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61-446: In its traditional manifestation, chronic inflammatory demyelinating polyneuropathy is characterized by symmetric, progressive limb weakness and sensory loss, which typically starts in the legs. Patients report having trouble getting out of a chair, walking, climbing stairs, and falling. Problems with gripping objects, tying shoe laces, and using utensils can all be brought on by upper limb involvement. Proximal limb weakness

122-431: A flow of electrical impulses from the brain , which signals them to contract through the release of calcium by the sarcoplasmic reticulum . Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This makes less calcium available for

183-436: A high-frequency signal . After an extended period of maximum contraction, the nerve's signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply 'stop listening' and gradually cease to move, often lengthening . As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness following

244-458: A drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach. Ciclosporin is thought to bind to immunocompetent lymphocytes , especially T-lymphocytes . Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In

305-442: A force far below what a muscle could potentially generate, and barring pathology , neuromuscular fatigue is seldom an issue. For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice strength trainers , the muscle's ability to generate force is most strongly limited by nerve's ability to sustain

366-492: A lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so. In some conditions, such as myasthenia gravis , muscle strength is normal when resting, but true weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of Myalgic encephalomyelitis/chronic fatigue syndrome , where objective post-exertion muscle weakness with delayed recovery time has been measured and

427-424: A local, muscle-specific inability to do work. Neuromuscular fatigue can be either central or peripheral. The central fatigue is generally described in terms of a reduction in the neural drive or nerve-based motor command to working muscles that results in a decline in the force output. It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if

488-450: A metabolic byproduct. Contrary to common belief, lactic acid accumulation doesn't actually cause the burning sensation felt when people exhaust their oxygen and oxidative metabolism, but in actuality, lactic acid in presence of oxygen recycles to produce pyruvate in the liver, which is known as the Cori cycle . Substrates produce metabolic fatigue by being depleted during exercise, resulting in

549-401: A patient presents with a non-length-dependent demyelinating polyneuropathy which either develops chronically over several months or progresses over more than a month, CIDP may be diagnosed. There may be a secondary progressive course along with a progressive course that follows, or it may be relapsing and remitting. Pathological investigations and electrophysiological studies, if necessary, show

610-552: A precise estimation of its clinical efficacy for CIDP is not available, as randomized controlled trials (RCT) have not been performed. (In MS, the ASTIMS RCT provides evidence for superior effect of HSCT to the then-best practice for treatment of aggressive MS. The more recent MIST RCT confirmed its superiority in MS.) Physical therapy and occupational therapy may improve muscle strength, activities of daily living , mobility, and minimize

671-527: A range of organisations under the umbrella of EPODIN (European Patient Organization for Disimmune & Inflammatory Neuropathies) As in multiple sclerosis , another demyelinating condition, it is not possible to predict with certainty how CIDP will affect patients over time. The pattern of relapses and remissions varies greatly with each patient. A period of relapse can be very disturbing, but many patients make significant recoveries. If diagnosed early, initiation of early treatment to prevent loss of nerve axons

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732-400: A rare chronic ataxic neuropathy linked to disialosyl ( ganglioside ) antibodies, IgM paraprotein , ophthalmoplegia , and cold agglutinins . CIDP variants are among several types of immune-mediated neuropathies recognised. These include: Other possible diagnoses are For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations. The diagnosis

793-436: A response have been found in chronic inflammatory demyelinating polyneuropathy. Individuals with chronic inflammatory demyelinating polyneuropathy have evidence of activation of T cells in the systemic immune compartment; however, antigen specificity is still largely unknown. It was proposed more than 20 years ago that autoantibodies play a role in the development of chronic inflammatory demyelinating polyneuropathy. This

854-463: A subgroup of inflammatory neuropathies with IgG4 autoantibodies against the paranodal proteins neurofascin -155, contactin -1 and caspr -1. These cases are special not only because of their pathology, but also because they are non-responsive to the standard treatment. They are responsive to Rituximab instead. Also some cases of combined central and peripheral demyelination (CCPD) could be produced by neurofascins. Autoantibodies to components of

915-462: Is a feature of some of the published definitions. Asthenia or asthaenia ( Greek : ἀσθένεια , literally lack of strength but also disease ) is a medical term referring to a condition in which the body lacks or has lost strength either as a whole or in any of its parts. It is a poorly defined condition that can include true or primary muscle weakness or perceived muscle weakness. For perceived muscle weakness, asthenia has been described as

976-453: Is a fundamental clinical characteristic that sets apart chronic inflammatory demyelinating polyneuropathy from the vast majority of distal polyneuropathies , which are far more common. Proprioception impairment, distal paresthesias , loss of feeling, and poor balance are all brought on by sensory involvement. Only a small percentage of cases involve neuropathic pain . Fatigue has been identified as common in CIDP patients, but it

1037-621: Is a lack of muscle strength. The causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular diseases , such as myasthenia gravis. Perceived muscle weakness occurs in diseases such as sleep disorders, and depression. Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle fatigue manifests as an overall sense of energy deprivation, and peripheral muscle weakness manifests as

1098-408: Is a source of energy. The fundamental difference between the peripheral and central theories of muscle fatigue is that the peripheral model of muscle fatigue assumes failure at one or more sites in the chain that initiates muscle contraction. Peripheral regulation therefore depends on the localized metabolic chemical conditions of the local muscle affected, whereas the central model of muscle fatigue

1159-606: Is a symmetrical polyneuropathy that affects the proximal and distal muscles equally. Atypical cases of CIDP include multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), Lewis-Sumner syndrome (LSS), and distal acquired demyelinating symmetric (DADS). DADS is a sensory or sensorimotor neuropathy that is symmetrical and length-dependent. It is frequently linked to an IgM paraprotein and noticeably longer distal motor latencies. The characteristics are typical of demyelinating neuropathy with antimyelin-associated glycoprotein (MAG) antibodies; however, anti-MAG neuropathy

1220-549: Is also a side effect of some medications and treatments, such as Ritonavir (a protease inhibitor used in HIV treatment). Differentiating psychogenic (perceived) asthenia and true asthenia from myasthenia is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness. Myasthenia or myasthaenia (my- from Greek : μυο meaning "muscle" + -asthenia [ ἀσθένεια ] meaning "weakness"), or simply muscle weakness,

1281-410: Is always a noticeable difference in the compound muscle action potential's dispersion, and conduction block is commonly experienced. An MRI can show proximal nerve or root enlargement and gadolinium enhancement, which indicate active inflammation as well as demyelination in the brachial plexus or cauda equina . Clinically, CIDP is divided into "typical" and "atypical" cases. A typical case of CIDP

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1342-411: Is an integrated mechanism that works to preserve the integrity of the system by initiating muscle fatigue through muscle derecruitment, based on collective feedback from the periphery, before cellular or organ failure occurs. Therefore, the feedback that is read by this central regulator could include chemical and mechanical as well as cognitive cues. The significance of each of these factors will depend on

1403-463: Is considered a rare disease with only 50 cases reported up to 2004. A total of 90 cases had been reported by 2009. The National Vaccine Injury Compensation Program has awarded money damages to patients who came down with CIDP after receiving one of the childhood vaccines listed on the Federal Government's vaccine injury table . These Vaccine Court awards often come with language stating that

1464-740: Is currently intravenous immunoglobulin and other treatments include corticosteroids (e.g., prednisone ), and plasmapheresis (plasma exchange) which may be prescribed alone or in combination with an immunosuppressant drug . Recent controlled studies show subcutaneous immunoglobulin appears to be as effective for CIDP treatment as intravenous immunoglobulin in most patients, and with fewer systemic side effects. Intravenous immunoglobulin and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. Intravenous immunoglobulin

1525-671: Is extremely rare but under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is favoured in preventing irreversible axonal loss and improving functional recovery. There is a lack of awareness and treatment of CIDP. Although there are stringent research criteria for selecting patients for clinical trials, there are no generally agreed-upon clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of

1586-496: Is important because multifocal motor neuropathy responds to intravenous immunoglobulin alone, while chronic inflammatory demyelinating polyneuropathy responds to intravenous immunoglobulin, steroids and plasma exchange. It has been suggested that multifocal motor neuropathy is distinct from chronic inflammatory demyelinating polyneuropathy and that Lewis-Sumner syndrome is a distinct variant type of chronic inflammatory demyelinating polyneuropathy. The Lewis-Sumner form of this condition

1647-547: Is not included in the CIDP criteria according to the EFNS/PNS criteria, primarily due to the presence of a particular antibody and a different response to treatment. LSS exhibits a multifocal distribution, with conduction block serving as the disease's electrophysiological hallmark. Furthermore, there have been reports of pure motor and sensory CIDP variants, with the latter occasionally limited to sensory nerve roots (chronic immune sensory polyradiculopathy). The acronym CANOMAD refers to

1708-436: Is not yet understood. The gene product was initially identified as a 190-kD protein associated with the contactin-PTPRZ1 complex. The 1,384- amino acid protein, also designated p190 or CASPR for 'contactin-associated protein,' includes an extracellular domain with several putative protein-protein interaction domains, a putative transmembrane domain, and a 74-amino acid cytoplasmic domain. Northern blot analysis showed that

1769-424: Is probably the first-line CIDP treatment, but is extremely expensive. For example, in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $ 8,000 just for the immunoglobulin—not including other charges such as nurse administration. Immunosuppressive drugs are often of the cytotoxic ( chemotherapy ) class, including rituximab (Rituxan) which targets B cells , and cyclophosphamide ,

1830-486: Is recommended. However, many individuals are left with residual numbness, weakness, tremors, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life . It is important to build a good relationship with doctors, both primary care and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of

1891-655: Is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody. Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials. A review of several treatments found that azathioprine, interferon alpha and methotrexate were not effective. Cyclophosphamide and rituximab seem to have some response. Mycophenolate mofetil may be of use in milder cases. Immunoglobulin and steroids are

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1952-433: Is unclear how much this is due to primary (due to the disease action on the body) or secondary effects (impacts on the whole person of being ill with CIDP). Numerous reports have outlined a range of clinical patterns that are thought to be chronic inflammatory demyelinating polyneuropathy variations. Different variations include ataxic, pure motor, and pure sensory patterns; additionally, there are multifocal patterns in which

2013-518: Is usually provisionally made through a clinical neurological examination . Typical diagnostic tests include: In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy. First-line treatment for CIDP

2074-512: The neurexin family of proteins, hence its another name " Neurexin IV ". CASPR is a membrane protein found in the neuronal membrane in the paranodal section of the axon[[]] in myelinated neurons, between the Nodes of Ranvier containing Na+ channels, and juxtaparanode , which contains K+ channels. During myelination, caspr associates with contactin in a cis complex, though its precise role in myelination

2135-427: The sliding filament model . Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of glucose , used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid as

2196-511: The Court denies that the specific vaccine "caused petitioner to suffer CIDP or any other injury. Nevertheless, the parties agree to the joint stipulation, attached hereto as Appendix A. The undersigned finds said stipulation reasonable and adopts it as the decision of the Court in awarding damages, on the terms set forth therein." A keyword search on the Court of Federal Claims "Opinions/Orders" database for

2257-527: The Ranvier nodes, specially autoantibodies the Contactin-associated protein 1 ( CASPR ), cause a form of CIDP with an acute " Guillain-Barre -like" phase, followed by a chronic phase with progressive symptoms. Different IgG subclasses are associated with the different phases of the disease. IgG3 Caspr autoantibodies were found during the acute GBS-like phase, while IgG4 Caspr autoantibodies were present during

2318-416: The U.S., these drugs are used "off-label", meaning that they do not have an indication for the treatment of CIDP in their package inserts. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used. Anti-thymocyte globulin , an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin

2379-450: The ability of Ca to stimulate actin and myosin to contract. CASPR 8506 53321 ENSG00000108797 ENSMUSG00000017167 P78357 O54991 NM_003632 NM_016782 NP_003623 NP_058062 CASPR also known as Contactin associated protein 1 , Paranodin and CASPR1 is a protein that in humans is encoded by the CNTNAP1 gene . CASPR is a part of

2440-446: The arms with multifocal involvement of peripheral nerves. Also in 1982 Dyck et al reported a response to prednisolone to a condition they referred to as chronic inflammatory demyelinating polyradiculoneuropathy. Parry and Clarke in 1988 described a neuropathy which was later found to be associated with IgM autoantibodies directed against GM1 gangliosides. This latter condition was later termed multifocal motor neuropathy This distinction

2501-527: The chronic phase of disease. In the local tissue compartment of peripheral nerves , the immune system is carefully regulated by a normal, balanced collection of immunocompetent cells as well as soluble factors, maintaining the integrity of the system. Maintaining self-tolerance requires defense against immune reactions to autoantigens . Chronic inflammatory demyelinating polyneuropathy disrupts self-tolerance and activates autoreactive T and B cells , which are normally suppressed immune cells . This leads to

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2562-553: The distributions of specific nerve territories experience weakness and sensory loss. Chronic inflammatory demyelinating polyneuropathy (or polyradiculoneuropathy) is considered an autoimmune disorder destroying myelin, the protective covering of the nerves. Typical early symptoms are "tingling" (sort of electrified vibration or paresthesia ) or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations , "vibration" feelings, loss of balance, general muscle cramping and nerve pain. CIDP

2623-438: The eventual reduction or lack of ability of a single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-optimal aerobic metabolism , generally results in the accumulation of lactic acid and other acidic anaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue, though recent studies have indicated otherwise, actually finding that lactic acid

2684-418: The factor limiting contractile force. Peripheral muscle fatigue during physical work is considered an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigue—affecting a national average of 72% of adults in the work force in 2002. This causes contractile dysfunction that manifests in

2745-534: The feeling of weak or tired muscles in the absence of muscle weakness, that is the muscle can generate a normal amount of force but it is perceived as requiring more effort. General asthenia occurs in many chronic wasting diseases (such as tuberculosis and cancer), sleep disorders or chronic disorders of the heart, lungs or kidneys, and is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certain organs or systems of organs, as in asthenopia , characterized by ready fatiguability. Asthenia

2806-430: The first line choices for treatment. In severe cases of CIDP, when second-line immunomodulatory drugs are not efficient, autologous hematopoietic stem cell transplantation (HSCT) is sometimes performed. The treatment may induce long-term remission even in severe treatment-refractory cases of CIDP. To improve outcome, it has been suggested that it should be initiated before irreversible axonal damage has occurred. However,

2867-655: The gene is transcribed predominantly in brain as a transcript of 6.2 kb, with weak expression in several other tissues tested. The architecture of its extracellular domain is similar to that of neurexins , and this protein may be the signaling subunit of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. [provided by RefSeq, Jan 2009]. Mutations in CNTNAP1 cause arthrogryposis multiplex congenita . Other diseases associated with mutations in this gene include lethal congenital contracture syndrome type 7 and congenital hypomyelinating neuropathy type 3. This article incorporates text from

2928-443: The majority of HIV-CIDP cases. Pregnancy has been linked to a significantly greater risk of relapse. In one study, 32% of 92 CIDP patients had a history of infection within 6 weeks of the onset of neurological symptoms, with the majority of these infections being non-specific upper respiratory tract or gastrointestinal infections. A different study showed that out of 100 patients, 16% had an infectious event six weeks or less prior to

2989-474: The muscle cell. In addition, the Columbia researchers propose that an enzyme activated by this released calcium eats away at muscle fibers. Substrates within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate . ATP binds to the myosin head and causes the 'ratchetting' that results in contraction according to

3050-443: The nature of the fatigue-inducing work that is being performed. Though not universally used, "metabolic fatigue" is a common alternative term for peripheral muscle weakness, because of the reduction in contractile force due to the direct or indirect effects of the reduction of substrates or accumulation of metabolites within the myocytes . This can occur through a simple lack of energy to fuel contraction, or through interference with

3111-444: The onset of neurological symptoms: seven patients had CIDP that was related to or followed viral hepatitis , and six had a chronic infection with the hepatitis B virus . The other nine patients had vague symptoms similar to the flu. There is no known genetic predisposition to chronic inflammatory demyelinating polyneuropathy. Some variants of CIDP present autoimmunity against proteins of the node of Ranvier . These variants comprise

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3172-424: The organ-specific damage typical of autoimmune disease . Molecular mimicry may be particularly relevant to the tolerance breakdown linked to autoimmune neuropathies. The process known as " molecular mimicry " occurs when an infectious organism that shares epitopes from its host's afflicted tissue triggers an immune response in the host. However, only a small number of convincingly identified specific targets for such

3233-418: The present research criteria to routine clinical practice often misses the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease. HIV infection is a factor in the occurrence of CIDP. At every stage of HIV infection, distinct patterns of CIDP, whether progressive or relapsing, have been noted. Increased protein content is linked to CSF pleocytosis in

3294-475: The root cause of chronic inflammatory demyelinating polyneuropathy. Apart from myelin-directed antibodies, other serum components that can cause demyelination as well as conduction block include complement, cytokines , and other inflammatory mediators. Individuals with chronic inflammatory demyelinating polyneuropathy have a low frequency of specific antibodies, which suggests that different antibodies and different mechanisms are involved in each patient. When

3355-634: The shrinkage of muscles and tendons and distortions of the joints. Ongoing specialist community support, information, advice, and guidance is available from a range of Charities , Non-Government Organisations (NGOs), and Patient Advisory Groups around the world. In the United Kingdom this is provided by GAIN (Guillain–Barré and Associated Inflammatory Neuropathies), in the USA it is provided by GBS/CIDP Foundation International, and in The European Union by

3416-527: The term "CIDP" returns 202 opinions related to CIDP and vaccine injury compensation. Weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy . It occurs in neuromuscular junction disorders, such as myasthenia gravis . Muscle cells work by detecting

3477-407: The underlying demyelinating process. The primary basis for diagnosing CIDP is the electrophysiological studies that depict an asymmetric demyelinating process. Comparison of the proximal and distal latencies of equivalent segments of two nerves in the same limb reveals that these patients with acquired demyelinating neuropathy frequently have a differential slowing of conduction velocity. There

3538-404: The variability in severity and progression of the disease, doctors will not be able to give a definite prognosis. A period of experimentation with different treatment regimens is likely to be necessary in order to discover the most appropriate treatment regimen for a given patient. In 1982 Lewis et al. reported a group of patients with a chronic asymmetrical sensorimotor neuropathy mostly affecting

3599-434: The work was continued at the same intensity. The exact mechanisms of central fatigue are unknown, though there has been considerable interest in the role of serotonergic pathways. Nerves control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences synaptic fatigue it becomes unable to stimulate the muscle that it innervates. Most movements require

3660-540: The workout. Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force. It is this "neural training" that causes several weeks worth of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit. Past this point, training effects increase muscular strength through myofibrillar or sarcoplasmic hypertrophy and metabolic fatigue becomes

3721-589: Was supported by the detection of oligoclonal IgG bands in the cerebrospinal fluid and immunoglobulin as well as complement deposition on myelinated nerve fibers. Target antigens may also include gangliosides and related glycolipids . There is serologic evidence of recent Campylobacter jejuni infection in a small number of individuals with chronic inflammatory demyelinating polyneuropathy. Because carbohydrate epitopes are expressed in both microbial lipopolysaccharides and nerve glycolipids , this discovery may, in rare cases, point to molecular mimicry as

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