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Despite the fact that there are published case reports and model work providing evidence of inflammation in Charcot–Marie–Tooth disorders (CMTs), in clinical practice, CMT and inflammatory neuropathies are always classified as two separate groups of disorders. This sharp separation of chronic neuropathies into two groups has serious clinical implications. As a consequence, the patients harboring CMT mutations are practically excluded from pharmacological anti-inflammatory treatments. In this review, we present that neuropathological studies of peripheral nerves taken from some patients representing familial aggregation of CMTs revealed the presence of inflammation within the nerves. This shows that neurodegeneration resulting from germline mutations and the inflammatory process are not mutually exclusive. We also point to reports demonstrating that, at the clinical level, a positive response to anti-inflammatory therapy was observed in some patients diagnosed with CMTs, confirming the role of the inflammatory component in CMT. We narrowed a group of more than 100 genes whose mutations were found in CMT-affected patients to the seven most common (MPZ, PMP22, GJB1, SEPT9, LITAF, FIG4, and GDAP1) as being linked to the coexistence of hereditary and inflammatory neuropathy. We listed studies of mouse models supporting the idea of the presence of an inflammatory process in some CMTs and studies demonstrating at the cellular level the presence of an inflammatory response. In the following, we discuss the possible molecular basis of some neuropathies involving neurodegenerative and inflammatory processes at both the clinical and morphological levels. Finally, we discuss the prospect of a therapeutic approach using immunomodulation in some patients affected by CMTs. [ABSTRACT FROM AUTHOR]

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a "double‐edged sword" as the use of ICIs caused multiple immune‐related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain–Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function‐related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI‐induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy. [ABSTRACT FROM AUTHOR]

The nodes of Ranvier (NoR) are essential domains for nerve conduction and their disruption plays a key role in the pathophysiology of immune‐mediated neuropathies. Our understanding of the specialized nodal regions and the immune mechanisms that affect them is growing and has led to the update of peripheral neuropathy classification to include the autoimmune nodopathies, defined by the site of the autoimmune attack. Autoantibodies directed against molecules of the nodal region (as neurofascin‐140/186, neurofascin‐155, contactin‐1, contactin‐associated protein 1, contactin‐associated protein 2, gangliosides, LGI4, or myelin‐associated glycoprotein), macrophage‐induced paranodal demyelination, and phenotypic changes of the nodal domains of Schwann cells have been identified as key mechanisms in the pathogenesis of the autoimmune neuropathies. This review explores the current knowledge of the autoimmune vulnerability of the NoR, including the underlying mechanisms leading to dysfunction in the diverse autoimmune disorders. [ABSTRACT FROM AUTHOR]

Guillain Barré syndrome (GBS) functional assessment is necessary in clinical practice, research and clinical trials. Existing instruments are not sensitive to change and are not applicable to the current GBS clinical spectrum. To construct a functional assessment for acute inflammatory neuropathies (FAAIN-GBS), inclusive for current GBS spectrum that assesses extension and intensity separately. FAAIN-GBS subscales were constructed. Its structure and interpretation were defined. It was validated using data from medical record of 167 GBS patients admitted to the Institute of Neurology and Neurosurgery. Cronbach α was used for items reduction and reliability analysis. Bartlett sphericity test was performed. Exploratory factor analysis (EFA) of the main components, with varimax rotation, was applied to evaluate dimensionality and content validity. Hughes scale was used as gold standard for criterion validity. Sensitivity, specificity and area under the receiver operating characteristic curves (AUROC), were calculated. Construct validity was assessed by confirmatory factor analysis (CFA). FAAIN-GBS is made up of two subscales (extension and intensity). The final score is obtained by averaging both dimensions. Internal consistency was acceptable (Cronbach 0.745). EFA showed three dimensions: intensity, spinal extension and cranial extension. Spearman correlation between FAAIN-GBS and Hughes scale was 0.463. Sensitivity (0.714) and specificity (0.986) values showed the good behavior of the scale; AUROC was 0.93. FAAIN-GBS was constructed and a first step of validation was made, showing good internal consistency and validity. New prospective studies with large populations will be necessary to perfect this instrument that could be useful in neurological practice. [ABSTRACT FROM AUTHOR]

Abstract Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic inflammatory neuropathy. CIDP is diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria, which combine clinical features with the electrophysiological evidence of demyelination. However, firstly, diagnosis is challenging, as some patients e.g. with severe early axonal damage do not fulfil the criteria. Secondly, objective and reliable tools to monitor the disease course are lacking. Thirdly, about 25% of CIDP patients do not respond to evidence-based first-line therapy. Recognition of these patients is difficult and treatment beyond first-line therapy is based on observational studies and case series only. Individualized immunomodulatory treatment does not exist due to the lack of understanding of essential aspects of the underlying pathophysiology. Novel diagnostic imaging techniques and molecular approaches can help to solve these problems but do not find enough implementation. This review gives a comprehensive overview of novel diagnostic techniques and monitoring approaches for CIDP and how these can lead to individualized treatment and better understanding of pathophysiology.

Summary: Inflammatory neuropathies are a heterogeneous group of rare diseases of the peripheral nervous system that include acute and chronic diseases, such as Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The etiology and pathophysiological mechanisms of inflammatory neuropathies are only partly known, but are considered autoimmune disorders in which an aberrant immune response, including cellular and humoral components, is directed towards components of the peripheral nerve causing demyelination and axonal damage. Therapy of these disorders includes broad-spectrum immunomodulatory and immunosuppressive treatments, such as intravenous immunoglobulin, corticosteroids, or plasma exchange. However, a significant proportion of patients do not respond to any of these therapies, and treatment selection is not optimized according to disease pathophysiology. Therefore, research on disease pathophysiology aiming to reveal clinically and functionally relevant disease mechanisms and the development of new treatment approaches are needed to optimize disease outcomes in CIDP and GBS. This topical review describes immunological progress that may help guide therapeutic strategies in the future in these two disorders. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune-mediated inflammatory disease of the peripheral nervous system characterized by a response directed against certain myelin proteins and for which therapies are limited. Previous studies have suggested a beneficial role of FTY720, a sphingosine 1-phosphate (S1P) receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes, in the treatment of experimental autoimmune neuritis (EAN). Therefore, we investigated whether FTY720 is also beneficial in chronic experimental autoimmune neuritis (c-EAN), a recently developed rat model mimicking human CIDP. Methods c-EAN was induced in Lewis rats by immunization with S-palm P0(180–199) peptide. Rats were treated with FTY720 (1 mg/kg) or vehicle intraperitoneally once daily from the onset of clinical signs for 18 days; clinical signs were assessed daily until 60 days post-immunization (dpi). Electrophysiological and histological features were examined at different time points. We also evaluated the serum levels of different pro- and anti-inflammatory cytokines by ELISA or flow cytometry at 18, 40, and 60 dpi. Results Our data demonstrate that FTY720 decreased the severity and abolished the chronicity of the disease in c-EAN rats. Therapeutic FTY720 treatment reversed electrophysiological and histological anomalies, suggesting that myelinated fibers were subsequently preserved, it inhibited macrophage and IL-17+ cell infiltration in PNS, and it significantly reduced circulating pro-inflammatory cytokines. Conclusions FTY720 treatment has beneficial effects on c-EAN, a new animal model mimicking human CIDP. We have shown that FTY720 is an effective immunomodulatory agent, improving the disease course of c-EAN, preserving the myelinated fibers, attenuating the axonal degeneration, and decreasing the number of infiltrated inflammatory cells in peripheral nerves. These data confirm the interest of testing FTY720 or molecules targeting S1P in human peripheral neuropathies.

Background and aims: To develop recommendations for vaccination for coronavirus‐19 (COVID‐19) in patients with inflammatory neuropathies. Methods: Key questions were formulated in order to perform a literature review on the safety and efficacy of vaccines in patients with inflammatory neuropathies. Based on the best evidence and expert opinion, a list of recommendations was formulated to inform decision on vaccination for COVID‐19 in patients with inflammatory neuropathies and increase adherence to vaccination programmes. Results: Recommendations addressing safety and efficacy of vaccination in patients with inflammatory neuropathies were formulated. No data are currently available on the safety and efficacy of COVID‐19 vaccines in patients with inflammatory neuropathies or other immune‐mediated conditions. There is only sparse data on the safety of previous available vaccines in patients with inflammatory neuropathies, but studies on other autoimmune disorders indicate that these are safe and mostly efficacious. Patients with inflammatory neuropathies might be at increased risk for severe illness from COVID‐19. Interpretation: Patients with inflammatory neuropathies should be encouraged to adhere to the vaccination campaign for COVID‐19. These recommendations provide guidance on the management of vaccinations for COVID‐19 in patients with inflammatory neuropathies. More research is needed regarding the safety and efficacy of vaccination in patients with inflammatory neuropathies and other immune conditions. [ABSTRACT FROM AUTHOR]

Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 ( RFC1 ) have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of cases with idiopathic sensory neuropathy. Here, we screened a well-characterized cohort of inflammatory neuropathy patients for RFC1 repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in the pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of the AAAGG and AAAAG repeat units. None of the patients showed biallelic AAGGG expansion of RFC1 , and their carrier frequency for AAGGG was comparable with controls [ n = 27 (5.2%) and n = 23 (4.7%), respectively; P > 0.5]. Data suggest that the pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies nor lead to misdiagnosed cases. Accordingly, routine genetic screening for RFC1 repeat expansion is not indicated in this patient population., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Inflammatory polyradiculoneuropathies are heterogeneous disorders characterized by immune-mediated leukocyte infiltration of peripheral nerves and nerve roots leading to demyelination or axonal degeneration or both. Inflammatory polyradiculoneuropathies can be divided into acute and chronic: Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy and their variants. Despite major advances in immunology and molecular biology have been made in the last years, the pathogenesis of these disorders is not completely understood. This review summarizes the current literature of the clinical features and pathogenic mechanisms of inflammatory polyradiculoneuropathies and focuses on current therapies and new potential treatment for the future. [ABSTRACT FROM AUTHOR]

Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies.Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63).Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies.Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies.

Autoimmunity of the peripheral and central nervous system is an important cause of disease and long-term neurological disability. Autoantibodies can target both intracellular and extracellular neuronal epitopes. Autoantibodies that target cell-surface epitopes infer pathogenicity through several distinct mechanisms, while patients often respond to immunotherapy. However, the underlying pathogenesis of these autoantibodies is yet to be fully understood. Human stem cell–based disease modeling, and the rise of induced pluripotent stem cell technology in particular, has revolutionized the fields of disease modeling and therapeutic screening for neurological disorders. These human disease models offer a unique platform in which to study autoimmunity of the nervous system. Here, we take an in-depth look at the possibilities that these models provide to study neuronal autoantibodies and their underlying pathogenesis. [ABSTRACT FROM AUTHOR]

Der N. vagus wird zunehmend zur Beantwortung wissenschaftlicher aber auch klinischer Fragestellungen mittels Ultraschall untersucht. Dieser Artikel gibt zunächst einen kurzen Überblick über die Anatomie des N. vagus bevor die wichtigsten Indikationen diskutiert werden. Anschließend liegt der Fokus auf der ausführlichen Darstellung der praktischen Ultraschalluntersuchung mit Angabe von Normalwerten. The vagus nerve is increasingly examined by ultrasound addressing both, scientific and clinical questions. This article gives a short overview about the vagal anatomy before discussing the most important indications for the ultrasound examination of the vagus nerve. Subsequently, the focus is laid on the detailed description of the practical aspects of the ultrasound examination. Finally, normal reference values are given. [ABSTRACT FROM AUTHOR]

Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies. Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63). Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies. Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or misfolded proteins, it has not been addressed whether autophagy, a central “clearance” system delivering damaged intracellular components to lysosomes, is affected in CIDP. The focus of the present investigation was therefore to determine if some defects exist in autophagy processes in this setting and if they can be corrected or minimized using an appropriate treatment targeting this survival pathway. Experiments were performed using a rat model mimicking human CIDP, also known as chronic experimental autoimmune neuritis (c-EAN), the disease establishment and development of which was followed at both the clinical and biological levels (indices of disease severity, histopathological alteration, cytokines and antibodies rates). Based on immunofluorescence and western immunoblotting experiments on sciatic nerves and spleen cells from c-EAN rats, we demonstrate that both, macroautophagy and chaperone-mediated autophagy (CMA), are significantly altered in non-neuronal cells of the peripheral nervous system. We show further that a 21-mer synthetic phosphopeptide called P140, known to target CMA and successfully used in pathological settings where CMA markers are overexpressed, considerably ameliorates the clinical and biological course of the disease in c-EAN rats. P140 displayed prophylactic and therapeutic effects, both in terms of disease intensity and chronicity, and preserved sciatic nerves from disease-related damages. Our findings uncover new disrupted molecular pathways in a c-EAN model and provide a proof-of-concept that targeting CMA might represent a promising therapeutic strategy for treating inflammatory neuropathies for which no disease-specific treatment is currently available. [ABSTRACT FROM AUTHOR]

New imaging modalities like high-resolution-ultrasound (HRUS) and MR-Neurography (MRN) are increasingly used for the evaluation of the peripheral nervous system. The increasing knowledge on morphological changes observed in different neuropathies has led to a better understanding of underlying pathophysiological processes. The diagnosis of acquired chronic dysimmune neuropathies (CDN) like chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner Syndrome (LSS) or multifocal motor neuropathy (MMN) can be challenging. The current diagnostic criteria and outcome parameters are mainly based on clinical and electrophysiological parameters. Especially in CDN cases with atypical presentation or during early disease stages, the diagnostic accuracy is low and standardized protocols for the evaluation of disease activity and treatment response are lacking. The establishment of combined diagnostic criteria for CDN including imaging modalities could help to improve the diagnostic accuracy, allow a better differentiation of subtypes and facilitate the follow-up of disease course. The appropriate selection of eligible patients and sensitive monitoring of treatment response is mandatory future in treatment trials. In this article, we briefly summarize the clinical presentations and pathophysiological concepts of different CDN like CIDP, LSS and MMN. Furthermore, this review focuses on the diagnostic value of HRUS/MRN and its potential role for the monitoring of disease activity. [ABSTRACT FROM AUTHOR]

Objective The main objective of this study was to evaluate the correlation between the distribution of brachial plexus magnetic resonance imaging ( MRI) abnormalities and clinical weakness, and to evaluate the value of brachial plexus MRI in predicting disease course and response to treatment in multifocal motor neuropathy ( MMN), Lewis-Sumner syndrome ( LSS) and chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP). Methods Sixty-seven patients with an inflammatory neuropathy diagnosed at our tertiary referral center for neuromuscular diseases had undergone bilateral T2-weighted short tau inversion recovery ( STIR) MRI of the brachial plexus. We obtained clinical follow-up data and scored all MRIs for abnormalities and the symmetry of their distribution. Results Brachial plexus MRI abnormalities were detected in 45% of the patients. An abnormal MRI did not predict disease course in terms of patterns of weakness, sensory disturbances or response to treatment. Within the spectrum of radiological abnormalities, asymmetrical clinical syndromes, MMN and LSS were significantly associated with asymmetrical radiological abnormalities, whereas symmetrical abnormalities predominated in CIDP ( p < .001, phi 0.791). Conclusion T2 STIR brachial plexus MRI abnormalities correspond with the distribution of neurological deficits in inflammatory neuropathies, but do not correlate with specific clinical characteristics, response to treatment or disease course. [ABSTRACT FROM AUTHOR]

Zusammenfassung Der hochauflösende Ultraschall hat in den letzten Jahren zunehmende Bedeutung in der Diagnostik peripherer neurologischer Erkrankungen gewonnen. Mit dem Ultraschall lässt sich ein Großteil der peripheren Nerven der oberen und unteren Extremitäten verlässlich darstellen. Der Ultraschall stellt dabei eine komplementäre Methode zur Elektrophysiologie dar, mit der wichtige morphologische Informationen pathologischer Veränderungen der Nerven selbst wie auch deren Umgebungsgewebe erhoben werden können. Sonographisch lässt sich häufig der Schädigungsort präzise lokalisieren und ätiologische Zusatzinformationen erhalten. Die wichtigsten Indikationen des Nervenultraschalls stellen die Diagnostik von Engpasssyndromen, traumatischen Nervenverletzungen, Raumforderungen am peripheren Nerven und (entzündliche) Polyneuropathien dar. Summary High-resolution ultrasound has gained a growing importance in the diagnostic work-up of peripheral nerve disorders in recent times. By means of ultrasound most peripheral nerves of the upper and lower extremities can reliably be visualized. Ultrasound is considered as a complementary method to nerve conduction studies that provides additional information on morphologic changes of the nerve's structure and of its surrounding tissue. It further enables more precise localization of nerval lesion as well as other information about the underlying etiology. The most important indications for ultrasonography are entrapment syndromes like the carpal or cubital tunnel syndrome, traumatic nerve injuries, benign nerve sheath tumors and inflammatory neuropathies. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context.We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. [ABSTRACT FROM AUTHOR]

The 'ability to walk' is considered a benchmark for good clinical recovery and prognosis, particularly in patients with Guillain-Barré syndrome ( GBS) and chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP). However, it has never been determined whether being 'able to walk' represents general functionality. The purpose of this study was to examine whether the ability to walk outside independently reflects general functional improvement in patients with GBS, CIDP, and gammopathy-related neuropathy ( MGUSP). A total of 137 patients with newly diagnosed (or relapsing) GBS (55), CIDP (59), and MGUSP (23) were serially examined (1-year). Predefined arbitrary cut-offs (so-called patients' Functional-Acceptable-Clinical-Thresholds [ FACTs]) were taken at the 50th, 75th, and 90th percentile of the Inflammatory-Rasch-built-Overall-Disability-Scale (I- RODS©). We determined the proportion of patients able to walk outside independently that reached the postulated cut-offs. A mean total of 85%, 39%, and 12% of all patients able to walk reached 50th, 75th, and 90th percentile thresholds, respectively. These findings were not neuropathy type related. Our findings show that assessing only one construct of functionality (e.g., walking ability) does not reflect the full scope of daily/social functional deficits perceived by patients. The ability to walk shows a patient is doing better, but not necessarily doing well. The I- RODS© bypasses these limitations. [ABSTRACT FROM AUTHOR]

Background: Hyperechogenicity of the substantia nigra was recently reported in patients with sporadic ALS with a frequency similar to PD. Data on the diagnostic utility compared to key differential diagnoses of ALS do not exist yet. Methods: We prospectively enrolled 43 patients with ALS, 29 with myasthenia gravis, 25 patients with inflammatory neuropathy, and 13 with cervical canal stenosis. All patients were examined by a blinded investigator using transcranial B-mode sonography planimetrically measuring hyperechogenic areas of the midbrain representing the substantia nigra. Results: Mean midbrain hyperechogenic area was increased in ALS compared to non-ALS differentials. ROC analysis revealed only small area under the curve for detecting ALS (AUC: 0.669 [95%CI: 0.56-0.78]; p = 0.006). Highest Youden index was observed for area size of <0.14 cm² (Youden index: 0.28). Using this cut-off score and that generated from normative data of healthy controls, area size measurements provided a sensitivity of only 46-58% and specificity of 69-83% for detecting ALS. No correlations of hyperechogenic area sizes in ALS patients were found to age, gender, ALS subtype (bulbar versus spinal form), disease duration or ALS-FRS-R score. Conclusions: Midbrain hyperechogenicity is reproducibly found in ALS patients, but its diagnostic value for discriminating ALS from its key differentials is limited. [ABSTRACT FROM AUTHOR]

Most inflammatory neuropathies, both acute and chronic, probably result from an immune attack against antigens of the peripheral nervous system. Specific antibodies in serum that react with the peripheral nervous system have been described in a number of inflammatory neuropathies. We review the pathophysiological significance of auto-antibodies and discuss their use for the diagnosis of patients with peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor alpha (TNFα) is a peptide that is derived from T lymphocytes and macrophages and is used as a marker of activated cellular immune responses. TNFα was measured in paired sera and cerebrospinal fluid (CSF) from 30 patients with multiple sclerosis (MS) with worsening disability, 54 patients with other neurological diseases, and 20 normal subjects. A sensitive enzyme-linked immunosorbent assay was used to determine the TNFα levels. We found significantly elevated serum and CSF levels in 12 (40%) and 6 (20%) MS patients, respectively, compared with healthy controls ( P<0.007 and P<0.05). Among the 18 patients with neuropathy, we also found high serum and CSF TNFα values in 3 (17%) and 5 (28%) patients, respectively ( P<0.04 and P<0.002). Our study shows that TNFα is probably involved in the pathogenetic mechanisms of MS and other inflammatory neurological diseases. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune-mediated inflammatory disease of the peripheral nervous system characterized by a response directed against certain myelin proteins and for which therapies are limited. Previous studies have suggested a beneficial role of FTY720, a sphingosine 1-phosphate (S1P) receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes, in the treatment of experimental autoimmune neuritis (EAN). Therefore, we investigated whether FTY720 is also beneficial in chronic experimental autoimmune neuritis (c-EAN), a recently developed rat model mimicking human CIDP.Methods: c-EAN was induced in Lewis rats by immunization with S-palm P0(180-199) peptide. Rats were treated with FTY720 (1 mg/kg) or vehicle intraperitoneally once daily from the onset of clinical signs for 18 days; clinical signs were assessed daily until 60 days post-immunization (dpi). Electrophysiological and histological features were examined at different time points. We also evaluated the serum levels of different pro- and anti-inflammatory cytokines by ELISA or flow cytometry at 18, 40, and 60 dpi.Results: Our data demonstrate that FTY720 decreased the severity and abolished the chronicity of the disease in c-EAN rats. Therapeutic FTY720 treatment reversed electrophysiological and histological anomalies, suggesting that myelinated fibers were subsequently preserved, it inhibited macrophage and IL-17+ cell infiltration in PNS, and it significantly reduced circulating pro-inflammatory cytokines.Conclusions: FTY720 treatment has beneficial effects on c-EAN, a new animal model mimicking human CIDP. We have shown that FTY720 is an effective immunomodulatory agent, improving the disease course of c-EAN, preserving the myelinated fibers, attenuating the axonal degeneration, and decreasing the number of infiltrated inflammatory cells in peripheral nerves. These data confirm the interest of testing FTY720 or molecules targeting S1P in human peripheral neuropathies. [ABSTRACT FROM AUTHOR]