Showing papers by "University of Düsseldorf published in 2005"

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".

Abstract: New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer

Abstract: background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)

Diabetic neuropathies: a statement by the American Diabetes Association.

Abstract: The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. This statement is based on two recent technical reviews (1,2), to which the reader is referred for detailed discussion and relevant references to the literature. An internationally agreed simple definition of DPN for clinical practice is “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (3). However, the diagnosis cannot be made without a careful clinical examination of the lower limbs, as absence of symptoms should never be assumed to indicate an absence of signs. This definition conveys the important message that not all patients with peripheral nerve dysfunction have a neuropathy caused by diabetes. Confirmation can be established with …

Normal and pathological oscillatory communication in the brain

Abstract: The huge number of neurons in the human brain are connected to form functionally specialized assemblies. The brain's amazing processing capabilities rest on local communication within and long-range communication between these assemblies. Even simple sensory, motor and cognitive tasks depend on the precise coordination of many brain areas. Recent improvements in the methods of studying long-range communication have allowed us to address several important questions. What are the common mechanisms that govern local and long-range communication and how do they relate to the structure of the brain? How does oscillatory synchronization subserve neural communication? And what are the consequences of abnormal synchronization?

Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps

Abstract: Probabilistic maps of neocortical areas and subcortical fiber tracts, warped to a common reference brain, have been published using microscopic architectonic parcellations in ten human postmortem brains. The maps have been successfully applied as topographical references for the anatomical localization of activations observed in functional imaging studies. Here, for the first time, we present stereotaxic, probabilistic maps of the hippocampus, the amygdala and the entorhinal cortex and some of their subdivisions. Cytoarchitectonic mapping was performed in serial, cell-body stained histological sections. The positions and the extent of cytoarchitectonically defined structures were traced in digitized histological sections, 3-D reconstructed and warped to the reference space of the MNI single subject brain using both linear and non-linear elastic tools of alignment. The probability maps and volumes of all structures were calculated. The precise localization of the borders of the mapped regions cannot be predicted consistently by macroanatomical landmarks. Many borders, e.g. between the subiculum and entorhinal cortex, subiculum and Cornu ammonis, and amygdala and hippocampus, do not match sulcal landmarks such as the bottom of a sulcus. Only microscopic observation enables the precise localization of the borders of these brain regions. The superposition of the cytoarchitectonic maps in the common spatial reference system shows a considerably lower degree of intersubject variability in size and position of the allocortical structures and nuclei than the previously delineated neocortical areas. For the first time, the present observations provide cytoarchitectonically verified maps of the human amygdala, hippocampus and entorhinal cortex, which take into account the stereotaxic position of the brain structures as well as intersubject variability. We believe that these maps are efficient tools for the precise microstructural localization of fMRI, PET and anatomical MR data, both in healthy and pathologically altered brains.

Plasmacytoid predendritic cells initiate psoriasis through interferon-α production

Abstract: Psoriasis is one of the most common T cell-mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis.

Mechanical properties of ultrahigh-strength gold nanowires

Abstract: Nanowires have attracted considerable interest as nanoscale interconnects and as the active components of both electronic and electromechanical devices. Nanomechanical measurements are a challenge, but remain key to the development and processing of novel nanowire-based devices. Here, we report a general method to measure the spectrum of nanowire mechanical properties based on nanowire bending under the lateral load from an atomic force microscope tip. We find that for Au nanowires, Young's modulus is essentially independent of diameter, whereas the yield strength is largest for the smallest diameter wires, with strengths up to 100 times that of bulk materials, and substantially larger than that reported for bulk nanocrystalline metals (BNMs)1,2,3,4,5. In contrast to BNMs, nanowire plasticity is characterized by strain-hardening, demonstrating that dislocation motion and pile-up is still operative down to diameters of 40 nm. Possible origins for the different mechanical properties of nanowires and BNMs are discussed.

The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games

Abstract: The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunbiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed.

Geographic routing in city scenarios

Abstract: Position-based routing, as it is used by protocols like Greedy Perimeter Stateless Routing (GPSR) [5], is very well suited for highly dynamic environments such as inter-vehicle communication on highways. However, it has been discussed that radio obstacles [4], as they are found in urban areas, have a significant negative impact on the performance of position-based routing. In prior work [6] we presented a position-based approach which alleviates this problem and is able to find robust routes within city environments. It is related to the idea of position-based source routing as proposed in [1] for terminode routing. The algorithm needs global knowledge of the city topology as it is provided by a static street map. Given this information the sender determines the junctions that have to be traversed by the packet using the Dijkstra shortest path algorithm. Forwarding between junctions is then done in a position-based fashion. In this short paper we show how position-based routing can be aplied to a city scenario without assuming that nodes have access to a static street map and without using source routing.

The Genome of the Basidiomycetous Yeast and Human Pathogen Cryptococcus Neoformans

Abstract: Cryptococcus neoformans is a basidionnycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its similar to20-megabase genome, which contains similar to6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions. The presence of these transposons may drive karyotype instability and phenotypic variation. C. neoformans encodes unique genes that may contribute to its unusual virulence properties, and comparison of two phenotypically distinct strains reveals variation in gene content in addition to sequence polymorphisms between the genomes.

Infections in patients with rheumatoid arthritis treated with biologic agents.

Abstract: Objective To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment Methods Patients enrolled in the German biologics register between May 2001 and September 2003 were included Treating rheumatologists assessed adverse events and serious adverse events All adverse events and serious adverse events experienced within 12 months after study entry were analyzed Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics Results Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs The total number of adverse events per 100 patient-years was 226 (95% confidence interval [95% CI] 187–272) among patients receiving etanercept, 283 (95% CI 231–347) among patients receiving infliximab, and 68 (95% CI 50–94) among controls (P < 00001) Significant differences in the rate of serious adverse events were also observed For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 64 (95% CI 45–91), 62 (95% CI 40–95), and 23 (95% CI 13–39), respectively (P = 00016) After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 22 (95% CI 09–54) for patients receiving etanercept and 21 (95% CI 08–55) for patients receiving infliximab, compared with controls Conclusion Patients treated with biologic agents have a higher a priori risk of infection However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors

Impaired Memory Retrieval after Psychosocial Stress in Healthy Young Men

Abstract: Glucocorticoids (GCs) are known to modulate memory in animals and humans. One popular model suggests that stress or GC treatment enhances memory consolidation while impairing delayed memory retrieval. Studies in humans have documented that treatment with GCs impairs delayed memory retrieval. Similar alterations after exposure to stress have not been observed thus far. In the present study, 19 young healthy male subjects were exposed to either a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control condition in a crossover manner. After both treatments, retrieval of a word list (learned 24 h earlier) containing 10 neutral, 10 negative, and 10 positive words was tested. The stressor induced a significant increase in salivary free cortisol and a decrease in mood. Memory retrieval (free recall) was significantly impaired after the stress condition. Follow-up analysis revealed that negative and positive words (i.e., emotionally arousing words) were affected, whereas no effect was observed for neutral words. No changes were detected for cued recall, working memory, or attention. The present study thus demonstrates that psychosocial stress impairs memory retrieval in humans and suggests that emotionally arousing material is especially sensitive to this effect.

The emerging biology of the nitrite anion

Abstract: Nitrite has now been proposed to play an important physiological role in signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics.

Parallel Patterns of Evolution in the Genomes and Transcriptomes of Humans and Chimpanzees

Abstract: The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.

B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator.

Abstract: B and T lymphocyte attenuator (BTLA) provides an inhibitory signal to B and T cells. Previously, indirect observations suggested that B7x was a ligand for BTLA. Here we show that BTLA does not bind B7x; instead, we identify herpesvirus entry mediator (HVEM) as the unique BTLA ligand. BTLA bound the most membrane-distal cysteine-rich domain of HVEM, distinct from regions where the ligands LIGHT and lymphotoxin-α bound HVEM. HVEM induced BTLA tyrosine phosphorylation and association of the tyrosine phosphatase SHP-2 and repressed antigen-driven T cell proliferation, providing an example of reverse signaling to a non–tumor necrosis factor family ligand. The conservation of the BTLA-HVEM interaction between mouse and human suggests that this system is an important pathway regulating lymphocyte activation and/or homeostasis in the immune response.

Unexpected complexity of the Wnt gene family in a sea anemone

Abstract: The Wnt gene family encodes secreted signalling molecules that control cell fate in animal development and human diseases. Despite its significance, the evolution of this metazoan-specific protein family is unclear. In vertebrates, twelve Wnt subfamilies were defined, of which only six have counterparts in Ecdysozoa (for example, Drosophila and Caenorhabditis). Here, we report the isolation of twelve Wnt genes from the sea anemone Nematostella vectensis, a species representing the basal group within cnidarians. Cnidarians are diploblastic animals and the sister-group to bilaterian metazoans. Phylogenetic analyses of N. vectensis Wnt genes reveal a thus far unpredicted ancestral diversity within the Wnt family. Cnidarians and bilaterians have at least eleven of the twelve known Wnt gene subfamilies in common; five subfamilies appear to be lost in the protostome lineage. Expression patterns of Wnt genes during N. vectensis embryogenesis indicate distinct roles of Wnts in gastrulation, resulting in serial overlapping expression domains along the primary axis of the planula larva. This unexpectedly complex inventory of Wnt family signalling factors evolved in early multi-cellular animals about 650 million years (Myr) ago, predating the Cambrian explosion by at least 100 Myr (refs 5, 8). It emphasizes the crucial function of Wnt genes in the diversification of eumetazoan body plans.

Lower Cancer Incidence in Amsterdam-I Criteria Families Without Mismatch Repair Deficiency: Familial Colorectal Cancer Type X

Abstract: ContextApproximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown.ObjectiveTo determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities.Design, Setting, and ParticipantsIdentification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses.Main Outcome MeasuresCancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data.ResultsGroup A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001).ConclusionsFamilies who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of “familial colorectal cancer type X” is suggested to describe this type of familial aggregation of colorectal cancer.

Language Contact and Grammatical Change

Abstract: The phenomenon of language contact, and how it affects the structure of languages, has been of great interest to linguists. This study looks at how grammatical forms and structures evolve when speakers of two languages come into contact, and offers an interesting insight into the mechanism that induces people to transfer grammatical structures from one language to another. Drawing on findings from languages all over the world, Language Contact and Grammatical Change shows that the transfer of linguistic material across languages is quite regular and follows universal patterns of grammaticalization - contrary to previous claims that it is a fairly irregular process - and argues that internal and external explanations of language structure and change are in no way mutually exclusive. Engaging and informative, this book will be of great interest to sociolinguists, linguistic anthropologists, and all those working on grammaticalization, language contact, and language change.

Nutritional, dietary and postprandial oxidative stress

Abstract: Nutritional, or dietary oxidative stress denotes a disturbance of the redox state resulting from excess oxidative load or from inadequate nutrient supply favoring prooxidant reactions. Low intake or impaired availability of dietary antioxidants including vitamins E and C, carotenoids, polyphenols, and other micronutrients (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress, as a subform of nutritional oxidative stress, ensues from sustained postprandial hyperlipidemia and/or hyperglycemia and is associated with a higher risk for atherosclerosis, diabetes, and obesity. In Western societies, a significant part of the day is spent in the postprandial state. Unsaturated fatty acids incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid hydroperoxides present in the diet are absorbed, contributing to the prooxidant load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent vasodilation is impaired in the postprandial state, making postprandial oxidative stress an important factor modulating cardiovascular risk. Postprandial oxidative stress is attenuated when dietary antioxidants are supplied together with a meal rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g., from wine, cocoa, or tea, improves endothelial dysfunction and lowers the susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial function not solely as antioxidants but also as modulatory signaling molecules.

Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues

Abstract: Mammalian tissues produce nitric oxide (NO) to modify proteins at heme and sulfhydryl sites, thereby regulating vital cell functions. The majority of NO produced is widely assumed to be neutralized into supposedly inert oxidation products including nitrite (NO2(-)). Here we show that nitrite, also ubiquitous in dietary sources, is remarkably efficient at modifying the same protein sites, and that physiological nitrite concentrations account for the basal levels of these modifications in vivo. We further find that nitrite readily affects cyclic GMP production, cytochrome P450 activities, and heat shock protein 70 and heme oxygenase-1 expression in a variety of tissues. These cellular activities of nitrite, combined with its stability and abundance in vivo, suggest that this anion has a distinct and important signaling role in mammalian biology, perhaps by serving as an endocrine messenger and synchronizing agent. Thus, nitrite homeostasis may be of great importance to NO biology.

Definition and prevalence of subfertility and infertility.

Abstract: A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.

Photosystem II core phosphorylation and photosynthetic acclimation require two different protein kinases

Abstract: Illumination changes elicit modifications of thylakoid proteins and reorganization of the photosynthetic machinery. This involves, in the short term, phosphorylation of photosystem II (PSII) and light-harvesting (LHCII) proteins. PSII phosphorylation is thought to be relevant for PSII turnover, whereas LHCII phosphorylation is associated with the relocation of LHCII and the redistribution of excitation energy (state transitions) between photosystems. In the long term, imbalances in energy distribution between photosystems are counteracted by adjusting photosystem stoichiometry. In the green alga Chlamydomonas and the plant Arabidopsis, state transitions require the orthologous protein kinases STT7 and STN7, respectively. Here we show that in Arabidopsis a second protein kinase, STN8, is required for the quantitative phosphorylation of PSII core proteins. However, PSII activity under high-intensity light is affected only slightly in stn8 mutants, and D1 turnover is indistinguishable from the wild type, implying that reversible protein phosphorylation is not essential for PSII repair. Acclimation to changes in light quality is defective in stn7 but not in stn8 mutants, indicating that short-term and long-term photosynthetic adaptations are coupled. Therefore the phosphorylation of LHCII, or of an unknown substrate of STN7, is also crucial for the control of photosynthetic gene expression.

Chronic Inflammatory Demyelinating Polyneuropathy

Abstract: Approximately 3% of inflammatory demyelinating polyneuropathy cases progress for longer than 4 weeks, the arbitrary cut-off point for the diagnosis of GBS, or they relapse and fluctuate. Such cases are referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). In CIDP, the nadir of illness is usually reached after several months, either after a chronic monophasic, a stepwise progressing, or a relapsing course. In contrast, the even rarer recurrent GBS, in which acute relapses appear after complete recovery, is usually considered to be more closely tied to GBS than to CIDP by most authorities, since time course and treatment response of single recurrences are identical to typical monophasic GBS.