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.

Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson's disease.

The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.

[Public health situation of CIDP patients in nine German centers-neuritis network Germany]. / Versorgungssituation von CIDP-Patienten in neun deutschen Zentren des Neuritis Netzes.

BACKGROUND: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases. OBJECTIVES: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz". MATERIAL AND METHODS: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data. RESULTS: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients. CONCLUSIONS: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz.

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis.

Proteasome inhibition with bortezomib has been reported to exert an immunomodulatory action in chronic autoimmune neuropathies. However, bortezomib used for the treatment of multiple myeloma induces a painful toxic polyneuropathy at a higher concentration. Therefore, we addressed this controversial effect and evaluated the neurotoxic and immunomodulatory mode of action of bortezomib in experimental autoimmune neuritis. Bortezomib-induced neuropathy was investigated in Lewis rats using the von Frey hair test, electrophysiological, qPCR and histological analyses of the sciatic nerve as well as dorsal root ganglia outgrowth studies. The immunomodulatory potential of bortezomib was characterized in Lewis rats after experimental autoimmune neuritis induction with P253-78 peptide. Clinical, electrophysiological, histological evaluation, von Frey hair test, flow cytometric and mRNA analyses were used to unravel the underlying mechanisms. We defined the toxic concentration of 0.2 mg/kg bortezomib applied intraperitoneally at Days 0, 4, 8 and 12. This dosage induces a painful toxic neuropathy but preserves axonal regeneration in vitro. Bortezomib at a concentration of 0.05 mg/kg significantly ameliorated experimental autoimmune neuritis symptoms, improved experimental autoimmune neuritis-induced hyperalgesia and nerve conduction studies, and reduced immune cell infiltration. Furthermore, proteasome inhibition induced a transcriptional downregulation of Nfkb in the sciatic nerve, while its inhibitor Ikba (also known as Nfkbia) was upregulated. Histological analyses of bone marrow tissue revealed a compensatory increase of CD138+ plasma cells. Our data suggest that low dose bortezomib (0.05 mg/kg intraperitoneally) has an immunomodulatory effect in the context of experimental autoimmune neuritis through proteasome inhibition and downregulation of nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFKB). Higher bortezomib concentrations (0.2 mg/kg intraperitoneally) induce sensory neuropathy; however, the regeneration potential remains unaffected. Our data empathizes that bortezomib may serve as an attractive treatment option for inflammatory neuropathies in lower concentrations.

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.

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.

Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study.

BACKGROUND: Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce. METHODS: We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS). RESULTS: A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p = 0.04, χ 2-test, n = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p = 0.02, t-test, n = 48). Patients with Lewis-Sumner syndrome (n = 9) and autoantibody mediated neuropathies (n = 13) had excellent response rates after treatment with RTX (90-100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ. CONCLUSION: Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.

Nerve Ultrasound Distinguishes Non-Inflammatory Axonal Polyneuropathy From Inflammatory Polyneuropathy With Secondary Axonal Damage.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) may have a similar clinical and electrophysiological presentation to non-inflammatory axonal polyneuropathies (NIAPs) when secondary axonal damage occurs. We aimed to investigate if nerve ultrasound can help to differentiate CIDP with additional secondary axonal damage from NIAP. METHODS: In a retrospective analysis, the cross-sectional area (CSA) of the peripheral nerves measured by ultrasound at six suitable nerve sites was compared in 95 patients with CIDP and 82 patients with NIAP. We developed the adjusted Bochum ultrasound score (aBUS) ranging from 0 to 6 resulting from the number of sites with enlarged CSA (median, ulnar, radial, and sural nerve). RESULTS: The mean CSA of patients with CIDP was enlarged at all six nerve sites compared with the mean CSA of patients with NIAP. A total of 21 patients with CIDP did not meet 2010 electrophysiological diagnostic criteria (European Academy of Neurology/Peripheral Nerve Society Guideline, EFNS/PNS criteria) for CIDP at examination timepoint but only in further follow-up, while 25 patients with NIAP fulfilled electrophysiological EFNS/PNS criteria for CIDP as "possible" or "probable" CIDP. To increase diagnostic power, we included aBUS measured by ultrasound in patients classified as "possible" or "probable" resulting in an improved specificity of 94% and a sensitivity of 59%, compared to a specificity of the EFNS/PNS criteria alone of 60% and sensitivity of 78%. CONCLUSION: Using nerve ultrasound and the aBUS as a complementary method to distinguish CIDP from NIAP in case of secondary axonal damage can facilitate the diagnosis of CIDP.

New Approaches to Critical Illness Polyneuromyopathy: High-Resolution Neuromuscular Ultrasound Characteristics and Cytokine Profiling.

BACKGROUND: Diagnosis of intensive care unit acquired weakness (ICUAW) is challenging. Pathogenesis of underlying critical illness polyneuromyopathy (CIPNM) remains incompletely understood. This exploratory study investigated whether longitudinal neuromuscular ultrasound examinations and cytokine analyses in correlation to classical clinical and electrophysiological assessment contribute to the understanding of CIPNM. METHODS: Intensive care unit patients were examined every 7 days until discharge from hospital. Clinical status, nerve conduction studies, electromyography as well as ultrasound of peripheral nerves and tibial anterior muscle were performed. Cytokine levels were analyzed by a bead-based multiplex assay system. RESULTS: Of 248 screened patients, 35 patients were included at median of 6 days (IQR: 8) after admission to intensive care unit. Axonal damage was the main feature of CIPNM. At the peak of CIPNM (7 days after inclusion), nerve ultrasound showed cross-sectional area increase of tibial nerve as a sign of inflammatory edema as well as hypoechoic nerves as a possible sign of inflammation. Cytokine analyses showed signs of monocyte and macrophage activation at this stage. Fourteen days after inclusion, cytokines indicated systemic immune response as well as profiles associated to neovascularization and regeneration. CONCLUSIONS: Exploratory neuromuscular ultrasound and cytokine analyses showed signs of inflammation like macrophage and monocyte activation at the peak of CIPNM followed by a systemic immune response parallel to axonal damage. This underlines the role of both axonal damage and inflammation in pathogenesis of CIPNM.

Serum neurofilament light chain as outcome marker for intensive care unit patients.

OBJECTIVE: Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. METHODS: Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. RESULTS: NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). CONCLUSION: NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.

High-Resolution Nerve Ultrasound to Assess Nerve Echogenicity, Fascicular Count, and Cross-Sectional Area Using Semiautomated Analysis.

BACKGROUND AND PURPOSE: Little is known about echogenicity and fascicular structure observed in high-resolution nerve ultrasound (HRUS) in both healthy subjects and patients with peripheral nerve disease. The aim of this study was to evaluate the reliability of echogenicity, fascicle count, and fascicle size analysis, to create standard values and compare these parameters to patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Median, ulnar, radial, tibial, and fibular nerve of 79 healthy subjects and patients were scanned by one examiner using HRUS. Image analysis regarding echogenicity, fascicle count, and fascicle cross-sectional area (CSA) was performed by two independent raters semiautomatically using ImageJ. Pearson correlation coefficient r reflected interrater reliability (IR), and intraclass correlation coefficient (ICC) determined intrarater reliability (IAR). Results of healthy subjects were compared to 20 patients with CIDP by analysis of variance. RESULTS: IR was very good for echogenicity (r = .9) and good for fascicle count and size of the largest fascicle (r = .64/.56). IAR was very good for all three parameters (ICC = .9/.83/.74). Healthy subjects had a wide range of values. CIDP patients were in range of healthy subjects. Clinically progressive CIDP patients (defined as an increase in Overall Disability Sum Score by ≥1 point) had a lower fraction of black than healthy controls and stable CIDP patients (P < .001). CONCLUSION: Semiautomated evaluation of echogenicity, fascicle count, and fascicle CSA is reliable. Cutoff values to differentiate between healthy persons and CIDP do not exist. Echogenicity is useful for detecting clinically progressive CIDP patients and should be used in clinical context or intraindividual course.

Cross-sectional area in median and ulnar nerve ultrasound correlates with hand volume.

BACKGROUND: The influence of demographic and anthropometric factors on nerve cross-sectional area (CSA) reference values in high-resolution ultrasound was evaluated in a prospective observational study. METHODS: We measured CSA of median, ulnar, radial, and sural nerves in 80 healthy adults from 18 to 98 years of age. Pearson's correlation and multiple linear regression with age, gender, body mass index, and hand volume were calculated. RESULTS: Ulnar and median nerve CSA showed a significant positive correlation with ipsilateral hand volume. Median nerve CSA in the left forearm (mean, 6.2 mm2 ; SD, 1.2) increased by 0.006 mm2 (SE = 0.002; P < .001) per cm3 of hand volume, resulting in a difference of 1.9 mm2 predictable by hand volume (mean, 326 cm3 ; SD, 81; range, 180-500). CONCLUSIONS: The observed correlation of CSA and hand volume may influence the interpretation of CSA values in patients with very large or small hands.

Neuroimaging markers of clinical progression in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: One of the main goals of novel, noninvasive imaging techniques like high-resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) is the prediction of treatment response for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A total of 17 patients with CIDP were examined prospectively at baseline and every 9 months over a period of 18 months using CCM to quantify corneal nerve degeneration markers and immune cell infiltration as well as HRUS to detect changes of the cross-sectional area (CSA) of the peripheral nerves. Additionally, skin biopsy of the distal and proximal leg as well as quantitative sensory testing were performed at the first follow-up visit. RESULTS: A value of more than 30 total corneal cells/mm2 in CCM at baseline identified patients with clinical progression with a sensitivity/specificity of 100% in our cohort. Corneal nerve fiber density and length remained low and stable over the study period and intra-epidermal fiber density was markedly reduced in the majority of the patients. Furthermore, an increase in Bochum ultrasound score (BUS), which summarizes the CSA of the ulnar nerve in Guyons' canal, the ulnar nerve in the upper arm, the radial nerve in the spiral groove and the sural nerve between the gastrocnemius muscle, and a maximum BUS of 4 at study initiation identified patients with disease progression (sensitivity 80%, specificity 88%). CONCLUSIONS: BUS and corneal total cell infiltration seem to represent early markers for clinical progression in CIDP, thus having the potential to identify at-risk patients and impact treatment decisions.

Intrathecal triamcinolone acetonide exerts anti-inflammatory effects on Lewis rat experimental autoimmune neuritis and direct anti-oxidative effects on Schwann cells.

BACKGROUND: Corticosteroids dominate in the treatment of chronic autoimmune neuropathies although long-term use is characterized by devastating side effects. METHODS: We introduce the intrathecal application of the synthetic steroid triamcinolone (TRIAM) as a novel therapeutic option in experimental autoimmune neuritis in Lewis rats RESULTS: After immunization with neuritogenic P2 peptide, we show a dose-dependent therapeutic effect of one intrathecal injection of 0.3 or 0.6 mg/kg TRIAM on clinical and electrophysiological parameters of neuritis with a lower degree of inflammatory infiltrates (T cells and macrophages) and demyelination in the sciatic nerve. In vitro studies in Schwann cell cultures showed an increased expression of IL-1 receptor antagonist and reduced expression of Toll-like receptor 4 after incubation with TRIAM as well as a protective effect of TRIAM against oxidative stress after H2O2 exposure. CONCLUSION: Intrathecal TRIAM application could be a novel immunomodulatory and potentially neuroprotective option for autoimmune neuropathies with a direct effect on Schwann cells.

Prospective Study of the Clinical, Electrophysiologic, and Sonographic Characteristics of Oxaliplatin-Induced Neuropathy.

BACKGROUND AND PURPOSE: Oxaliplatin-induced neuropathy is a major dose limiting side effect of the highly effective combination chemotherapy with oxaliplatin, irinotecan, and 5-fluorouracil (FOLFIRINOX) in patients with metastastic pancreatic cancer. We present the first longitudinal sonographical-electrophysiological study on oxaliplatin-induced neuropathy. METHODS: Thirteen patients with metastatic pancreatic cancer underwent clinical, sonographic, and electrophysiological evaluation before, 3 and 7 months after treatment with 12 two-week cycles of FOLFIRINOX. RESULTS: The majority of patients (61%) developed symptoms and electrophysiological signs of a length-dependent sensorimotor axonal neuropathy 7 months after treatment initiation. Oxaliplatin-induced neuropathy presented with a cross-sectional area (CSA) increase of mostly the tibial and fibular nerve, which developed parallel or prior to clinical signs and electrophysiological changes. Furthermore, isolated CSA at entrapment sites of the upper and lower extremities was measured without relevant symptoms. No correlation between sonographic and electrophysiological findings or clinical severity was detected. CONCLUSIONS: Oxaliplatin-induced neuropathy is characterized by an axonal length-dependent nerve affection presenting with a combination of sonographical and electrophysiological alterations.

Clinical, Sonographic, and Electrophysiologic Longitudinal Features of Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND AND PURPOSE: Several studies have aimed to find potential biomarkers to simplify the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) and to monitor and predict the disease course. However, reliable markers are still lacking. We aimed to investigate whether high-resolution nerve ultrasound (HRUS) is suitable for monitoring the long-term clinical course of CIDP. METHODS: Twenty patients fulfilling the definite diagnostic criteria of CIDP received clinical examination, evaluation of the INCAT (inflammatory neuropathy cause and treatment) overall disability sum score (ODSS) as well as nerve conduction studies, and HRUS every 6 months over a median follow-up time of 34 months. Patients were divided into clinically stable/regressive disease course or progressive disease course according to the development of the ODSS. RESULTS: The intranerve cross-sectional-area (CSA) variability of the nerves of the lower extremity increased with disease progression, whereas it remained unchanged in patients with a stable or remitting disease course. CONCLUSION: Nerve ultrasound can be used as a method to objectify the long-term disease course in CIDP patients. The intranerve CSA variability is suitable for monitoring the clinical course of patients with CIDP.

Nerve echogenicity and intranerve CSA variability in high-resolution nerve ultrasound (HRUS) in chronic inflammatory demyelinating polyneuropathy (CIDP).

OBJECTIVE: HRUS is increasingly being used in the diagnosis and evaluation of autoimmune neuropathies such as CIDP. Recently, studies focused not only on changes of nerves size, but also the fascicular structure and the echogenicity changes in CIDP. However, little is known about the alterations of echogenicity in the long-term course in CIDP. The aim of this study was to evaluate echogenicity in CIDP patients in a long-term follow-up period and to analyze the benefit of the evaluation of echogenicity compared to nerve size. METHODS: 20 patients fulfilling the definite diagnostic criteria of CIDP received clinical examination, nerve conduction studies and HRUS every 6 months over a median follow-up time of 34 months. Patients were divided into clinically stable/regressive disease course or progressive disease course according to the development of the inflammatory neuropathy cause and treatment overall disability sum score. Echogenicity of peripheral nerves was measured semi-automated and quantitative. Echogenicity was divided into three classes by fraction of black: hypoechogenic, mixed hypo-/hyperechogenic, hyperechogenic. RESULTS: Patients with hyperechogenic arm nerves more frequently show clinical worsening, whereas patients with hypoechogenic arm nerves remain stable or even improved over time. In the long-term course of the disease, echogenicity mostly did not change, and if changes occured echogenicity did not correspond to ODSS changes. CONCLUSION: Echogenicity of the arm nerves in CIDP may be used as a prognostic marker, but not as a follow-up tool for evaluating clinical changes. Further studies in a larger cohort are needed to confirm these results.

Treatment of an acute motor and sensory axonal neuropathy with propionate in a 33-year-old male.

BACKGROUND: The aim of this work was to report a case of an acute motor and sensory axonal neuropathy (AMSAN) treated with propionate to evaluate its therapeutic potential in AMSAN. MATERIALS AND METHODS: The patient was investigated by clinical examination, electroneurography, high-resolution nerve ultrasound and confocal corneal microscopy at baseline and the 2 month follow up. We compared the outcome with those of five other patients with acute motor axonal neuropathy (AMAN) and AMSAN of who were referred to our neurology department in the past 5 years. RESULTS: Considering the poor prognosis of patients with acute axonal neuropathies and in comparison with the previously treated patients with AMAN or AMSAN in our clinic, the regression of our patient's symptoms and the improvement in the additional examinations under propionate seemed exceptionally good. CONCLUSION: Propionate may have an additional therapeutic effect in autoimmune inflammatory neuropathies.

High-resolution nerve ultrasound and magnetic resonance neurography as complementary neuroimaging tools for chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: We present a clinical, electrophysiological, sonographical and magnetic resonance neurography (MRN) study examining the complementary role of two neuroimaging methods of the peripheral nervous system for patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Furthermore, we explore the significance of cross-sectional area (CSA) increase through correlations with MRN markers of nerve integrity. METHODS: A total of 108 nerve segments on the median, ulnar, radial, tibial and fibular nerve, as well as the lumbar and cervical plexus of 18 CIDP patients were examined with high-resonance nerve ultrasound (HRUS) and MRN additionally to the nerve conduction studies. RESULTS: We observed a fair degree of correlation of the CSA values for all nerves/nerve segments between the two methods, with a low random error in Bland-Altman analysis (bias = HRUS-CSA - MRN-CSA, -0.61 to -3.26 mm). CSA in HRUS correlated with the nerve T2-weighted (nT2) signal increase as well as with diffusion tensor imaging parameters such as fractional anisotropy, a marker of microstructural integrity. HRUS-CSA of the interscalene brachial plexus correlated significantly with the MRN-CSA and nT2 signal of the L5 and S1 roots of the lumbar plexus. CONCLUSIONS: HRUS allows for reliable CSA imaging of all peripheral nerves and the cervical plexus, and CSA correlates with markers of nerve integrity. Imaging of proximal segments as well as the estimation of nerve integrity require MRN as a complementary method.

Severe refractory CIDP: a case series of 10 patients treated with bortezomib.

Treatment options for patients with aggressive chronic inflammatory demyelinating neuropathy are limited and include the anti-CD20 antibody rituximab and the immunosuppressive regime cyclophosphamide. We aimed to investigate retrospectively the efficacy of bortezomib, a proteasome inhibitor tackling highly metabolically active cell types such as plasma cells, in a case series of 10 treatment refractory CIDP patients. All patients reported showed a deterioration of the clinical CIDP scores under first-line treatment or escalating treatment with cyclophosphamide or rituximab. One or two cycles of bortezomib treatment (each cycle with 1.3 mg/m2 administered s.c. on days 1, 4, 8, and 11) stabilized the majority of the patients (n = 6) during treatment and even improved clinical and electrophysiological parameters of four patients up to 1 year later. No relevant side-effects were reported. Two patients received autologous peripheral blood stem cell transplantation after bortezomib, which led to fatal infections. We conclude that bortezomib could be an attractive escalating treatment option with a good side-effect profile for patients with treatment refractory CIDP.