High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies.

Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis.

BACKGROUND AND PURPOSE: There are other options open to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are non-responders to conventional treatment, including immunosuppressive and immunomodulatory agents (IA). The aim of this study was to assess whether the use of IA is able to increase the number of responders. METHODS: Clinical and electrophysiological data of patients with refractory CIDP, followed at 10 Italian centres, were collected, and the clinical outcome (Rankin Scale) and drug side effects (SE) for the different therapies were analysed. RESULTS: A total of 110 patients were included. These patients underwent 158 different therapeutic procedures with IA. Seventy-seven patients were treated with azathioprine, 18 rituximab, 13 cyclophosphamide, 12 mycophenolate mofetil, 12 cyclosporine, 12 methotrexate, 11 interferon-alpha and three interferon beta-1a. The percentage of patients who responded to azathioprine (27%) was comparable to the percentage of responders to other therapies, after the exclusion of interferon beta-1a that was not effective in any of the three patients treated. The percentage of SE ranges from 8% (methotrexate) to 50% (cyclosporine). CONCLUSIONS: One-fourth of patients, refractory to conventional treatment, showed an improvement in their disability with IA. Methotrexate had the lowest SE; cyclosporine was associated with severe SE and often led to drug discontinuation.

Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature.

BACKGROUND: A few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). OBJECTIVE: To analyse the efficacy of rituximab in a large CIDP cohort. METHODS: A retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders. RESULTS: Nine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1-6) and lasted for a median period of 1 year (range, 1-5). CONCLUSIONS: Rituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.

Altered resting state attentional networks in diabetic neuropathic pain.

BACKGROUND: Chronic pain can be considered as a highly salient stimulus that continuously taxes the attentional and salience processing networks, thus interfering with cognitive abilities and, more specifically, consuming attentional resources. The aim of the paper was to explore whether and how diabetic neuropathic pain (NP) affects attentional networks. METHODS: The authors sought to achieve this by investigating resting state functional connectivity (rsFC) in diabetic NP patients and comparing it with that of matched healthy controls. RESULTS: NP patients showed a widespread reduction in connectivity in both the dorsal and ventral attentional networks, as well as in the dorsal anterior cingulated cortex (ACC), typically implicated in salience processing. The authors also found a generalised reduction in the length of functional connections in the NP group: in all the examined networks, the Euclidean distance between connected voxels was significantly shorter in patients than in controls. CONCLUSION: In diabetic NP, a parieto-fronto-cingulate network controlling attention to external stimuli is impaired. In line with previous studies, chronic pain can disrupt the synchrony of a common pool of brain areas, involved in self-monitoring, pain processing and salience detection.

A nationwide retrospective analysis on the effect of immune therapies in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: The guidelines for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) therapy suggest to use immunoglobulins (IVIg) and steroid as first-line therapies. Patients who do not respond to one of the two drugs should be switched to the other drug. We collected therapeutic outcome data in patients followed at 11 centres in order to document the clinical practice in Italy. METHODS: Clinical and electrophysiological data of patients with CIDP were entered into a central database. The clinical outcome (Rankin Scale) and drug side effects (SE) for first- and second-line therapies were recorded. RESULTS: A total of 267 patients were included. The percentage of responders (R) to first-line therapy [steroid or IVIg or plasma exchange (PE)] was 69%; this number increased to 81% when patients who switched to different therapies were included. Overall, the percentage of R to IVIg was similar to R to steroids (P = 0.07) and higher than R to PE (P < 0.001). Of the main therapies, PE frequently caused SE (19%), followed by steroids (12.5%) and IVIg (4%). CONCLUSIONS: Switching between traditional therapies increases the number of responder patients. IVIg was confirmed to be a therapy with low SE.

High prevalence of neuropathies in patients with end-stage liver disease.

OBJECTIVES: Peripheral neuropathy has been reported in association with end-stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. MATERIALS AND METHODS: In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. RESULTS: Sixty-five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory-motor neuropathies and sensory neuropathies, with a length-dependent pattern. CONCLUSION: Peripheral neuropathy and autonomic neuropathy are common in patients with end-stage liver disease with different etiology and correlate with the severity of the liver disease.

Pain affects the quality of life of neuropathic patients.

The aim of this study was to verify the extent to which the presence of pain affects the quality of life (QoL) of neuropathic patients. The patients were selected in our Department of Peripheral Nervous System Diseases. We enrolled 120 consecutive patients with chronic polyneuropathy who had not received continuous pain therapy during the two months preceding study entry, and administered them the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is affected not only by the presence of neuropathy, but also by the presence and intensity of pain: the physical aspect of the QoL correlated only weakly with the TNS, but pain was closely related to a worsening in this parameter; moreover, the mental domains of the SF-36 were only correlated with pain. Pain per se worsens the QoL of neuropathic patients, regardless of disease severity.

A further critical evaluation of requests for electrodiagnostic examinations.

The aim of this study was to evaluate the impact of electrophysiological (EDX) tests in the clinical management and diagnosis of patients, and the appropriateness of the referral diagnosis. A study was carried out in three electrodiagnostic services in the Torino area, over a 12-month period. In our study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients underwent EDX examinations including nerve conduction study, electromyography and repetitive stimulation test. Most patients had been sent for EDX tests by specialists. Specialists suspected mainly polyneuropathy, whilst general practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the requests were correctly formulated, 55% by general practitioners and 77% by specialists. There was a concordance between the results of the EDX tests and diagnostic hypothesis 40% of the time. This study confirms the usefulness and diagnostic impact of EDX examinations and evidences the amount of time and resources wasted as a result of incorrect or incomplete requests.

Differential diagnosis of chronic dysimmune demyelinating polyneuropathies with and without anti-MAG antibodies.

The distinction between chronic demyelinating polyneuropathies associated with IgM paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibodies (MAG-PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) relies on the anti-MAG antibodies assay. The aim of the study was to identify clinical and electrophysiological features suggesting a diagnosis of MAG-PN. Fourteen patients with MAG-PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological features suggestive of MAG-PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were significantly associated with the diagnosis of MAG-PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmune demyelinating polyneuropathies.