Chronic Inflammatory Demyelinating Neuropathy Research Articles

Paraproteinemic neuropathies.

The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with peripheral neuropathy. Our role, as physicians, is to determine whether the neuropathy is directly related to the gammopathy or whether the co-occurrence of these two disorders is purely coincidental. The evaluating physician needs to be familiar with the different types of neuropathies associated with monoclonal gammopathies, their clinical and electrodiagnostic characteristics, and their appropriate diagnostic evaluation and management. Testing for monoclonal protein disorders includes serum protein electrophoresis (SPEP) and immunofixation of blood, and in some cases of urine, as well as measurement of free light chains and quantitative immunoglobulins. Specific antibody testing is directed by paraprotein type and neuropathy phenotype. Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis. When a lambda monoclonal protein is identified together with a clinical phenotype of chronic inflammatory demyelinating neuropathy (CIDP), a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome should be considered. Patients with IgM paraprotein associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti myelin associated glycoprotein (MAG) antibody or CANOMAD syndrome. In many cases, a monoclonal gammopathy of uncertain significance (MGUS) is incidental and unrelated to the neuropathy. Collaboration with oncology is critical in evaluating patients with monoclonal proteins to assess for underlying plasma cell neoplasms or B cell lymphomas.

Database Evaluation for Muscle and Nerve Diseases - DEMAND: An academic neuromuscular coding system

Background: A database which documents the diagnosis of neuromuscular patients is useful for determining the types of patients referred to academic centers and for identifying participants for clinical trials and other studies. The ICD-9 or ICD-10 numeric systems are insufficiently detailed for this purpose. Objective: To develop a database for neuromuscular diagnoses Methods: We developed a detailed diagnostic coding system for neuromuscular diseases called DEMAND: Database Evaluation for Muscle and Nerve Diseases that has been adopted by neuromuscular clinics at University of Texas Health Science Center San Antonio (UTHSCSA), Ohio State University (OSU), University of Kansas Medical Center (KUMC), and University of Texas Southwestern (UTSW). At the initial visit, patients are assigned a diagnostic code which can be revised later if appropriate. Fields include patient’s name, date of birth, and diagnostic code. The neuromuscular database consisted of 457 codes. Each code has a prefix (MUS or PNS) followed by a three-digit number. Depending on whether muscle or nerve is primarily involved, there are eight broad groups: motor neuron disease (MUS codes 100-139); neuromuscular junction disorders (MUS 200-217); acquired and hereditary myopathies (MUS 300-600s); acquired and hereditary polyneuropathies (PNS 100-400); mononeuropathies (PNS 500s); plexopathies (PNS 600s); radiculopathies (PNS 700s); and mononeuritis multiplex (PNS 800s). Results: During a period of 10 years, 17,163 of patients were entered (1,752 at UTHSCSA, 1,840 at OSU, 3,699 at KUMC, 9,872 at UTSW). The number of patients in several broad categories are: 3,080 motor neuron disease; 1,575 neuromuscular junction disease; 1,851 muscular dystrophies; 633 inflammatory myopathies; 1,090 hereditary neuropathies; 1,001 immune-mediated polyneuropathies; 620 metabolic/toxic polyneuropathies; 535 mononeuropathies; 296 plexopathies; and 769 radiculopathies. Conclusion: A detailed diagnostic neuromuscular database can be utilized at multiple academic centers. The database should be simple without too many fields to complete, to ensure compliance during busy clinic operations. This database has been very useful in identifying groups of patients for retrospective, observational studies and for prospective treatment studies including trials for Amyotrophic Lateral Sclerosis (ALS), Muscular Dystrophies (MD), Myasthenia Gravis (MG), and retrospective studies of Primary Lateral Sclerosis (PLS), chronic inflammatory demyelinating neuropathy (CIDP), etc.

BI23 Erythrodermic eczematous reactions to immunoglobulins

Abstract Intravenous immunoglobulins (IVIg) have been used in clinical practice for more than 50 years. They are used for dermatological indications such as dermatomyositis, pemphigus and Kawasaki disease. Although this is regarded as a safe treatment modality, it can produce adverse reactions in the skin. We report two patients with IVIg-induced skin changes. A 71-year-old man with no preceding skin disease was under neurology care for the treatment of chronic inflammatory demyelinating neuropathy (CIDP) with IVIg. He presented with an erythrodermic eczematous rash and was symptomatic with pain and pruritus. The rash started on the hands and had spread to the rest of the body 3 days after completion of his third course of IVIg. He was treated with topical clobetasol propionate. His skin settled over the course of a few weeks. The patient was keen to resume IVIg for CIDP; unfortunately, he developed a more severe and rapid reaction on retrial and IVIg had to be stopped. An 82-year-old man was given IVIg for CIDP. He denied any previous skin conditions or atopy. He received a 5-day course of IVIg followed by intravenous methylprednisolone 1 g once daily for 6 days. Four weeks later, he developed pompholyx on the palms and thereafter a widespread eczematous rash over the arms, abdomen, back and face. He was treated with topical clobetasol propionate to the trunk and limbs and clobetasone butyrate to the face. His rash and symptoms settled with topical treatment. Eczematous immunoglobulin reactions are often under-recognized. Reactions preferentially affect middle-aged men and those being treated for neurological disease. The clinical presentation is peculiar and distinctive, almost always involving the palmoplantar aspects with a dyshydrotic element. The reaction pattern starts within a few days to weeks of exposure to immunoglobulins and can become erythrodermic. Histology shows a spongiotic dermatitis and is not diagnostic. Immunoglobulin-associated eczema can persist even after the discontinuation of immunoglobulins. Recommended treatment depends on severity. If mild, continuing immunoglobulins with topical steroids should be considered. If the reaction persists or worsens, up to two switches of the immunoglobulin brand can be considered. In severe or persistent cases, methotrexate may be beneficial. The mechanism of an IVIg-induced skin reaction is not fully understood. The diagnosis of eczematous IVIg reaction is clinical, with a high index of suspicion required. The care of these patients requires collaboration between dermatologists and the physician prescribing the immunoglobulin, who may be unfamiliar with this adverse event.

Disease activity in chronic inflammatory demyelinating polyneuropathy: A comparative study of clinical and skin biopsy markers.

Epidermal nerve fiber involvement in chronic inflammatory demyelinating neuropathy (CIDP) has been reported in a limited number of patients. We quantified small-fiber involvement in a mixed cohort of patients with typical CIDP and CIDP variants to evaluate relationships with clinical outcome measures at different disease stages. Intraepidermal nerve fiber densities (IENFDs) were evaluated by skin punch biopsies of 23 patients with CIDP and 13 healthy controls at the forearm, thigh, and distal leg. Skin sections were optimally interpreted in all three regions in 16 CIDP patients and 10 age- and sex-matched healthy controls. Statistical analysis was performed in these subjects. The IENFDs in forearm, thigh, and distal leg were similar among seven typical CIDP and nine CIDP variants. IENFDs in those regions were significantly reduced in CIDP compared with healthy controls, with a moderate negative correlation with scores on the International Neuropathy Cause and Treatment (INCAT) Upper Limb Functional Disability Scale. The reduction in IENFD compared with controls was more remarkable in the distal leg. In clinically unstable CIDP patients, the IENFDs of distal leg and forearm were significantly reduced compared with stable CIDP patients and controls. Stable CIDP patients had significantly reduced IENFDs in distal leg and forearm compared with controls. In this exploratory study, we confirm that small fibers are also affected in CIDP. Larger studies are needed to explore longitudinal changes of IENFD in CIDP and its relation to disease stage.

S2025 Eosinophilic Enterocolitis Improved After Breast Reduction

Introduction: Hypereosinophilic Syndrome (HES) is a group of disorders characterized by an accumulation of eosinophils within peripheral tissues or blood, with manifestations dependent on organ involvement. Eosinophilic gastrointestinal disorders (EGIDs) is one manifestation. In our case, it is believed that antigenic leakage from ruptured silicone breast implants was the proximate cause, as the patient had complete resolution of symptoms and normalization of labs after implant removal. Case Description/Methods: Our patient is a 59-year-old female with a history of asthma, who presents with new-onset sharp epigastric pain worsened with oral intake and associated with diarrhea. Recent evaluation at another hospital for leg weakness revealed peripheral eosinophilia and electromyography showed chronic inflammatory demyelinating neuropathy. After a full diagnostic evaluation for HES, she was diagnosed with idiopathic HES and treated with low dose steroids, IVIG and plasmapheresis without clinical improvement. At our hospital, labs revealed a white count of 35,000/μL, eosinophil count of 21,960/mm3 and IgE of 1299 IU/mL (Table). A CT scan revealed descending colon wall thickening, and intracapsular rupture of the right breast implant. Enteroscopy demonstrated erosions and ulcerations of the duodenum and jejunum. Colonoscopy showed areas of focal ulcerations with surrounding inflammation separated by normal mucosa and histology showed eosinophilic infiltration throughout. Video capsule endoscopy demonstrated diffuse inflammation and ulceration of the entire small bowel. She was empirically treated for strongyloides before starting high dose prednisone therapy. A month later, her breast implants were removed elsewhere. After a short interval, she was successfully tapered off steroids and achieved resolution of both her GI symptoms and lower extremity weakness, as well as normalization of lab work (Figure). Discussion: EGIDs are believed to be multifactorial with an emphasis on immunologic factors. Eosinophilic infiltration seen on biopsies and exclusion of secondary causes is required. Treatment is aimed at symptomatic improvement and removal of offending agent, as seen with our patient who experienced complete clinical resolution after removal of her silicone breast implants. Our case highlights a rare case of eosinophilic enterocolitis associated with a ruptured breast implant in an otherwise healthy patient and emphasizes the importance of remaining vigilant of all external factors that may be contributing to the disease process.Figure 1.: A, B: Small intestine duodenum & Jejunum. C, D: Colonic areas of inflammation. Table 1. - Initial labs versus labs post implant removal Units Reference Labs Initial Labs Labs post implant removal White Blood Count μL 4.0 - 10.5 35 x 103 7.1 Hemoglobin g/dL 11.2 - 15.7 9.6 11.2 Platelets μL 150-400 508 x 103 369 Eosinophil # μL 0.04 - 0.36 21,960 2.5 Eosinophils % 0.7-5.8 61 35 IgE IU/mL < 100 1299

Role of the peripheral nervous system for an appropriate postural preparation during gait initiation in patients with a chronic inflammatory demyelinating polyneuropathy: A pilot study.

Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). During attentional tasks, these APAs can be modulated, producing multiple APAs. However, the role of the peripheral nervous system in the regulation of these APAs is unknown. The objective of our study was to investigate whether APAs are also regulated by peripheral nervous afferents. We assessed 21 patients suffering from chronic inflammatory demyelinating neuropathy and 20 healthy controls. Participants initiated gait with the right or left leg either freely (in the standard condition) or according to a visual trigger (i.e., the select condition). Kinetic and kinematic parameters of APAs and step initiation were recorded. The select condition was related to a higher rate of multiple APAs compared to the standard condition, and was more attention-consuming in both groups. The group with a neuropathy showed longer APAs than the control group, associated with a longer time to recover from multiple APAs. Consequently, the step execution time was delayed in patients with a peripheral neuropathy. The impairment of the peripheral nervous system is therefore responsible for an alteration of the mechanisms underlying the recovery from multiple APAs during gait initiation. Our results are in favor of a role of proprioceptive afferents in the early peripheral regulation of motor errors. Further study on gait initiation in peripheral nervous disease could be helpful to better explore sensory-motor coupling in tasks requiring balance control.

Treatment of acute and chronic inflammatory neuropathies

Guillain-Barré-Syndrome can be treated with intravenous immunoglobulins (IVIG) or with plasma exchange. Superiority of one treatment modality over the other has not been shown. How to manage patients with a disease refractory to these two treatment options is still unclear. Complement inhibitors are in clinical trials. Supportive and even intensive care treatment is needed for many patients, as well as rehabilitation treatment. The chronic inflammatory demyelinating neuropathy, CIDP, can be treated either with IVIG or with corticosteroids.

An ambispective cohort study of chronic inflammatory demyelinating neuropathy, and its variants

BACKGROUND: The clinical presentation, findings, and outcome may vary between typical chronic inflammatory demyelinating polyradiculopathy (CIDP) and its variants. Aims and Objective: To compare clinical profile and outcome of typical CIDP and its variants.

Unraveling the Mystery of Polyvalent Immunoglobulins in Belgium: Do We Have an Indication?

Introduction: Worldwide, polyvalent immunoglobulin (Ig) use is rising. Together with the limited supply, this puts pressure on Ig availability. A clear overview on a country’s usage pattern helps in forecasting future needs. This research aims to provide an overview of Ig use in Belgium on the different indications, including an estimation of off-label use. Methods: Multiple data sources were used. Existing claims data were explored for reimbursed Ig use between 2010 and 2018. General 2018 sales data from the firms were compared to the reimbursed use to serve as a proxy for off-label use. Indication-specific information was retrieved via a proxy: diagnostic codes available during day-care and inpatient hospitalization. Results: In 2018, 7,556 patients had reimbursed Ig. The most prevalent indication, both in terms of patient numbers and volume, was primary immunodeficiency (PID). In Belgian hospitals, the currently reimbursed indications represented 84.4% of patients (PID [≈35%], secondary immunodeficiency [SID] [≈21%], primary immune thrombocytopenia [≈10%], chronic inflammatory demyelinating neuropathy [CIDP] [≈8%], Guillain-Barre syndrome [≈6%], Kawasaki [≈2%], streptococcal toxic shock [≈2%] and multiple motor neuropathy [≈1%]), and 82.4% of Ig use (predominantly PID [≈33%] and CIDP [≈21%]). Although no direct data on off-label use were available, crude estimates derived from indirect sources showed a proportion of around 15.4%. Conclusion: Our research offers the first comprehensive overview on Ig use in Belgium, including a detailed description of reimbursed use, as well as approximations to off-label use. In view of increasing pressure on Ig availability, better understanding Ig needs and trends, would benefit from an effective indication-specific national registry system (ideally covering both reimbursed and nonreimbursed use).

The complex association between pain and neuropathy.

Several studies of patients with polyneuropathy failed to show differences between patients with and without pain. In the current study, we aimed to explore the association between neuropathic symptoms, mainly pain, and polyneuropathy characteristics. A prospective cross-sectional study recruiting 151 patients with non-diabetic polyneuropathy was performed between November 2016 and May 2017. A total of 38 patients with chronic inflammatory demyelinating neuropathy were excluded. Patients underwent clinical, electrophysiological and functional assessments of their polyneuropathy. Polyneuropathy characteristics were compared depending on the presence and severity of neuropathic symptoms. The presence and the severity of weakness were associated with a more severe neuropathy as measured by clinical, electrophysiological and functional assessments, while the presence of pain was associated with higher sural amplitudes, and the severity of pain showed a curvilinear association with neuropathy severity. Our study shows a novel finding of a curvilinear association between pain and polyneuropathy severity.

Diabetic Cidp-Like Neuropathy in a Pazient With Becker’s Myotonia

Becker’s disease (BM) is an autosomal recessive congenital myotonia, characterized by impaired muscle relaxation after voluntary contraction and variable degrees of muscle weakness. BM is caused by mutations in CLCN1 gene on chromosome 7q35 encoding the major skeletal muscle chloride channel CLC-1. Although neuropathy has been associated with myotonic dystrophy, to date no case of neuropathy during the course of BM has been reported. Herein we describe the case of a patient with BM and diabetes who progressive gait disturbance, distal paresthesias, muscle weakness. Neurophysiological assessment and diagnostic lumbar puncture revealed the presence of a chronic inflammatory demyelinating neuropathy. The case here presented developed a diabetic chronic demyelinating inflammatory neuropathy resembling CIDP during the course of BM. The most consistent hypothesis explaining such an unusual association is that the inflammatory neuropathy is related to the concomitant occurrence of diabetes.

Anesthesitic management for insulinoma resection in a patient having chronic inflammatory demyelinating neuropathy

Chronic Inflammatory Demyelinating Polyneuropathy associated with hypoglycemia 2 to insulinoma is unusual, and to our knowledge, very few patients have been reported in literature. Despite varying presentations in these patients, the clinical characteristics are usually the same. The syndrome usually occurs after several episodes of protracted hypoglycemia. The neuropathy is nearly always symmetrical. We report anesthetic management for a young female patient presenting with CIDP &amp; repeated hypoglycemic episodes during a 2-year period scheduled for insulinoma enucleation.

IVIG efficacy in CIDP patients is not associated with terminal complement inhibition

Patients with acute and chronic inflammatory demyelinating neuropathies exhibit elevated serum and cerebrospinal fluid (CSF) levels of terminal complement activation products and therapeutic inhibition of complement activation is currently tested for its safety and efficacy in patients with Guillain-Barré syndrome (GBS). Here, we determined serum levels of the complement activation products C3a, C5a and the soluble terminal complement complex (sTCC) in 39 individuals with chronic inflammatory demyelinating polyneuropathy (CIDP) who participated in one of the largest ever conducted clinical trial in patients with CIDP (ICE trial) and received Intravenous Immunoglobulin (IVIG) or placebo (albumin) in 3 week intervals for up to 24 weeks. In placebo-treated patients with spontaneous disease remission, serum sTCC levels moderately decreased over time. Levels of complement activation products were, however, not modulated by IVIG and remained unchanged in patients with a beneficial response to IVIG therapy as compared to those with steady or worsened disease. These results suggest that the therapeutic efficacy of IVIG in CIDP is based on immunomodulatory mechanisms different from complement inhibition. Terminal complement activation merits further investigation as a surrogate marker for disease progression and therapeutic target in patients with CIDP.

CK prognostic factor in fast/slow progressive Amyotrophic Lateral Sclerosis (ALS)

To measure serum creatine kinase (CK) and myoglobin in ALS and Chronic Inflammatory Demyelinating Neuropathy (CIDP) patients with secondary axonal damage to investigate mechanisms of muscular damage and to assess whether CK in ALS is correlated with clinical features and disease progression. CK and myoglobin were quantified in 116 ALS and 46 CIDP. Patients with ALS were followed for 20 months, subdivided in fast or slow disease progressors according to mean monthly reduction of functional scale (ALSFRS score), whereas CK was measured at different times. Relationship with onset site, proximal and distal nerve compound action potential (cMAP) was analyzed. At baseline CK was raised in ALS patients with spinal compared to bulbar onset. CK in CIDP patients was normal. Myoglobin was normal in both diseases. Slow progressive patients showed higher CK than fast progressive (p

Diaphragmatic dysfunction as the presenting symptom in neuromuscular disorders: A retrospective longitudinal study of etiology and outcome in 30 German patients

Diaphragmatic dysfunction is well-known in advanced stages of neuromuscular disorders. However, data on its presence as the presenting symptom in neuromuscular disorders is scarce. The goal of this retrospective longitudinal study was to evaluate the etiology and clinical outcome in patients, in whom uni- or bilateral diaphragmatic dysfunction was primarily diagnosed, before a specific neuromuscular disease was found. Patients with critical illness neuropathy/myopathy were excluded from this study. Analysis of the medical records of two tertiary referral centers for patients with neuromuscular diseases identified 30 corresponding patients with diaphragmatic dysfunction (17 unilateral; 13 bilateral). Phrenic neuropathy was found in 28 patients, one patient suffered from myasthenia gravis and another from Pompe disease. In 71% of patients with phrenic neuropathy a definite diagnosis could be established (iatrogenic lesion; amyotrophic lateral sclerosis; neuralgic amyotrophy; neuroborreliosis; multifocal motor neuropathy; chronic inflammatory demyelinating neuropathy; post-polio syndrome; spondylosis affecting the nerve root C4/5; and diabetes mellitus). When excluding all 5 patients with amyotrophic lateral sclerosis and further 3 with no follow-up data from outcome analysis, full or partial recovery was seen in 23% or 50% of patients, respectively. Early respiratory and electrophysiological work-ups are mandatory to ascertain the diagnosis and etiology of diaphragmatic dysfunction and to initiate therapy and counseling.

Peripheral neuropathy and the role of nerve biopsy: A revisit.

Nerve biopsy has been widely used to investigate patients with peripheral neuropathy and in many centers, it is still a part of the diagnostic armamentarium. In this study, the histopathological spectrum of the nerve biopsies received is being revisited to analyze the various clinical and pathologic features and also to assess their relevance. Retrospective analysis of the data retrieved was done for 74 cases of nerve biopsies. On the basis of the data and histopathological features, broad diagnoses were obtained in 52 cases and further categorized into biopsies being supportive for patient management (including acute and chronic axonopathies and demyelinating neuropathies) and biopsies considered essential for patient management (including vasculitic neuropathies, leprous neuropathies, hereditary neuropathies, and chronic inflammatory demyelinating neuropathies). Nine nerve biopsies did not show any abnormal histopathological features, while 13 nerve biopsies were found to be inadequate for diagnosis, both these groups were categorized as noncontributory. With advanced nerve conduction studies available, nerve biopsy is losing its relevance. However, in our experience, nerve biopsy did complement the clinical findings and nerve conduction studies, with which a close correlation is required to make the histopathology of nerve biopsy more relevant in terms of guiding further specific workup and management.

Severe Muscle Weakness Needing Intubation in AIDS Patient

SESSION TITLE: Critical Care 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Flaccid paralysis has myriad of differential diagnoses ranging from different types of neuropathies, myopathies and neuromuscular disorders. HIV is now a chronic disease with the advent of highly active anti retroviral therapy (HAART) such that several HIV related complications are now evident. HIV myopathy is a rare condition that can manifest at any stage of HIV irrespective of the CD4 count. We present a case of HIV associated myopathy in a patient who presented with about 2-3 day history of generalized weakness. CASE PRESENTATION: A 41-year-old woman with HIV/AIDS who was non compliant with HAART presented with flaccid paralysis which progressed to respiratory failure requiring intubation and mechanical ventilation. Her CD4 count was 6/mcL with 75000 HIV RNA copies/ml. Cerebrospinal fluid analysis was negative for albumin-cytological dissociation. MRI brain and spine were negative for progressive multifocal leukoencephalopathy. MRI of bilateral lower extremities showed intramuscular edema. EMG/NCS was inconclusive in view of obesity and severe edema. Creatine kinase and aldolase were mildly elevated. Left quadriceps femoris biopsy was suggestive of occlusive small arteriopathy consistent with vasculitis, and severe myofiber atrophy. ANA, ANCA, CMV PCR, HTLV I/II were negative. She had similar presentation a year ago where she responded to steroids which were tapered over 8 months ago. She was diagnosed with AIDS at that time and started on HAART, however, patient was non compliant with treatment. This time however, she had minimal response to steroids and antiretroviral therapy. She had ATN and subsequent renal failure from multiple medications. Given her poor prognosis, comfort measures were initiated and patient passed away shortly after extubation. DISCUSSION: Neuromuscular disorders associated with HIV include neuropathies such as distal symmetric polyneuropathy, acute and chronic inflammatory demyelinating neuropathy, mononeuropathy, radiculopathy, etc., and myopathies.1 Muscle disorders in HIV could be from the virus itself resulting in HIV myopathy, which is similar in picture to autoimmune polymyositis; drug induced myopathy from HAART such as zidovudine which is a mitochondrial disorder; HIV wasting syndrome; myopathy from opportunistic infections such as CMV, etc. The biggest case series with HIV induced polymyositis had remission in 80% of patients at 9 month follow up.2 However this result has not been replicated and HIV myopathy is thought to have variable steroid response. CONCLUSIONS: HIV myopathy is a rare manifestation with variable prognosis and response to steroids. Immunosuppressive therapy is used with caution due to toxicity. Reference #1: Robinson-Papp J, Simpson DM. Neuromuscular diseases associated with HIV-1 infection. Muscle Nerve. 2009;40:1043-1053. Reference #2: Johnson RW, Williams FM, Kazi S, Dimachkie MM, Reveille JD. Human immunodeficiency virus-associated polymyositis: a longitudinal study of outcome. Arthritis Rheum. 2003;49:172-178. DISCLOSURE: The following authors have nothing to disclose: Pooja Gurram, Vikas Koppurapu, Krishna Siva Sai Kakkera, Kevin Davis, Swathi Subramany, Rajani Jagana No Product/Research Disclosure Information

Paraneoplastic neuropathies.

To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.

Severe refractory CIDP: a case series of 10 patients treated with bortezomib.

Treatment options for patients with aggressive chronic inflammatory demyelinating neuropathy are limited and include the anti-CD20 antibody rituximab and the immunosuppressive regime cyclophosphamide. We aimed to investigate retrospectively the efficacy of bortezomib, a proteasome inhibitor tackling highly metabolically active cell types such as plasma cells, in a case series of 10 treatment refractory CIDP patients. All patients reported showed a deterioration of the clinical CIDP scores under first-line treatment or escalating treatment with cyclophosphamide or rituximab. One or two cycles of bortezomib treatment (each cycle with 1.3mg/m2 administered s.c. on days 1, 4, 8, and 11) stabilized the majority of the patients (n=6) during treatment and even improved clinical and electrophysiological parameters of four patients up to 1year later. No relevant side-effects were reported. Two patients received autologous peripheral blood stem cell transplantation after bortezomib, which led to fatal infections. We conclude that bortezomib could be an attractive escalating treatment option with a good side-effect profile for patients with treatment refractory CIDP.

A comparative study of brachial plexus sonography and magnetic resonance imaging in chronic inflammatory demyelinating neuropathy and multifocal motor neuropathy.

To compare the performance of neuroimaging techniques, i.e. high-resolution ultrasound (HRUS) and magnetic resonance imaging (MRI), when applied to the brachial plexus, as part of the diagnostic work-up of chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy (MMN). Fifty-one incident, treatment-naive patients with CIDP (n = 23) or MMN (n = 28) underwent imaging of the brachial plexus using (i) a standardized MRI protocol to assess enlargement or T2 hyperintensity and (ii) bilateral HRUS to determine the extent of nerve (root) enlargement. We found enlargement of the brachial plexus in 19/51 (37%) and T2 hyperintensity in 29/51 (57%) patients with MRI and enlargement in 37/51 (73%) patients with HRUS. Abnormal results were only found in 6/51 (12%) patients with MRI and 12/51 (24%) patients with HRUS. A combination of the two imaging techniques identified 42/51 (83%) patients. We found no association between age, disease duration or Medical Research Council sum-score and sonographic nerve size, MRI enlargement or presence of T2 hyperintensity. Brachial plexus sonography could complement MRI in the diagnostic work-up of patients with suspected CIDP and MMN. Our results indicate that combined imaging studies may add value to the current diagnostic consensus criteria for chronic inflammatory neuropathies.