[Peripheral neuroimmunological diseases - Neuropathological insights and clinical perspectives]. / Periphere neuroimmunologische Erkrankungen ­ neuropathologische Einsichten und klinische Perspektiven.

This article deals with peripheral neuroimmunological diseases and briefly outlines the currently most important aspects and treatment developments. Idiopathic inflammatory myopathies have different mechanisms of development, manifestations and prognoses. New classification systems and more specific treatment concepts have been developed. The IIMs include different subgroups. These entities can have specific autoantibodies. Diagnostically, a muscle biopsy is generally desirable for a precise diagnosis and is essential in unclear cases. Primary systemic vasculitides can be divided into different groups based on the predominant pattern of involvement, while secondary vasculitides and single organ vasculitides are also differentiated. Vasculitic myopathy cannot be equated with myositis and a reliable distinction is currently only possible by a muscle biopsy. Treatment concepts should be developed on an interdisciplinary basis. Chronic inflammatory demyelinating polyneuropathy is the most frequent immune-mediated neuropathy and is characterized by a predominant demyelination of the motor and sensory nerves. The disease course runs in phases or is progressive and leads to significant disability and reduction in quality of life, despite current standard treatment. Novel treatment approaches are currently undergoing clinical trials. Myasthenia gravis, with the leading symptom of exercise-induced muscle weakness, is caused by autoantibodies against structures of the neuromuscular endplate. Autoantibody testing is the most important pillar in the diagnosis and is now also increasingly guiding treatment decisions. Overall, peripheral neuroimmunological diseases represent a heterogeneous group. Increasing knowledge of the pathophysiology is the key to numerous developments in diagnostics and treatment, which could lead to far-reaching practical changes in the future.

[Immune-mediated neuropathies: pathophysiology and management].

Immune-mediated neuropathies (IMN) are a heterogenous group of disorders affecting the peripheral nervous system, due to dysregulation of the immune system. It mainly includes Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy and so on. Most of these diseases can be clinically improved by appropriate immunotherapy, but some patients still have unsatisfactory results. Therefore, studying the pathophysiology of the occurrence and development of diseases can reveal the nature of diseases and provide a theoretical basis for the prevention, diagnosis and treatment of diseases. In this paper, the pathophysiological mechanism of various IMNs is described in detail, with emphasis on immunological mechanism, and the progress of diagnosis and treatment of various IMNs is briefly introduced.

Usefulness of somatosensory evoked potentials for monitoring the clinical course of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Somatosensory evoked potentials (SSEPs) are described as a supportive tool to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, there is a lack of studies determining the effectiveness of SSEPs in monitoring the clinical course of individuals with this condition. The aims of this study are to evaluate the utility of SSEPs in monitoring patients with CIDP and to assess their association with clinical outcomes following immunomodulatory therapy. METHODS: This was a single-center retrospective observational study that included patients who met European Federation of Neurological Societies and Peripheral Nerve Society criteria for CIDP between 2018 and 2023. SSEPs were performed at diagnosis and during follow-up after the start of immunomodulatory treatment. Fisher's exact test was employed to assess the association between clinical improvement and SSEP improvement. RESULTS: Eighteen patients were included in the study. Ten patients had a typical CIDP pattern and 11 were male. In 17, SSEPs were abnormal prior to the start of immunomodulatory treatment. In patients who showed clinical improvement with immunomodulatory therapy, we observed that 15/17 had partial or complete improvement in SSEPs. Patients who showed no clinical improvement with first-line treatment exhibited worsening SSEPs. There was a significant association between clinical and SSEPs improvement (p = 0.009). DISCUSSION: We observed a positive association between improvement in SSEPs and clinical improvement in patients with CIDP. Our data suggest that SSEPs may be useful for monitoring the clinical course of patients with CIDP, but additional, larger studies are needed.

The difference in nerve ultrasound and motor nerve conduction studies between autoimmune nodopathy and chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: Nerve enlargement has been described in autoimmune nodopathy and chronic inflammatory demyelinating polyneuropathy (CIDP). However, comparisons of the distribution of enlargement between autoimmune nodopathy and CIDP have not been well characterized. To fill this gap, we explored differences in the ultrasonographic and electrophysiological features between autoimmune nodopathy and CIDP. METHODS: Between March 2015 and June 2023, patients fulfilling diagnostic criteria for CIDP were enrolled; among them, those with positive antibodies against nodal-paranodal cell-adhesion molecules were distinguished as autoimmune nodopathy. Nerve ultrasound and nerve conduction studies (NCS) were performed. RESULTS: Overall, 114 CIDP patients and 13 patients with autoimmune nodopathy were recruited. Cross-sectional areas (CSA) at all sites were larger in patients with CIDP and autoimmune nodopathy than in healthy controls. CSAs at the roots and trunks of the brachial plexus were significantly larger in patients with anti-neurofascin-155 (NF155), anti-contactin-1 (CNTN1), and anti-contactin-associated protein 1 (CASPR1) antibodies than in CIDP patients. The patients with anti-NF186 antibody did not have enlargement in the brachial plexus. NCS showed more frequent probable conduction block at Erb's point in autoimmune nodopathy than in CIDP (61.9% vs. 36.6% for median nerve, 52.4% vs. 39.5% for ulnar nerve). Markedly prolonged distal motor latencies were also present in autoimmune nodopathy. DISCUSSION: Patients with autoimmune nodopathies had distinct distributions of peripheral nerve enlargement revealed by ultrasound, as well as distinct NCS patterns, which were different from CIDP. This suggests the potential utility of nerve ultrasound and NCS to supplement clinical characteristics for distinguishing nodopathies from CIDP.

[A borderline case between multifocal motor neuropathy and motor chronic inflammatory demyelinating polyneuropathy revealed by the magnetic fatigue test].

A 26-year-old woman presented with a seven-month history of weakness in her left upper limb, progressing to difficulty lifting her arms within a few weeks. Her symptoms progressed with fluctuations. For the past three months, she has been unable to stand due to weakness in her proximal lower limbs. Nerve conduction studies did not show any definite conduction block or abnormal sensory conduction, but motor conduction studies showed a slight prolongation of the terminal latency and a decrease in the frequency of the F-wave. A magnetic fatigue test indicated a proximal conduction block. Her symptoms were rapidly resolved with intravenous immunoglobulin treatment, leading to a diagnosis of chronic immune-mediated neuropathy, met both criteria for multifocal motor neuropathy (MMN) and motor chronic inflammatory demyelinating polyneuropathy (CIDP). Our case highlights the utility of the magnetic fatigue test in detecting conduction blocks and its role in differentiating between MMN and motor CIDP.

Treatment response in patients with clinical and supportive laboratory features of chronic inflammatory demyelinating polyneuropathy without demyelinative findings on nerve conduction studies: A retrospective study.

INTRODUCTION/AIMS: Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. METHODS: Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). RESULTS: Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. DISCUSSION: A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.

Treatment response amplitude and timing in chronic inflammatory demyelinating polyneuropathy with routine care: Study of a UK cohort.

BACKGROUND AND PURPOSE: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. METHODS: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment-response category" (CT-RC), based on achieved endpoints. Determinants of the CT-RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. RESULTS: The CT-RC demonstrated high concurrent validity with current outcome measures. Thirty-six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT-RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1-36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. CONCLUSIONS: CT-RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician- and patient-related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP.

The multiple roles of nerve biopsy in the diagnosis and prognosis of suspected immune neuropathies.

INTRODUCTION: The value of a sural nerve biopsy for the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is controversial. Evidence-based recommendations for its implementation are lacking. We investigated factors leading to biopsy and analyzed biopsy outcomes and consequences, assessed the predictability of biopsy outcomes through clinical parameters to avoid unnecessary biopsies, and compared results with electrophysiological and clinical severity to determine their prognostic value. METHODS: 190 sural nerve biopsies were analyzed in two cohorts. One consisted of 163 biopsies and the second of 72 biopsies from the prospective Immune-mediated Neuropathies Biomaterial and Data registry (INHIBIT). Both have an intersection of 45 patients. 75 data sets from patients without biopsy were used. Analysis of nerve conduction studies, treatment, overall disability sum score (ODSS), biopsy outcomes, and diagnosis was performed. RESULTS: 51% of biopsied patients received the diagnosis CIDP (77% fulfilled EFNS/PNS criteria), 21% were not CIDP typical, and 27% were unspecific. Biopsied patients responded less frequently to immunotherapies at time of biopsy than non-biopsied patients (p = 0.003). Immunotherapy was initiated more frequently after biopsy (p < 0.001) and more often with intravenous immunoglobulins (p < 0.0001). 76% of all biopsied patients met the electrophysiological criteria for CIDP. Sensory nerve action potential amplitudes of 0 µV still provide 73% of histological diagnostic value. Histologic signs of degeneration predicted ODSS worsening after 1 year (p = 0.028) but disease severity did not correlate with histological damage severity. DISCUSSION: The main indication for nerve biopsy was the treatment of refractory cases of autoimmune neuropathies with the therapeutic consequence of treatment initiation or escalation. Sural biopsy also provided prognostic information. Even with extinguished sural SNAP, the biopsy can still have diagnostic value.

Whole-body magnetic resonance neurography in patients with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients. METHODS: Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment. RESULTS: We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy. DISCUSSION: Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months.

[CIDP Variants].

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous syndrome that has several variants. Although they share macrophage-associated demyelination, clinical, neurophysiological, and pathological investigations have demonstrated that each subtype has a different pathophysiology. Multifocal CIDP exhibits a chronic course with asymmetrical symptoms. Its neurophysiological significance involves multifocal demyelination at intermediate nerve sites. Distal CIDP has a prolonged chronic course, presenting sensory and motor symptoms in a length-dependent manner. Furthermore, it frequently coexists with IgG M proteinemia or other hematologic disorders. Motor CIDP displays symmetric muscle weakness similar to typical CIDP but lacks sensory involvement. Often, motor CIDP is associated with malignancy or inflammatory diseases. Although acute deterioration after corticosteroid therapy in patients with motor CIDP is well-known, the available evidence to support this is limited.

Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review.

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.

iMAX: A new tool for assessment of motor axon excitability. A multicenter prospective study.

OBJECTIVE: This study was undertaken to establish by a multicentric approach the reliability of a new technique evaluating motor axon excitability. METHODS: The minimal threshold, the lowest stimulus intensity allowing a maximal response by 1 mA increments (iUP) and then by 0.1 mA adjustments (iMAX) were prospectively derived from three nerves (median, ulnar, fibular) in four university centers (Liège, Marseille, Fraiture, Nice). iMAX procedure was applied in 28 healthy volunteers (twice) and 32 patients with Charcot-Marie-Tooth (CMT1a), chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré syndrome (SGB) or axonal neuropathy. RESULTS: Healthy volunteers results were not significantly different between centers. Correlation coefficients between test and retest were moderate (> 0.5). Upper limits of normal were established using the 95th percentile. Comparison of volunteers and patient groups indicated significant increases in iMAX parameters especially for the CMT1a and CIDP groups. In CMT1a, iMAX abnormalities were homogeneous at the three stimulation sites, which was not the case for CIDP. CONCLUSIONS: The iMAX procedure is reliable and allows the monitoring of motor axon excitability disorders. SIGNIFICANCE: The iMAX technique should prove useful to monitor motor axonal excitability in routine clinical practice as it is a fast, non-invasive procedure, easily applicable without specific software or devices.

CNS Involvement in Chronic Inflammatory Demyelinating Polyneuropathy: Subtle Retinal Changes in Optical Coherence Tomography.

BACKGROUND AND OBJECTIVES: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease primarily affecting the peripheral nervous system. However, several noncontrolled studies have suggested concomitant inflammatory CNS demyelination similar to multiple sclerosis. The aim of this study was to investigate an involvement of the visual pathway in patients with CIDP. METHODS: In this prospective cross-sectional study, we used high-resolution spectral-domain optical coherence tomography to compare the thickness of the peripapillary retinal nerve fiber layer and the deeper macular retinal layers as well as the total macular volume (TMV) in 22 patients with CIDP and 22 age-matched and sex-matched healthy control (HC) individuals. Retinal layers were semiautomatically segmented by the provided software and were correlated with clinical measures and nerve conduction studies. RESULTS: In patients with CIDP compared with healthy age-matched and sex-matched controls, we found slight but significant volume reductions of the ganglion cell/inner plexiform layer complex (CIDP 1.86 vs HC 1.95 mm3, p = 0.015), the retinal pigment epithelium (CIDP 0.38 vs HC 0.40 mm3, p = 0.02), and the TMV (CIDP 8.48 vs HC 8.75 mm3, p = 0.018). The ganglion cell layer volume and motor nerve conduction velocity were positively associated (B = 0.002, p = 0.02). DISCUSSION: Our data reveal subtle retinal neurodegeneration in patients with CIDP, providing evidence for visual pathway involvement, detectable by OCT. The results need corroboration in independent, larger cohorts.

Corneal inflammatory cell infiltration predicts disease activity in chronic inflammatory demyelinating polyneuropathy.

The assessment of disease activity is fundamental in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Previous studies with small patient numbers found an increase of corneal immune cell infiltrates as a potential marker of inflammation in patients with CIDP. However, its clinical relevance remained unclear. The present study aimed to determine whether the amount of corneal inflammatory cells (CIC) measured by corneal confocal microscopy (CCM) detects disease activity in CIDP. CIC were measured in 142 CCM-investigations of 97 CIDP-patients. Data on clinical disease activity, disability (INCAT-ODSS) and need for therapy escalation at the timepoint of CCM, 3 and 6 months later were analyzed depending CIC-count. Pathological spontaneous activity during electromyography was examined as another possible biomarker for disease activity in comparison to CIC-count. An increased CIC-count at baseline was found in patients with clinical disease activity and disability progression in the following 3-6 months. An increase to more than 25 CIC/mm2 had a sensitivity of 0.73 and a specificity of 0.71 to detect clinical disease activity and a sensitivity of 0.77 and a specificity of 0.64 to detect disability progression (increasing INCAT-ODSS) in the following 6 months. An increase to more than 50 CIC/mm2 had a sensitivity of about 0.51 and a specificity of 0.91 to detect clinical disease activity and a sensitivity of 0.53 and a specificity of 0.80 to detect disability progression. CIC count is a non-invasive biomarker for the detection of disease activity in the following 6 months in CIDP.

Electrophysiological predictors of response to subcutaneous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To assess axonal function prior to subcutaneous immunoglobulin (SCIG) therapy or placebo in relation to relapse in chronic inflammatory demyelinating polyneuropathy (CIDP) to determine whether axonal damage can predict therapy response. METHODS: Relapse rates in patients from the Polyneuropathy and Treatment with Hizentra (PATH) study, where patients were treated with placebo or SCIG (IgPro20), were analyzed by baseline (post-intravenous immunoglobulin stabilization) axonal damage (≤1 mV peroneal compound muscle action potential) status. RESULTS: In patients with non-axonal damage, relapses were significantly higher with placebo (73.0%) than IgPro20 (0.2 g/kg: 39.1%, 0.4 g/kg: 19.2%). In patients with axonal damage, IgPro20 had no effect on relapse (placebo: 25.0%, IgPro20: 0.2 g/kg: 30.0%, 0.4 g/kg: 19.4%). Patients with axonal damage relapsed significantly less on placebo versus non-axonal damage, but they also demonstrated higher baseline disability. CONCLUSION: Axonal damage may correspond to relapse upon treatment withdrawal; patients with axonal damage relapse less, possibly reflecting poor response to immunoglobulin therapy, while non-axonal damage patients may experience more relapse, perhaps indicating better treatment response. SIGNIFICANCE: In CIDP patients with axonal loss, immunoglobulin therapy may not be as effective. Assessing axonal damage could help guide therapy, with immunoglobulins ideally used before substantial axonal damage arises.

Evaluation of the EFNS/PNS diagnostic criteria in a cohort of CIDP patients.

OBJECTIVE: To evaluate the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) in a cohort of patients diagnosed and treated for CIDP in a tertiary university hospital. METHODS: In a monocentric retrospective study of 203 CIDP patients, diagnosed according to expert opinion, we evaluated the EFNS/PNS diagnostic criteria. Clinical course and nerve conduction studies (NCS) over 1 year from first referral were studied. Secondarily, we compared the clinical and paraclinical characteristics, including nerve ultrasound, of patients who failed with those who fulfilled the criteria in order to identify clinically relevant differences. RESULTS: At 1 year, 182 (89.7%) patients fulfilled the criteria (156/76.9% definite, 22/10.8% probable, and 4/2% possible). Twenty-one (10.3%) patients did not because the electrodiagnostic criteria remained negative. These still showed signs of demyelination but did not reach the cut-off values. They also presented typical, albeit less pronounced, multifocal nerve enlargement in ultrasonography. Mean disability at presentation and 1 year after was significantly lower. Most importantly, a relevant proportion of these patients also responded to therapy (6/21 = 28.6% vs. 82/182 = 45.3% of those fulfilling the criteria). INTERPRETATION: CIDP diagnosis could be established for 89.7% of patients over the course of 1 year using EFNS/PNS criteria. The remaining patients (10.3%) presented with milder disability, less accentuated demyelination, but otherwise similar characteristics and still considerable probability of treatment response. Failure to fulfill diagnostic criteria should not automatically preclude treatment. Nerve ultrasound should be considered as a complementary diagnostic tool to detect signs of inflammation in CIDP.

Recovery of foot drop in chronic inflammatory demyelinating polyneuropathy (CIDP).

INTRODUCTION/AIMS: Foot drop is common in chronic inflammatory demyelinating polyneuropathy (CIDP), but its prognosis is uncertain. METHODS: CIDP patients with less than anti-gravity strength (<3/5 power) of ankle dorsiflexion (ADF) on Medical Research Council manual muscle testing on presentation at our center were identified by retrospective review. After initiation of standard treatment, ADF power was serially tabulated, and predictors of recovery were determined. RESULTS: Of the 27 identified patients, ADF power at presentation was <3/5 in 48/54 legs. At 1 y after treatment, ADF power improved to >/= 3/5 in 17/27 patients in one (N = 6) or both (N = 11) legs. On multi-variate analysis, predictors of recovery of ADF power were tibialis anterior compound muscle action potential amplitude at presentation, shorter disease duration, and female gender. DISCUSSION: Foot drop improves to anti-gravity power in most treated CIDP patients depending in part on the severity of fibular motor axon loss at onset of treatment.

Expanding the Spectrum of Chronic Immune Sensory Polyradiculopathy: CISP-Plus.

OBJECTIVE: Sensory loss with normal nerve conduction studies (NCS) from focal sensory root inflammatory demyelination is characteristic of chronic immune sensory polyradiculopathy (CISP). However, nonpure cases involving motor and distal sensory nerves exist (CISP-plus). We hypothesize that CISP-plus and CISP are fundamentally part of the same syndrome through comparison of clinical, neurophysiologic, and pathologic features. METHODS: CISP-plus (primary dorsal root with lesser motor and sensory nerve involvement) and CISP cases were retrospectively analyzed (1986-2019). RESULTS: We identified 44 CISP-plus and 28 CISP cases (n = 72) with 86% (38/44) of patients with CISP-plus and 79% (22/28) of patients with CISP experiencing imbalance. On examination, large fiber sensory loss was present in 98% (43/44) of patients with CISP-plus and 96% (27/28) of patients with CISP. Gait ataxia was evident in 93% (41/44) of patients with CISP-plus and 79% (22/28) of patients with CISP. Mild distal weakness was common in CISP-plus (75%, 33/44). NCS showed mild abnormalities in all patients with CISP-plus and were normal (by definition) in all patients with CISP. Elevated CSF protein, slowing of somatosensory evoked potentials, and MRI root enhancement occurred in most CISP-plus and CISP cases. Eleven CISP-plus nerve biopsies showed loss of large myelinated fibers and onion-bulb formations, most prominent in rootlet biopsies. Immunotherapy resulted in marked improvement of gait ataxia in 84% (27/32) of patients with CISP-plus and 93% (13/14) of patients with CISP with return to normal neurologic examination in half (25/46). CONCLUSION: The recognition of CISP-plus expands the spectrum of CIDP by combining CISP-plus (predominant sensory polyradiculopathy with mild motor and sensory nerve involvement) with pure CISP (focal sensory polyradiculopathy) together as proximal sensory CIDP.

Patients who meet electrodiagnostic criteria for CIDP rarely present with a sensory predominant DSP phenotype.

INTRODUCTION: It is unknown how often patients with electrodiagnostic evidence of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a potentially treatable condition, present with a distal symmetric polyneuropathy (DSP) phenotype. METHODS: We reviewed the records of patients who presented to our electrodiagnostic laboratory between January 1, 2011, to December 31, 2019, and fulfilled electrodiagnostic criteria for CIDP to identify those who presented with a sensory predominant DSP phenotype. RESULTS: One hundred sixty-two patients had a chronic acquired demyelinating neuropathy, of whom 138 met criteria for typical or atypical CIDP. Nine of these patients presented with a sensory predominant DSP phenotype, among whom six were eventually diagnosed with distal acquired demyelinating symmetric (DADS) neuropathy; one with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome; and two with idiopathic DSP. The prevalence of acquired chronic demyelinating neuropathies among all patients presenting with a DSP phenotype was estimated to be 0.34%. DISCUSSION: Patients who meet electrodiagnostic criteria for CIDP rarely present with a sensory predominant DSP phenotype, and electrodiagnostic testing rarely identifies treatable demyelinating neuropathies in patients who present with a DSP phenotype.