsive T and B cells in body fluids. Patients with polyneuropathy as well as those with MS had elevated levels of T and B cells recognizing MAG and its peptides. Any of the five MAG peptides under study functioned as immunodominant T and/or B cell epitope in individual subjects. None of the MAG peptides elicited a specific disease-associated T or B cell response. The enhanced T and B cell response to myelin components like MAG may play some role in initiation and/or progression of these diseases, but they could also represent secondary responses associated with myelin damage and indicate tolerization rather than autoaggressive immunity.