Chronic inflammatory demyelinating polyradiculoneuropathy: A role for haematopoietic stem cell transplantation?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical syndrome of a chronic progressive or relapsing and remitting, symmetrical, sensory and motor radiculoneuropathy. The immune reaction in CIDP is characterised by selective inflammation of peripheral nerves and is probably due to the interaction of cellular and humoral responses. Only three treatments for CIDP have demonstrated benefit in randomised studies, corticosteroids, plasma exchange and intravenous immunoglobulin. 25% of patients fail to respond or do not respond adequately to these treatments. Experimental data in animal models have shown that several autoimmune disorders, either congenital or acquired, can be transferred and/or treated by the transplantation of bone marrow stem cells. Haematopoietic stem cell transplantation (HSCT) has been performed with varying success in over 700 patients with autoimmune disorders throughout Europe. The experience in CIDP is very limited. This article will review current understanding of CIDP and experience of the use of HSCT in refractory CIDP.     

Circulating subsets and CD4+CD25+ regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disease of the peripheral nervous system that is probably autoimmune in origin. Different components of the adaptive and innate immunity may be responsible for the aberrant response towards nerve antigens. To investigate this, we examined lymphocyte subsets and regulatory T cell (Treg) function in the blood of CIDP patients, healthy controls (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON). We used flow cytometry to determine the frequency of monocytes, B cells, natural killer (NK) and NK-T cells, total and activated CD4⁺ and CD8⁺ T cells, effector memory and central memory CD4⁺ and CD8⁺ T cells, and CD4⁺CD25^highFoxp3⁺ Tregs. Treg function was studied after polyclonal stimulation and antigen specific stimulation with myelin protein peptides in CIDP and HC. There was an increased frequency of monocytes (p = 0.02) and decreased frequency of NK cells (p = 0.02) in CIDP compared with HC but not ON. There were no significant differences in other populations. Treg function was impaired in CIDP compared to HC (p = 0.02), whilst T cell proliferation to myelin protein peptides before and after depletion of Tregs was not different between patients and controls. This study shows increased circulating monocytes and reduced NK cells in CIDP. Although Treg frequency was not altered, we confirm that Tregs display a defect of suppressive function. Myelin protein peptides were not the target of the altered peripheral regulation of the immune response. The mechanisms of peripheral immune tolerance in CIDP and their relevance to the pathogenesis deserve further exploration.     

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.     

Nerve ultrasound in a case of chronic inflammatory demyelinating neuropathy

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune‐mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based mainly on the clinical presentation and electrophysiological detection of demyelination. Methods: Several MRI studies have demonstrated hypertrophy and abnormal enhancement of spinal nerve roots or brachial plexus in CIDP, but there have been only anecdotal reports of similar sonographic findings. Results: This article reports the sonographic findings of a CIDP case and includes a review of the literature and previously reported cases. Conclusions: This case report highlights the importance of sonography in the localization and recognition of focal nerve enlargements in patients with CIDP. This method could be a helpful tool in the diagnosis of conduction block in CIDP, especially in cases where a nerve segment cannot be explored easily with the inching technique. Systematic data are needed to confirm this observation. Muscle Nerve 47:443‐446, 2013     

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy

ObjectiveTo report the electrodiagnostic features of immune checkpoint inhibitor (ICI)-related neuropathy.MethodsWe retrospectively reviewed clinical presentations and electrodiagnostic features of 23 patients studied after receiving immune checkpoint inhibitors (ICIs). The presentations for electrodiagnostic evaluation included an acute neuropathy or neuromuscular junction disorder. We applied established electrodiagnostic criteria for polyneuropathy and acute demyelinating neuropathy.ResultsWe identified acute demyelinating neuropathy (13 cases), axonal sensory motor neuropathy (5), pure sensory neuropathy (4) and mononeuropathy (1). 13 patients had acute demyelinating neuropathy confirmed by demonstrating demyelination in 2 or more nerves; 3 additional patients had demyelination in only one nerve. Analysis of motor nerve conduction parameters revealed demyelination involving median and ulnar nerve distal motor latencies as well as median, ulnar and peroneal nerve conduction velocities. Conduction block was found in median, ulnar and peroneal nerves. The remaining one-third patients without demyelination had acute painful axonal neuropathy. Coexisting myopathic changes (6) and neuromuscular junction dysfunction (4) were also identified.ConclusionsOur findings suggest that, while immune-mediated motor nerve demyelination is the primary underlying mechanism of ICI-related neuropathy, axonal painful neuropathy can also be an important presentation. Early recognition and effective intervention may reduce morbidity and permanent disability.SignificanceElectrophysiological studies might be useful in the evaluation of ICI-related neuropathy.     

Incat disability score: A critical analysis of its measurement properties

Background: The INCAT (Inflammatory Neuropathy Cause and Treatment) disability score is a measure of activity limitation. It is used frequently as a primary endpoint in inflammatory polyneuropathy clinical trials. A comprehensive critical analysis of its measurement properties has not been performed. Methods: Critical analysis of measurement properties. Results: The INCAT disability score was derived based on items from Guy's Neurological Disability Scale (GNDS), a disability measure intended for application in multiple sclerosis. Strengths of the INCAT score include evaluation of upper and lower limb dysfunction, ease of administration (feasibility), high face validity, and high reliability. Weaknesses of the scale include concerns about methodological quality of validation studies; failure to properly capture activity limitations due to proximal arm weakness, or fatigue; heavy individual item weighting; and poor sensitivity for detection of clinically important change. Conclusions: Although the INCAT scale has been an effective tool in inflammatory polyneuropathy studies, its limitations may warrant development of new scales. Muscle Nerve 50:164–169, 2014