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Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2-4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12-15 L in four to five exchanges over 1-2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available literature and additional discussions, we provide flow charts to assist making clinical decisions on diagnosis, treatment and the need for intensive care unit admission., (© 2023 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

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., (© 2023 Peripheral Nerve Society.)

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point)., (© 2021 European Academy of Neurology and Peripheral Nerve Society.)

We describe the distinctive features (with images and video) of a case of chronic inflammatory demyelinating polyneuropathy (CIDP) with giant nerves. The main clinical findings were insidious onset, gait ataxia and sensory symptoms. Electrodiagnostic studies showed very slow nerve conduction velocities, multiple conduction blocks, distal CMAP duration increase and absence of F-waves. The protein level in the cerebrospinal fluid was very high. Nerve ultrasound showed swelling of all peripheral nerves outside entrapment sites, with significant variability within different segments of the same nerve; nerves were massively enlarged (up to 10-fold normal values). Brain MRI showed hypertrophic cranial nerves, with gadolinium-enhancement. Spinal MRI showed hypertrophy of spinal roots and cauda equine, with gadolinium enhancement. Genetic test (PMP22 duplication/deletion, Whole Exome Sequencing panel for neuropathies) resulted negative. The patient had a relapsing-remitting course and responded to immunoglobulin treatment. In CIDP with hypertrophic nerves, there is discrepancy between severe nerve hypertrophy and mild clinical symptoms. Nerve enlargement seems inversely related to nerve conduction velocity and directly correlated with disease duration, but not associated with disease severity., (© 2021 Peripheral Nerve Society.)

Acute inflammatory demyelinating polyneuropathy (AIDP) and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) are conditions presenting overlapping clinical features during early stages (first 4 weeks), although the latter may progress after 8 weeks. The aim of this study was to identify predictive factors contributing to their differential diagnosis. Clinical records of adult patients with AIDP or A-CIDP diagnosed at our institution between January 2006 and July 2017 were retrospectively reviewed. Demographic characteristics, clinical manifestations, cerebrospinal-fluid (CSF) findings, treatment and clinical evolution were analyzed. Nerve conduction studies were performed in all patients with at least 12 months follow-up. A total of 91 patients were included (AIDP, n = 77; A-CIDP, n = 14). The median age was 55.5 years in patients with A-CIDP vs 43 years in AIDP (P = .07). The history of diabetes mellitus was more frequent in A-CIDP (29% vs 8%, P = .04). No significant differences between groups were observed with respect to: human immunodeficiency virus (HIV) status, presence of auto-immune disorder or oncologic disease. Cranial, motor and autonomic nerve involvement rates were similar in both groups. Patients in the A-CIDP group showed higher frequency of proprioceptive disturbances (83% vs 28%; P < .001), sensory ataxia (46% vs 16%; P = .01), and the use of combined immunotherapy with corticoids (29% vs 3%; P = .005). There were no significant differences in CSF findings, intensive care unit (ICU) admission, or mortality rates. During the first 8 weeks both entities are practically indistinguishable. Alterations in proprioception could suggest A-CIDP. Searching for markers that allow early differentiation could favor the onset of corticotherapy without delay., (© 2018 Peripheral Nerve Society.)

Despite the well-recognized importance of immunoglobulin therapy individualization during the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), the pathway to best achieve optimization is unknown. There are many pharmacokinetic and immunobiologic variables that can potentially influence the appropriateness of any individual therapy. Although identification of specific autoantibodies and their targets has only been accomplished in a minority of patients with CIDP, already the diagnostic and treatment implications of specific autoantibody detection are being realized. Individual variability in IgG pharmacokinetic properties including IgG catabolic rates and distribution, as well as the IgG level necessary for disease control also require consideration during the optimization process. For optimization to be successful there must be a measure of treatment response that has a clinically meaningful interpretation. There are currently available well-defined and validated clinical assessment tools and outcome measures that are well suited for this purpose. While there remains much to learn on how best to manipulate immunopathology and immunoglobulin pharmacokinetics in the most favorable way, there currently exists an understanding of these principles to a degree sufficient to begin to develop rational and evidence-based treatment optimization strategies., (© 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.)

There is as yet no consensus for considering pure acute sensory ataxic neuropathy (ASAN) as a variant of Guillain-Barré syndrome (GBS). Reactivity against gangliosides sharing disialosyl epitopes has been reported in these patients. The aim of this study was to determine the spectrum of reactivity against gangliosides in ASAN and to define the clinical pattern. From our database we identified patients with suspicion of ASAN. We defined ASAN as the presence of ataxia of peripheral origin with loss of proprioception, and areflexia, absence of ophthalmoplegia and no or minimal muscle weakness. Patients who met these criteria were retrospectively reviewed for their spectrum of reactivity against gangliosides and clinical features. We identified 12 patients fulfilling pre-defined criteria for ASAN. Reactivity against gangliosides containing disialosyl epitopes was present in seven patients. Concomitant reactivity against other gangliosides was present in 6/7 patients. All patients presented good prognosis and an antecedent illness was present in nine. Our results support the previously described clinico-immunological association between ASAN and disialosyl specificity, and widen the spectrum of reactivity against gangliosides. The acute presentation with a monophasic course, and good prognosis in all cases, together with transient immunoglobulin G antiganglioside antibodies and infectious antecedent in 7/12 patients support the inclusion of ASAN as a GBS variant., (© 2012 Peripheral Nerve Society.)