Erdita Peci

Subcutaneous immunoglobulin in CIDP and MMN: a different long-term clinical response?

Subcutaneous immunoglobulin (SCIg) has been recently proposed as an effective alternative to intravenous immunoglobulin (IVIg) for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) treatment. The non-inferiority of SCIg over IVIg has been recently confirmed by a 4-month multicentre Italian observational study,1 where a similar efficacy was observed between the two therapies, with the SCIg showing possible advantages of stable plasmatic concentration2 and independence from hospital care. Here we report the 2-year experience of six Italian Neurological Centres, describing the long-term clinical outcomes of 66 patients (45 CIDP and 21 MMN) who were shifted from IVIg to SCIg. All the CIDP and MMN patients treated with SCIg between 2009 and 2014 were considered, including patients with a previous documented response to IVIg (at least 6 months), and a wear-off effect between each IVIg infusion documented by a worsening of at least 1 point at the Overall Neuropathy Limitation Scale (ONLS). Adherence to therapy was the primary outcome measure, while quality of life and clinical predictors of long-term disability were analysed as secondary outcomes. The clinical assessments were regularly performed by means of the ONLS, the Medical Research Council (MRC) scale in eight-muscle group bilaterally, and Life Quality Index (LQI). Clinical worsening was defined as increase of ≥1 ONLS point, requiring augmentation of SCIg dose, SCIg/IVIg combination therapy, or a return to IVIg for stabilising the clinical conditions. SCIg was administered at the patients home, as previously described,1 converting the IVIg dose to an equivalent SCIg dose (20% solution of immunoglobulin ready-to-use) delivered via a programmable infusion pump. All patients signed a written informed consent, and ethical committee approval was obtained (CEI—629 Prot. n 0010675, 25 January 2013). Statistical analyses were carried out utilising the Wilcoxon, Mann-Whitney and Friedman non-parametric tests, Cox proportional hazard regression …

Short-Term Efficacy of Ultramicronized Palmitoylethanolamide in Peripheral Neuropathic Pain

Introduction. This study evaluates the efficacy of palmitoylethanolamide ultramicronized (PEA-um) as an add-on treatment in patients with diabetic or traumatic neuropathic pain (NP). Methods. 30 patients with chronic NP were assessed with Visual Analogue Scale (VAS), NP Symptom Inventory (NPSI), and Health Questionnaire Five Dimensions (EQ-5D), both at baseline and after 10 and 40 days of treatment with 1200 mg/die of PEA-um. All other therapies were maintained stable during the follow-up period. Results. VAS mean score significantly improved within the first 10 days, ranging from 8.20 ± 1.53 to 6.40 ± 1.83 (P < 0.002), with a further decrease to 5.80 ± 2.04 (P < 0.001) after 40 days of PEA-um administration. Moreover, NPSI total score improved from 5.2 ± 1.5 to 3.8 ± 2.1 (P: 0.025) and EQ-5D ranged from −0.30 ± 0.65 to 0.5 ± 0.34 (P < 0.001) between T0 and T2. Conclusions. This study reports the prospective short-term efficacy data of oral PEA-um in patients with diabetic or traumatic NP. A significant improvement was observed both in VAS and NPSI scores and in quality of life scales after 40 days of treatment, although some limitations should be considered, including the short followup and the open-label study design.

Improvement of quality of life in patients with chronic inflammatory demyelinating polyneuropathy shifting from 16 to 20% subcutaneous immunoglobulins.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, demyelinating neuropathy with an assumed autoimmune-mediated pathogenesis. A number of published cases indicate that there may be potential for use of subcutaneous immunoglobulins (SCIg) as a treatment of CIDP [1–4]. Subcutaneous immunoglobulin treatment at a concentration of 20 % has been available now for more than a year. This product is administered at a total of 10 g per infusion through a tailored pump. The higher concentration makes for a reduction in the infusion rate required per week compared to the previously available product at a 16 % concentration. We selected a group of 10 patients with CIDP, responders to previous treatment with intravenous immunoglobulins and SCIg 16 % (dosage of the first cycle 2 g/kg/month, following dosage 1 g/kg/month). The patients, six males and four females, had mean age of 54 years (range 24–68), disease duration was 6.5 years (range 2.5–12.5), and the mean monthly dose of SCIg was 71.6 g. The patients were defined according to the PNS/EFNS criteria [5]. The Institutional Review Boards approved the study protocol. The aim of our study was to determine whether the use of SCIg at 20 % concentration varied the clinical response and quality of life (QoL) of patients compared to previous treatment with SCIg 16 %. In particular the SCIg 20 % having higher concentration can be infused in greater quantities in a reduced volume of liquid, and then with a lower number of weekly administrations. It has never been clarified whether the reduction in the number of administrations, and therefore, the highest time elapsed between them, can influence the clinical response. The study was divided into two parts. In the first part, the patients substituted the SCIg treatment at a concentration of 16 % with one at 20 % at the same time intervals, whilst maintaining the same doses by keeping the pump below its maximum delivery capacity. The aim of this first part was that of comparing the efficacy of the two products. The frequency and the time of the infusions with SCIg at 20 % concentration was then reduced at the third month upgrading the pump to its maximum output, so as to evaluate if the same efficacy could be obtained with a reduced infusion rate at the same total month dose. The patients were evaluated during SCIg treatment at 16 % (T0); after the first 3 months of SCIg treatment at 20 % (T1) and after a further 3 months with reduced infusion rates (T2), by the: (a) Medical Research Council (MRC) sum score; (b) Overall Neuropathy Limitation Scale (ONLS); (c) INCAT Sensory Sum Score (SSS); (d) Life Quality Index (LQI). No patients dropped out of the study and none had any adverse events. No relevant variations in the evaluation indexes (MRC, ONLS and SSS) were noted at either T1 or T2, whilst the LQI showed significantly higher scores between T1 and T2 (Table 1). Therefore, our data document that the efficacy of SCIg treatment at 20 % equals that of infusions at a D. Cocito (&) E. Peci E. Spagone L. Lopiano Neurologia IV, Department of Neurosciences, University of Turin, Via Cherasco 15, 10126 Turin, Italy e-mail: dariococito@yahoo.it

Subcutaneous vs. intravenous immunoglobulin in CIDP: pharmacokinetic and clinical response

Dear Editor, Subcutaneous immunoglobulin (SCIg) represents an innovative and effective alternative to intravenous immunoglobulin (IVIg) for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (Cocito et al., 2014; 2015). Different tolerability profiles have been reported between SCIg and IVIg, with the SCIg possible advantages of fewer side effects and greater independence from hospital care (Markvardsen et al., 2013; Rajabally, 2014). However, the two routes of administration are associated with a distinctive pharmacological profile (Eftimov et al., 2009), which may result in a differential clinical efficacy. We compare the pharmacokinetic data of eight CIDP patients shifted from IVIg monthly infusions to SCIg weekly administrations, evaluating the possible correlations between clinical response and IgG plasma levels. All patients were receiving IVIg for at least 6 months, reporting a “wear-off effect” between each infusion (increase of≥ 1 point at the inflammatory neuropathy cause and treatment [INCAT] score and/or decrease of≥1 point at the medical research council [MRC] scale). IVIg monthly dose (average dose: 1.25± 0.38 g/ kg/month; ranging from 1 to 2 g/kg/month, according to the individual clinical response) was converted to an equivalent dose of SCIg (20% solution of immunoglobulin ready-to-use) delivered via a programmable pump at the patient’s domicile. The shift from IVIg to SCIg was due to fluctuations in clinical response (wear-off) and patient’s desire of greater independence from hospital care (IVIg administration at the patient’s domicile is not allowed in Italy). Blood samples (5 ml), clinical scales (INCAT and MRC) and Martin vigorimeter measurements were collected immediately before the first day (T-1) and after the second day (T0) of the last IVIg cycle, and at the following time-points: (1) before the first SCIg administration (2 weeks after the last IVIg

CIDP-like neuropathies in graft versus host disease.

Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic review of the CIDP‐like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti‐ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background.

Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP.

Atypical CIDP: diagnostic criteria, progression and treatment response. Data from the Italian CIDP Database

Objectives A few variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been described, but their frequency and evolution to typical CIDP remain unclear. To determine the frequency and characteristics of the CIDP variants, their possible evolution to typical CIDP, and treatment response. Methods We applied a set of diagnostic criteria to 460 patients included in a database of Italian patients with CIDP. Clinical characteristics and treatment response were reviewed for each patient. The Kaplan-Meier curve was used to estimate the progression rate from atypical to typical CIDP. Results At the time of inclusion, 376 (82%) patients had a diagnosis of typical CIDP while 84 (18%) had atypical CIDP, including 34 (7%) with distal acquired demyelinating symmetric neuropathy (DADS), 17 (4%) with purely motor, 17 (4%) with Lewis-Sumner syndrome (LSS) and 16 (3.5%) with purely sensory CIDP. Based on retrospective review of the symptoms and signs present at onset and for at least 1 year, 180 (39%) patients had an initial diagnosis compatible with atypical CIDP that in 96 (53%) patients evolved to typical CIDP. Mean disease duration was longer in patients evolving to typical CIDP than in those not evolving (p=0.0016). Patients with DADS and LSS had a less frequent response to immunoglobulin than those with typical CIDP, while patients with purely motor and sensory CIDP had a similar treatment response. Conclusions The proportion of patients with atypical CIDP varies during the disease course. DADS and LSS have a less frequent response to intravenous immunoglobulin compared with typical CIDP, raising the possibility of a different underlying pathogenetic mechanism.