Nonsystemic Vasculitic Neuropathy: Update on Diagnosis, Classification, Pathogenesis, and Treatment

ArticleinFrontiers of neurology and neuroscience 26:26-66 · February 2009with17 Reads
DOI: 10.1159/000212368 · Source: PubMed
The primary systemic vasculitides are autoimmune disorders characterized by chronic immune responses directed against vascular structures. They commonly affect small or medium-sized vessels in the peripheral nervous system (PNS), producing vasculitic neuropathies. Some patients develop vasculitis clinically restricted to the PNS, known as nonsystemic vasculitic neuropathy (NSVN), the most commonly encountered vasculitic neuropathy in pathologically based series. Diabetic and nondiabetic radiculoplexus neuropathies are clinical variants of NSVN. NSVN is clinically similar to systemic vasculitis-associated neuropathies except for reduced severity. Patients most commonly present with progressive, stepwise pain, weakness, and numbness over multiple months. Almost all exhibit a multifocal or asymmetric, distally accentuated pattern of involvement. The most commonly affected nerves are the common peroneal nerve in the leg and the ulnar nerve in the arm. Sedimentation rate is mildly to moderately elevated in 50%; other markers of systemic inflammation are generally normal. Electrodiagnostic studies reveal a predominantly axonal, asymmetric, sensorimotor polyneuropathy, but pseudo-conduction blocks may occur. Definite diagnosis requires biopsy evidence of vascular inflammation and signs of active or remote vascular damage. In biopsies lacking definite vasculitis, the diagnosis is suspected if axonal alterations are accompanied by perivascular inflammation and such supportive features as Wallerian-like degeneration, asymmetric fiber loss, hemosiderin, vascular immune deposits, neovascularization, myofiber necrosis/regeneration, focal perineurial damage, and endoneurial purpura. NSVN preferentially affects larger epineurial arterioles. Epineurial infiltrates are composed primarily of T cells and macrophages, suggesting that cellular cytotoxicity is the primary effector mechanism. Systemic vasculitides with progressive neuropathy are usually treated with cyclophosphamide and prednisone. No randomized controlled trial of therapy has been performed in NSVN, but data from retrospective cohorts suggest that combination therapy is more effective than steroid monotherapy. Once remission has been induced, cyclophosphamide should be replaced with azathioprine or methotrexate. Refractory patients can be treated with intravenous immunoglobulin, mycophenolate, rituximab, infliximab, or alemtuzumab. Although long-term outcome is reasonably good, more than one third of patients relapse, infrequent patients die from the disease or its treatment, and still others develop chronic pain.
    • "Supportive of this concept, many patients with NSVN exhibit subclinical vascular/perivascular inflammation in regional muscles and skin. Moreover, emerging evidence suggests that patients with NSVN are less likely to exhibit necrotizing vasculitis than those with SVN (Collins et al., 2009). Our three patients (patients 3, 4 and 5) with NSVN had type 3 vasculitic lesions on sural nerve biopsy. "
    [Show abstract] [Hide abstract] ABSTRACT: Multiple mononeuropathy is an unusual form of peripheral neuropathy involving two or more nerve trunks. It is a syndrome with many different causes. We reviewed the clinical, electrophysiological and nerve biopsy findings of 14 patients who suffered from multiple mononeuropathy in our clinic between January 2009 and June 2013. Patients were diagnosed with vasculitic neuropathy (n = 6), perineuritis (n = 2), chronic inflammatory demyelinating polyradiculoneuropathy (n = 2) or Lewis-Sumner syndrome (n = 1) on the basis of clinical features, laboratory data, electrophysiological investigations and nerve biopsies. Two patients who were clinically diagnosed with vasculitic neuropathy and one patient who was clinically diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy were not confirmed by nerve biopsy. Nerve biopsies confirmed clinical diagnosis in 78.6% of the patients (11/14). Nerve biopsy pathological diagnosis is crucial to the etiological diagnosis of multiple mononeuropathy.
    Full-text · Article · Mar 2015
    • "Vasculitic neuropathy occurs as a primary or as a secondary phenomenon and can be restricted to the peripheral nervous system only. Various underlying pathogenic mechanisms, such as immune complex deposition, cell mediated interactions, and antineutrophil cytoplasmic antibody (ANCA) associated processes are discussed and have been extensively reviewed (Collins and Periquet-Collins, 2009; Jennette and Falk, 2007; Said and Lacroix, 2005). In most cases the initiating event is unknown, and a self-sustaining circuit attracts and activates inflammatory leucocytes in the wall of vessels. "
    [Show abstract] [Hide abstract] ABSTRACT: To investigate molecular mechanisms of peripheral nerve vasculitis, gene expression patterns in archived frozen sural nerve biopsies from patients with vasculitic neuropathy were compared to control nerves by DNA microarray technology. There was a striking upregulation of mRNA of genes involved in immune system processes. Of special interest was the activation of immunoglobulin genes, such as IGLJ3, IGHG3, IGKC, and IGL, and of several chemokines, such as CXCL9 or CCR2. Genes involved in vascular proliferation or remodelling such as CXC31 and AIF were also upregulated. Among the downregulated genes were the Krüppel-Like Transcription Factors KLF2, KLF4 and the nuclear orphan receptor NR4A1 genes known to be involved in endothelial cell activation. Thus, this gene expression profile analysis revealed that in peripheral nerve vasculitis a prominent activation of immune response related genes as well as genes involved in vascular proliferation is taken place, while genes inhibiting endothelial cell activation are down regulated. These data point to interesting mechanistic clues to the molecular pathogenesis of vasculitic neuropathies.
    Full-text · Article · Aug 2010
    • "No randomized clinical controlled trial of therapy has been done in patients with nonsystemic vasculitis neuropa- thy [23], but the majorities of retrospective data support the use of glucocorticoid and immunosuppressive. In refractory cases, it has been used intravenous immunoglobulin, mycophenolate, rituximab, infliximab, or alemtuzumab [24]. We suggest that patients with a polyneuropathy without apparent underlying disease should be suspected of having an isolated vasculitis of the peripheral nervous system. "
    [Show abstract] [Hide abstract] ABSTRACT: Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis) of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.
    Full-text · Article · Jan 2009
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