[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.

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.

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.

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.

Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies.

INTRODUCTION: In this study we evaluated a new neuropathy ultrasound protocol (NUP) for differentiating chronic immune-mediated neuropathies. METHODS: The NUP was evaluated in 110 patients with clinical presentations of chronic immune-mediated neuropathy. All patients were first evaluated clinically and electrophysiologically and divided into 4 polyneuropathy groups: (a) symmetric demyelinating; (b) symmetric axonal; (c) asymmetric demyelinating; and (d) asymmetric axonal. During step 2, the NUP was evaluated prospectively for all 4 study groups. RESULTS: Overall, the NUP led to correct classification in 42 of 49 (85.7%) patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 of 15 (86.9%) with multifocal motor neuropathy (MMN), and 5 of 5 (100%) with multifocal-acquired demyelinating sensory and motor neuropathy (MADSAM). The NUP had >80% sensitivity and specificity in distinguishing CIDP, MMN, and MADSAM in all 4 study groups. CONCLUSIONS: The NUP is a useful addition in the differential diagnosis of chronic immune-mediated neuropathies in everyday practice. Muscle Nerve 54: 864-871, 2016.

Facing the diagnostic challenge: Nerve ultrasound in diabetic patients with neuropathic symptoms.

INTRODUCTION: We describe the nerve ultrasound findings in patients with type II diabetes mellitus who have neuropathic symptoms and signs. METHODS: Fifty-five healthy controls and 44 diabetic patients underwent clinical, sonographic, and electrophysiological evaluation. Patients were studied at a mean of 14.3 years after disease onset. RESULTS: Nerve ultrasound revealed increased cross-sectional area (CSA) in peripheral nerves at compression sites (although no clinical symptoms were present) and noncompression sites. No correlation was detected between sonographic and electrophysiological findings. A CSA increase of the tibial nerve in the popliteal fossa was detected in 5 patients with neuropathic symptoms, although electrophysiology was normal. CONCLUSIONS: Nerve ultrasound revealed crucial morphological alterations in diabetic patients. CSA enlargement at compression sites indicates subclinical nerve affection and may indicate susceptibility to entrapment syndromes. CSA increase at noncompression sites despite normal electrophysiology suggests early morphological abnormalities. Further longitudinal studies are required to confirm our results. Muscle Nerve, 2015 Muscle Nerve 54: 18-24, 2016 Muscle Nerve 54: 18-24, 2016.

Nerve ultrasound in a case of multifocal motor neuropathy without conduction block.

INTRODUCTION: Multifocal nerve enlargements and ultrastructural changes either corresponding or not to sites of existing conduction blocks have been described in demyelinating polyneuropathies using multiple imaging techniques. METHODS: Using the emerging technique of peripheral nerve ultrasonography we investigated the peripheral nerves of a patient with multifocal motor neuropathy (MMN) without conduction block. RESULTS: In this case of MMN without conduction blocks we found multifocal nerve enlargements in the ultrasonography and electrodiagnostic signs of acute and chronic denervation associated with positive anti-GM1 IgM antibodies. CONCLUSIONS: This case shows that nerve ultrasound can be a complementary tool for diagnosing multifocal motor neuropathy without typical electrodiagnostic features.

Bochum ultrasound score versus clinical and electrophysiological parameters in distinguishing acute-onset chronic from acute inflammatory demyelinating polyneuropathy.

INTRODUCTION: The aim of this study was to evaluate whether a nerve ultrasound score (Bochum ultrasound score, BUS), clinical, and electrophysiological parameters could distinguish subacute chronic (CIDP) from acute inflammatory demyelinating polyneuropathy (AIDP). METHODS: Phase 1: The charts of 35 patients with polyradiculoneuropathy were evaluated retrospectively regarding BUS, clinical, and electrophysiological parameters (A-waves, sural nerve sparing pattern, sensory ratio>1). Phase 2: All parameters were evaluated prospectively in 10 patients with subacute polyradiculoneuropathy. RESULTS: Phase 1: A sum score of ≥2 points in BUS and the presence of sensory symptoms were significantly more frequent in the subacute CIDP group than in the AIDP group (P<0.001).The electrophysiological parameters showed no significant changes between the 2 groups. Phase 2: BUS (83.3%; 100%;), sensory symptoms (100%; 75%), absence of autonomic nervous system dysfunction (83.3%; 75%), or bulbar palsy (83.3%; 50%) showed the best sensitivity and specificity in distinguishing subacute CIDP from AIDP. CONCLUSIONS: BUS is a useful diagnostic tool for distinguishing subacute CIDP from AIDP.

The association between stress and headache: A longitudinal population-based study.

INTRODUCTION: We studied the association between stress intensity and headache frequency for tension-type headache (TTH), migraine and migraine with coexisting TTH (MigTTH). METHOD: We studied a population-based sample of 5159 participants (21-71 years) who were asked quarterly between March 2010 and April 2012 about headache and stress. Log-linear regression in the framework of generalized estimating equations was used to estimate regression coefficients presented as percent changes to describe the association between stress intensity (modified visual analog scale (VAS) from 0 to 100) and headache frequency (days/month) stratified by headache subtypes and age groups and adjusted for sex, age, frequent intake of acute pain drugs, drinking, smoking, BMI and education. RESULTS: TTH was reported in 31% participants (48.1 ± 12.5years, 51.5% women, 2.2 ± 3.9 mean headache days/month, 52.3 ± 26.7 mean stress), migraine in 14% (44.8 ± 11.3years, 73.3%, 4.5 ± 5.2 days/month, 62.4 ± 23.3), MigTTH in 10.6% (43.5 ± 11.5 years, 61.0%, 3.6 ± 4.8 days/month, 58.6 ± 24.1), 23.6% were unclassifiable, and 20.8% had no headache. In participants with TTH an increase of 10 points on VAS was associated with an increase of headaches days/month of 6.0% (adjusted). Higher effects were observed in younger age groups (21-30/31-40/41-50/51-60/61-71 years: 9.8/10.2/7.0/6.5/3.5%). Slightly lower effects were observed for migraine (4.3%, 8.1/5.1/3.4/6.3/0.3%) and MigTTH (4.2%, 5.5/6.8/6.9/5.8/-0.7%). CONCLUSION: Our study provides evidence for an association between stress intensity and headache frequency.

Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological, and clinical findings.

We present nerve ultrasound findings in multifocal motor neuropathy (MMN) and examine their correlation with electrophysiology and functional disability. Eighty healthy controls and 12 MMN patients underwent clinical, sonographic, and electrophysiological evaluation a mean of 3.5 years (standard deviation [SD] ± 2.1) after disease onset. Nerve ultrasound revealed significantly higher cross-sectional area (CSA) values of the median (forearm, p < 0.001), ulnar (p < 0.001), and tibial nerve (ankle, p < 0.001) when compared with controls. Electroneurography documented signs of significantly lower values of the motor conduction velocity and compound muscle action potentials (cMAPs) in the upper arm nerves (median, ulnar, radial, p < 0.001). A significant correlation between sonographic and electrophysiological findings in the MMN group was found only between cMAP and CSA of the median nerve at the upper arm (r = 0.851, p < 0.001). Neither nerve sonography nor electrophysiology correlated with functional disability. MMN seems to show inhomogeneous CSA enlargement in various peripheral nerves, with weak correlation to electrophysiological findings. Neither nerve sonography nor electrophysiology correlated with functional disability. Multicentre, prospective studies are required to prove the applicability and diagnostic values of these findings.

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.

Gray matter volume reduction reflects chronic pain in trigeminal neuralgia.

Trigeminal neuralgia (TN) is supposedly caused by an ectatic blood vessel affecting the trigeminal nerve at the root entry zone of the brain stem. Recent evidence suggests an additional central component within trigeminal pain-processing in the pathophysiology of TN. Therefore, we aimed to identify specific brain regions possibly associated with the development or maintenance of TN using magnetic resonance imaging (MRI) voxel-based morphometry (VBM). Sixty patients with classical TN were compared to 49 healthy controls. Eighteen patients had TN with concomitant constant facial pain, a condition previously described as a predictor of worse treatment outcome. We found gray matter (GM) volume reduction in TN patients compared to healthy controls in the primary somatosensory and orbitofrontal cortices, as well as the in the secondary somatosensory cortex, thalamus, insula, anterior cingulate cortex (ACC), cerebellum, and dorsolateral prefrontal cortex. GM volume decrease within the ACC, parahippocampus, and temporal lobe correlated with increasing disease duration in TN. There were no differences comparing patients with and without concomitant constant facial pain. No GM increase was found comparing patient subgroups with each other and with healthy controls. The observed changes probably reflect the impact of multiple, daily attacks of trigeminal pain in these patients similar to what was previously described in other chronic pain conditions and may be interpreted as adaptation mechanism to chronic pain in regard to neuronal plasticity. The ACC, parahippocampus and temporal lobe volume reduction in parallel with disease duration may point to a pivotal role of these structures in chronic pain.

Correlation of nerve ultrasound, electrophysiological, and clinical findings in post Guillain-Barré syndrome.

We aimed to correlate functional disability, electrophysiology, and nerve ultrasound in patients after Guillain-Barré syndrome (GBS). Seventy-five healthy controls and 41 post-GBS patients (mean 3.4 years, SD ± 2.91 years after onset) underwent clinical, sonographic, and electrophysiological evaluation. Compared to healthy controls, the post-GBS patients showed: (1) a mean Rasch-built Overall Disability Scale score of 31.8 (SD ± 11.6), modified Rasch-built fatigue severity scale score of 15.6 (SD ± 3.2), Medical Research Council sum score of 22 (SD ± 5.6); (2) electrophysiological signs of permanent axonal loss in the majority of the peripheral nerves; (3) sonographical evidence of higher cross-sectional area values (CSA) of the ulnar (elbow, p < 0.001), radial (spiral groove, p < 0.001), tibial nerve (popliteal fossa, p < 0.001) and brachial plexus (supraclavicular space, p < 0.001). No correlation between sonographic and electrophysiological findings was found. Neither nerve ultrasound nor electrophysiology correlated with muscle strength, overall disability, and fatigue scale. Compared to healthy controls, post-GBS patients had significant functional disability. Despite significant abnormalities in both electrophysiology and ultrasound compared to healthy controls, neither electrophysiology nor nerve ultrasound correlated with functional disability of these patients.

Epidemiological profiles of patients with chronic migraine and chronic tension-type headache.

BACKGROUND: We evaluated risk factors associated with chronic headache (CH) such as age, gender, smoking, frequent drinking of alcoholic beverages (drinking), obesity, education and frequent intake of acute pain drugs to test their usefulness in clinical differentiation between chronic migraine (CM) and chronic tension-type headache (CTTH). METHODS: We used baseline data from the population-based German Headache Consortium Study including 9,944 participants aged 18-65 years, screened 2003-2005, using validated questionnaires. CM and CTTH were defined according to IHS criteria. Multinominal logistic regression analyses were used to investigate the association of CM or CTTH with risk factors by estimating odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: The prevalence of CH was 2.6% (N = 255, mean age 46 ± 14.1 years, 65.1% women), CM 1.1% (N = 108, 45 ± 12.9 years, 73.1%), CTTH 0.5% (N = 50, 49 ± 13.9 years, 48.0%). Participants with CM compared to CTTH were more likely to be female (OR: 2.34, 95%CI: 1.00-5.49) and less likely to drink alcohol (0.31, 0.09-1.04). By trend they seemed more likely to smoke (1.81, 0.76-4.34), to be obese (1.85, 0.54-6.27), to report frequent intake of acute pain drugs (1.68, 0.73-3.88) and less likely to be low educated (0.72, 0.27-1.97). CONCLUSIONS: We concluded that the careful assessment of different risk factors might aid in the clinical differentiation between CM and CTTH.

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.

Prevalence of trigeminal neuralgia and persistent idiopathic facial pain: a population-based study.

OBJECTIVE: To estimate the lifetime prevalence of trigeminal neuralgia (TN) and persistent idiopathic facial pain (PIFP) in a population-based sample in Germany. METHODS: A total of 3336 responders of 6000 contacted inhabitants of the city of Essen in Germany were screened using a self-assessment questionnaire. 327 individuals, who reported recurrent facial pain and randomly selected 150 (5% of 3009) screening negative subjects, received a phone interview by one of six neurologists and if necessary a face-to-face examination. Those with suspected TN or PIFP following the phone interview underwent neurological examination by two neurologists who were unaware of the presumed diagnosis. A random group of 25 (10% of 247) phone interview negative subjects was examined face-to-face. All suspected cases of PIFP received otorhinolaryngological examination and diagnostic cranial magnetic resonance imaging (MRI). In TN patients the number of vessel-nerve contacts was determined by thin-slice cranial MRI. RESULTS: Lifetime prevalence of TN was estimated to be 0.3% [10 of 3336; 95% CI 0.1-0.5%], of PIFP 0.03% [1 of 3336; 95% CI < 0.08%]. Thin-slice cranial MRI detected five vessel-nerve contacts and no symptomatic lesions in the 10 TN patients. CONCLUSIONS: This large population-based study revealed that TN and PIFP are rare facial pain disorders.

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.

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.

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.

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.