Nonsystemic Vasculitic Neuropathy Research Articles

Top 10 Clinical Pearls in Vasculitic Neuropathies.

Vasculitic neuropathies are a diverse group of inflammatory polyneuropathies that result from systemic vasculitis (e.g., polyarteritis nodosa, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis), vasculitis resulting from rheumatological disorders (e.g., rheumatoid arthritis and Sjögren's syndrome), paraneoplastic conditions, viruses, and medications. Occasionally, vasculitis is restricted to the peripheral nerves and termed nonsystemic vasculitic neuropathy. Presenting with an acute or subacute onset of painful sensory and motor deficits, ischemia to individual peripheral nerves results in the classic "mononeuritis multiplex" pattern. Over time, overlapping mononeuropathies will result in a symmetrical or asymmetrical sensorimotor axonal polyneuropathy. The diagnosis of vasculitic neuropathies relies on extensive laboratory testing, electrodiagnostic testing, and nerve and/or other tissue biopsy. Treatment consists primarily of immunosuppressant medications such as corticosteroids, cyclophosphamide, rituximab, methotrexate, or azathioprine, in addition to neuropathic pain treatments. Frequently, other specialists such as rheumatologists, pulmonologists, and nephrologists will comanage these complex patients with systemic vasculitis. Prompt recognition of these conditions is imperative, as delays in treatment may result in permanent deficits and even death.

Non-Eosinophilic Granulomatosis with Polyangiitis Vasculitic Neuropathy: An Overview

Vasculitic neuropathy is commonly associated with systemic vasculitis, leading to ischemic damage to the peripheral nerves and axonal degeneration. The typical clinical manifestation of vasculitic neuropathy is a sensory-dominant multiple mononeuropathy often accompanied by pain. Although vasculitic neuropathy is caused by various systemic diseases, ANCA-associated vasculitis, secondary systemic vasculitis linked to various collagen diseases, and non-systemic vasculitic neuropathy hold particular significance. A comprehensive understanding of vasculitic neuropathy is crucial for its early diagnosis, contributing to an improved prognosis for this condition.

Rituximab in non-systemic vasculitic neuropathy: a single-center experience

ObjectivesThis case series reports clinical features and outcome of four patients with non-systemic vasculitic neuropathy (NSVN) treated with the anti-CD20 agent rituximab.MethodsClinical, electrophysiological and biopsy data were retrospectively obtained and evaluated. Only patients with pathological definite or probable NSVN were included. Extensive clinical and laboratory work-up excluded systemic vasculitis. Follow-up data for at least 12 months and up to five years is provided. Outcome of the patients was assessed using the MRC-Sum Score, Prineas Score and Neurological Symptom Score.ResultsTwo of four patients treated with rituximab achieved disease remission and one patient remained stable under anti-CD20 therapy after a required treatment switch due to toxic side effects of cyclophosphamide. One patient deteriorated under rituximab induction. Rituximab was well tolerated in all patients.DiscussionAnti-CD20 therapy might be an alternative in NSVN patients requiring further treatment escalation or treatment switch due to side effects of corticosteroids or cyclophosphamide.

Modern Perspectives on Peripheral Neuropathology

Recent advances in genetic and antibody testing have limited pathological examination of peripheral nerve specimens. However, when examining peripheral neuropathological findings from a modern perspective, there is often an opportunity to comprehend previously unnoticed observations upon re-examining the same specimen. For example, electron microscopy studies have suggested that the components that distinguish between nodal regions and internodes play a pivotal role in the behavior of macrophages that initiate myelin phagocytosis in the demyelinating form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). Conversely, some patients previously diagnosed with CIDP were found to possess distinctive mechanisms initiated by autoantibodies against paranodal junction proteins such as neurofascin 155 leading to the emergence of the concept of autoimmune nodopathy. In vasculitis, the roles of neutrophils in antineutrophil cytoplasmic antibody-associated vasculitis, eosinophils in eosinophilic granulomatosis with polyangiitis, and complements in nonsystemic vasculitic neuropathy in tissue damage have also been demonstrated when viewed from a modern perspective. Furthermore, mechanisms attributable to predominant small-fiber loss in hereditary transthyretin amyloidosis have been clarified at an ultrastructural level.

Vasculitic neuropathy: Therapeutic progress and prospects

AbstractVasculitic neuropathy has a broad range of etiologies, and roughly comprises nonsystemic vasculitic neuropathy and neuropathies accompanied by antineutrophil cytoplasmic antibody‐associated vasculitis (AAV). Recent morphological analyses of sural nerve specimens from patients with vasculitic neuropathy showed some distinct pathogeneses within vasculitic neuropathy. Several randomized, controlled studies and updated practice guidelines cover immunotherapies for AAV, whereas there is a paucity of evidence for vasculitic neuropathy, including neuropathies associated with AAV. Corticosteroids have been the mainstay of immunotherapy for vasculitic neuropathy, and cyclophosphamide is indispensable for refractory cases. Recent AAV guidelines are shifting their recommendations toward minimizing the harm caused by corticosteroids and cyclophosphamide with a reduced‐dose corticosteroid regimen and the recent advent of various optional drugs, especially molecular‐targeted agents. Clinicians expect the efficacy of reduced‐dose corticosteroid regimens and molecular‐targeted agents in treating vasculitic neuropathy to be verified, and clarification of the mechanism of vasculitic neuropathy might lead to the development of the best treatment based on the background pathogenesis of individual cases.

Vasculitic neuropathy-related disability, pain, quality of life, and autonomic symptoms: a survey of 312 patients.

To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis. Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey. Three hundred and twelve patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1-4] vs 0.5 [0-2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1-3] vs 2 [1-2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy). Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis.

Primary perineuritis, a rare but treatable neuropathy: Review of perineurial anatomy, clinicopathological features, and differential diagnosis.

The perineurium surrounds each fascicle in peripheral nerves, forming part of the blood-nerve barrier. We describe its normal anatomy and function. "Perineuritis" refers to both a nonspecific histopathological finding and more specific clinicopathological entity, primary perineuritis (PP). Patients with PP are often assumed to have nonsystemic vasculitic neuropathy until nerve biopsy is performed. We systematically reviewed the literature on PP and developed a differential diagnosis for histopathologically defined perineuritis. We searched PubMed, Embase, Scopus, and Web of Science for "perineuritis." We identified 20 cases (11 M/9F) of PP: progressive, unexplained neuropathy with biopsy showing perineuritis without vasculitis or other known predisposing condition. Patients ranged in age from 18 to 75 (mean 53.7) y and had symptoms 2-24 (median 4.5) mo before diagnosis. Neuropathy was usually sensory-motor (15/20), painful (18/19), multifocal (16/20), and distal-predominant (16/17) with legs more affected than arms. Truncal numbness occurred in 6/17; 10/18 had elevated cerebrospinal fluid (CSF) protein. Electromyography (EMG) and nerve conduction studies (NCS) demonstrated primarily axonal changes. Nerve biopsies showed T-cell-predominant inflammation, widening, and fibrosis of perineurium; infiltrates in epineurium in 10/20 and endoneurium in 7/20; and non-uniform axonal degeneration. Six had epithelioid cells. 19/20 received corticosteroids, 8 with additional immunomodulators; 18/19 improved. Two patients did not respond to intravenous immunoglobulin (IVIg). At final follow-up, 13/16 patients had mild and 2/16 moderate disability; 1/16 died. Secondary causes of perineuritis include leprosy, vasculitis, neurosarcoidosis, neuroborreliosis, neurolymphomatosis, toxic oil syndrome, eosinophilia-myalgia syndrome, and rarer conditions. PP appears to be an immune-mediated, corticosteroid-responsive disorder. It mimics nonsystemic vasculitic neuropathy. Cases with epithelioid cells might represent peripheral nervous system (PNS)-restricted forms of sarcoidosis.

Subclinical motor involvement in non-systemic vasculitic neuropathy determined by the motor unit number estimation method MScanFit.

Non-systemic vasculitic neuropathy (NSVN) is characterized by a predominant lower-limb involvement in many patients. Motor unit changes in upper extremity muscles have not been investigated in this subgroup, but might be of interest to improve the understanding of the multifocal nature of the disease and counseling of patients on potential future symptoms. We aimed to investigate subclinical motor involvement in upper extremity muscles of patients with lower-limb predominant NSVN using the new motor unit number estimation (MUNE) method MScanFit. In this single center cross-sectional study, 14 patients with biopsy-proven NSVN, with no clinical signs of upper extremity motor involvement, were investigated and compared to 14 age-matched healthy controls. All participants were assessed clinically and by the MUNE method MScanFit to the abductor pollicis brevis muscle. The number of motor units and peak CMAP-amplitudes were significantly reduced in patients with NSVN (p=0.003; p=0.004). Absolute median motor unit amplitudes and CMAP-discontinuities were not significantly different (p=0.246; p=0.1). CMAP-discontinuities were not significantly correlated with motor unit loss (p=0.15, Rho=0.4). The number of motor units did not correlate with clinical scores (p=0.77, Rho 0.082). Both MUNE and CMAP-amplitudes showed motor involvement in upper extremity muscles in lower-limb predominant NSVN. Overall, there was no evidence of significant reinnervation. Investigations of the abductor pollicis brevis muscle did not correlate with the overall functional disability of the patients.

Vasculitis presenting as carpal tunnel syndrome: a case report

BackgroundCarpal tunnel syndrome is the most common focal mononeuropathy which presents with pain in the wrist and hand, paresthesia, loss of sensation in the distribution of the median nerve, and in more severe cases, weakness and atrophy of the thenar muscles. Meanwhile, carpal tunnel syndrome can present as an initial manifestation of underlying systemic vasculitis disorder and result in severe physical disabilities.Case presentationA 27-year-old Iranian man was referred to our electrodiagnosis center with a clinical diagnosis of carpal tunnel syndrome in April 2020. Surgical intervention had been taken into account for him because of unsuccessful conservative therapies. On admission, thenar eminence was reduced. Electrodiagnostic findings were not compatible with median nerve entrapment at the wrist. All sensory modalities in the distribution of the right median nerve were decreased. Additionally, a mild increase in erythrocyte sedimentation rate was noted in laboratory tests. Because of the high vasculitis suspicion, we recommended the nerve biopsy and/or starting a high-dose corticosteroid. However, the surgery release was performed. After 6 months, the patient was referred for progressive weakness and numbness in the upper and lower limbs. After documentation of vasculitis neuropathy by biopsy, a diagnosis of non-systemic vasculitic neuropathy was confirmed. A rehabilitation program started immediately. Rehabilitation led to gradual improvement and recovery of function and muscle strength, and no complications remained, except mild leg paralysis.ConclusionsPhysicians should be suspicious of the median nerve vasculitis mononeuropathy in a patient with carpal tunnel syndrome-like symptoms. Median nerve vasculitis mononeuropathy as an initial presenting feature of vasculitis neuropathy can further result in severe physical impairments and disabilities.

Single-center experience of induction therapy in non-systemic vasculitic neuropathy

BackgroundNo controlled studies for non-systemic vasculitic neuropathy treatment exist (NSVN). We compared the treatment response to induction therapy commonly used in clinical practice in NSVN.MethodsIn this retrospective single-center study, 43 patients with biopsy-proven NSVN were analyzed. Patients were subdivided into groups depending on their initial treatment. Relapse rates, changes of motor and sensory symptoms, adverse events, predictors of relapses, and second-line treatment were compared.ResultsInitial treatment regimens were corticosteroid monotherapy, cyclophosphamide monotherapy, pulsed corticosteroid therapy, and combination therapy. Discontinuation due to adverse events occurred in 6 of 43 patients. Clinical data did not differ between treatment groups. Within 12 months, 24.3% of patients relapsed. The median time to relapse was 4 (1.5, 6) months. No relapse occurred in the combination therapy group. However, there was no statistically significant difference in relapse-free survival between treatment groups (p = 0.58). Neither clinical data nor biopsy analysis predicted relapses sufficiently. As a second-line treatment, cyclophosphamide as mono- or combination therapy was used (7 of 9 patients) most frequently. One patient was treated with methotrexate, and one with IVIG.ConclusionsInduction therapy used in clinical practice is effective and mainly well-tolerated in NSVN. Our data do not support an overall advantage of cyclophosphamide over corticosteroid monotherapy. Controlled trials comparing the effectiveness of induction and maintenance therapy in NSVN are warranted.

Early ultrastructural lesions of anti-neutrophil cytoplasmic antibody- versus complement-associated vasculitis.

This study aims to describe electron microscopic findings of vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) and complement. Sural nerve biopsy specimens were obtained from 10 patients with microscopic polyangiitis (MPA), a representative ANCA-associated vasculitis, and six patients with nonsystemic vasculitic neuropathy (NSVN), who were negative for ANCA but positive for complement deposition. In patients with MPA, attachment of neutrophils to epineurial vascular endothelial cells, migration of neutrophils to the extravascular space via the penetration of the endothelial layer, and release of neutrophil components to the extracellular space were observed. Such neutrophil-associated lesions were not observed in patients with NSVN. Nonetheless, morphological changes in epineurial vascular endothelial cells, such as increases in cytoplasmic organelles and cytoplasmic protrusions into the vascular lumen, were observed in patients with NSVN. Since these findings were observed where light microscopy-based findings suggestive of vasculitis (e.g., the disruption of vascular structures and fibrinoid necrosis) were absent, they were considered early lesions that preceded the formation of the so-called necrotizing vasculitis. In conclusion, this study enabled the visualization of distinctive early ultrastructural lesions associated with ANCA and complement. Further studies are needed to elucidate the molecular basis of the induction of these fine structural changes, which will contribute to the development of targeted therapies based on specific mechanisms of vasculitis.

099 High relapse rate with steroid monotherapy in non-systemic vasculitic neuropathy

IntroductionHistorically, single tissue vasculitis has been managed with steroid monotherapy. Recent data from large longitudinal databases on systemic vasculitis suggest Non-Systemic Vasculitic Neuropathy (NSVN) has higher rates of relapse, recommending that more aggressive immunotherapy is employed.AimTo investigate the relapse rate in NSVN in response to steroid monotherapy.MethodsA retrospective case note review of clinically and/or pathologically defined cases of (Systemic Vasculitic Neuropathy) SVN and NSVN in two London specialist peripheral nerve centres, between 2005- 2012 and 2015 - 2019.Results32 cases of SVN and 34 cases of NSVN were identified. In each group 14 individuals were treated first-line with steroid monotherapy, and 8 with cyclophosphamide. 8 SVN and 9 NSVN cases received steroids plus azathioprine. 15/32 SVN and 13/34 NSVN relapsed after first-line therapy (10/14 and 9/14 on steroid monotherapy, 3/8 and 3/9 on steroids and azathioprine, 2/8 and 1/8 on cyclophosphamide). 10 individuals stabilised with the addition of azathioprine, 13 with cyclophosphamide and 4 with Rituximab.ConclusionThis representative case series suggests that steroid monotherapy is inadequate in the treatment of NSVN and supports an approach akin to that recommended in SVN, even if nerve is the only tissue clinically involved.e.bunting@nhs.net

A study correlating nerve biopsy with clinical diagnosis and its impact on improving management in peripheral neuropathies

BackgroundThis study attempts to evaluate the utility of nerve biopsy in complementing or redirecting clinical diagnosis. Several factors determine the diagnostic utility of nerve biopsy, the most important being pre-biopsy diagnosis, with higher diagnostic yield reported in asymmetric and multi-focal neuropathies. MethodsThis retrospective study was conducted at a tertiary care hospital in South India, wherein, patients with a clinical and electrophysiological diagnosis of peripheral neuropathy who underwent nerve biopsy between Jan 2012- Dec 2016 were reviewed. ResultsA total of 112 nerve biopsies were performed at our Institute during the study period, of which, 84 had adequate information for review and inclusion in the study. In a majority (75) Sural nerve was biopsied, followed by combined superficial peroneal nerve and peroneus tertius muscle biopsy (5).Nerve biopsy diagnosis was concordant with and helped confirm the clinical diagnosis in 43/84 (51%) cases, which included vasculitic neuropathy (20), CIDP (16), leprous neuropathy (6). In10/84 (12%) patients, the nerve biopsy diagnosis was discordant with the clinical diagnosis and helped in redirecting management. This included vasculitic and diabetic neuropathy (2 each), Charcot Marie Tooth Disease (3), and leprous neuropathy (3). In 31/85 (37%) cases with no clinically evident etiological diagnosis, nerve biopsy proved useful in establishing diagnosis in 16/31 (51%) cases aiding patient management. This included Non-systemic vasculitic neuropathy (7), leprous neuropathy (3), diabetic neuropathy (2), and Giant axonal neuropathy (1). ConclusionNerve biopsy remains a valuable tool in complementing or redirecting the clinical diagnosis, and improving the therapeutic outcomes in peripheral neuropathies. It should be done upfront in clinically idiopathic neuropathies, and early at follow up in treatment refractory neuropathies.

Vasculitic Peripheral Neuropathy, Differences Between Systemic and Non-Systemic Etiologies: A Case Series and Biopsy Report.

Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. Twenty-five patients with VPN were included (SVN, n = 10; NSVN, n = 15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, p = 0.009). Erythrocyte sedimentation rate (ESR) values over 20 mm/h were significantly more common in SVN patients (100% vs. 60%, p = 0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; p = 0.03), with a higher proportion of definite VPN cases (92 vs 46%; p = 0.04). Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.

Nonsystemic vasculitic neuropathy

A 21-year-old female born of nonconsanguineous marriage presented with gradually progressive quadriplegia for 3 years. Weakness was distal more than proximal, with wasting. She also had moderate pain in extremities. She had significant weight loss. Clinically, she had lower motor neuron flaccid quadriplegia with absent deep tendon jerks. Sensations of touch and pain were diminished in bilateral feet till ankle joints. Peripheral nerves were not thickened. Nerve conduction study was suggestive of pure axonal sensorimotor polyneuropathy. All routine hematological and biochemical parameters, erythrocyte sedimentation rate, antinuclear antibodies, and antinuclear cytoplasmic antibodies were negative. Cerebrospinal fluid showed no cells, normal sugar, and raised proteins. Biopsy of sural nerve was suggestive of vasculitic neuropathy. This was a case of nonsystemic vasculitic neuropathy that responded to steroids.

Peripheral nervous system lesion in systemic vasculitis - issues of diagnosis and treatment

Vasculitis is a clinically diverse group of diseases with histopathological signs of blood vessel inflammation, which contributes to vascular damage and ischemic damage to the affected tissues. Vasculitic neuropathy is a common complication of the primary systemic vasculitides, such as polyartertis nodosa and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic diseases of the connective tissue - systemic lupus erythematosus and Sjogren syndrome, vasculitis associated with infection, most often viral hepatitis C and B and non - systemic vasculitis neuropathy. Vessels of medium and small caliber are involved in the pathological process in these diseases. With all vasculitis, except for those caused by the direct effect of the infectious trigger on the blood vessel walls, the main pathogenetic mechanism is an autoimmune process with the development of vasa nervorum vasculitis - small arteries and vessels that supply peripheral nerves, and the outcome - nerve ischemia. The classic clinical presentation is an acute or subacute painful multifocal neuropathy that has a predilection for the lower extremities, affects two or more named nerves, and progresses in a step wise manner. However, vasculitic neuropathy can manifest in a variety of ways, including asymmetric polyneuropathies and distal symmetric sensory neuropathies, and it also can be slowly progressive, particularly in cases of nonsystemic vasculitic neuropathy (NSVN), a form of vasculitis that clinically remains restricted to peripheral nerves. Nerve biopsy can help establish the diagnosis of a systemic vasculitis, particularly when other organ involvement is not clinically apparent, and is required for diagnosis of NSVN. Neuropathy due to systemic vasculitis should be treated in accordance with the recommendations for the treatment of the underlying disease. In NSVH, the main medicine of choice are glucocrticoids, and in severe/progressive cases, pulse therapy with cyclophosphamide.

Diagnostic Value of Sural Nerve Biopsy: Retrospective Analysis of Clinical Cases From 1981 to 2017.

Nerve biopsy represents the conclusive step in the diagnostic work-up of peripheral neuropathies, and its diagnostic yield is still debated. The aim of this study is to consider the impact of nerve biopsy on reaching a useful diagnosis in different peripheral neuropathies and its changing over time. We retrospectively analyzed 1,179 sural nerve biopsies performed in the period 1981–2017 at Neurological Clinic of Policlinico San Martino (Genoa). We relied on medical records and collected both clinical and pathological data in a database. Biopsy provided univocal diagnoses in 53% of cases (with an increase over time), multiple diagnostic options in 14%, while diagnosis was undetermined in 33% (undetermined reports decreased during the years). In 57% of patients, the pre-biopsy suspicion was confirmed, while in 43% sural biopsy modified the clinical diagnosis. The highest yield was in axonal neuropathies (29% undetermined reports vs. 40% in demyelinating and 48% in mixed neuropathies). In 68% of patients with vasculitic neuropathy, this etiology was already suspected, whereas in 32% nerve biopsy modified the clinical diagnosis. During the years, the number of annually performed biopsies decreased significantly (p = 0.007), with an increase in the mean age of patients (p < 0.0001). The percentage of hereditary neuropathies had a significant decrease (p = 0.016), while the rate of vasculitic and chronic inflammatory neuropathies increased (p < 0.0001). This is the largest Italian study addressing the yield of sural nerve biopsy. During the years, we observed a progressive refinement of the indication of this procedure, which confirms its utility for interstitial neuropathies, particularly if non-systemic vasculitic neuropathy is suspected.

Update on classification, epidemiology, clinical phenotype and imaging of the nonsystemic vasculitic neuropathies.

Single-organ vasculitis of the peripheral nervous system (PNS) is often designated nonsystemic vasculitic neuropathy (NSVN). Several variants or subtypes have been distinguished, including migratory sensory neuropathy, postsurgical inflammatory neuropathy, diabetic radiculoplexus neuropathies, skin-nerve vasculitides, and, arguably, neuralgic amyotrophy. NSVN often presents as nondiabetic lumbosacral radiculoplexus neuropathy (LRPN). This review updates classification, clinical features, epidemiology, and imaging of these disorders. A recent study showed the annual incidence of LRPN in Olmstead County, Minnesota to be 4.16/100 000:2.79/100 000 diabetic and 1.27/100 000 nondiabetic. This study was the first to determine the incidence or prevalence of any vasculitic neuropathy. In NSVN, ultrasonography shows multifocal enlargement of proximal and distal nerves. In neuralgic amyotrophy, MRI and ultrasound reveal multifocal enlargements and focal constrictions in nerves derived from the brachial plexus. Histopathology of these chronic lesions shows inflammation and rare vasculitis. Diffusion tensor imaging of tibial nerves in NSVN revealed decreased fractional anisotropy in one study. Single-organ PNS vasculitides are the most common inflammatory neuropathies. Neuralgic amyotrophy might result from PNS vasculitis, but further study is necessary. The usefulness of focal nerve enlargements or constrictions in understanding pathological mechanisms, directing biopsies, and monitoring disease activity in NSVN should be further investigated.

Vasculitic Neuropathies.

Vasculitic neuropathies are disorders that result from inflammation in the peripheral nerves' vascular supply, resulting in ischemic injury. These disorders may be a result of systemic inflammation or may be confined to the peripheral nervous system. Causative etiologies include primary systemic vasculitis, vasculitis secondary to other conditions such as primary connective tissue disorders, infectious, paraneoplastic, and drug-induced conditions, and nonsystemic vasculitic neuropathy. Early recognition and treatment of these conditions is imperative to prevent substantial morbidity and mortality. The goal of this review is to provide an organization of the vasculitic neuropathies and an overview of principles of diagnosis and treatment for the clinical neurologist.

MRI detects peripheral nerve and adjacent muscle pathology in non-systemic vasculitic neuropathy (NSVN).

Diagnosis and disease monitoring of non-systemic vasculitic neuropathy (NSVN) are based on electrophysiological and clinical measures. However, these methods are insensitive to detect subtle differences of axonal injury. We here assessed the utility of a multiparametric MRI protocol to quantify axonal injury and neurogenic muscle damage in NSVN. Ten NSVN patients and ten age-matched controls were investigated in this single-center prospective study. All participants were assessed by diffusion tensor imaging (DTI) of the tibial nerve and multiecho Dixon MRI of soleus and gastrocnemius muscles. These data were correlated with clinical and electrophysiological data. DTI scans of the tibial nerves of patients with NSVN showed significantly lower mean fractional anisotropy (FA) values (0.32 ± 0.02) compared to healthy controls (0.42 ± 0.01). FA values of NSVN patients correlated negatively with clinical measures of pain. Multiecho Dixon MRI scans revealed significantly higher intramuscular fat fractions in the soleus muscle (19.86 ± 6.18% vs. 5.86 ± 0.74%, p = 0.0015) and gastrocnemius muscle (26.09 ± 6.21% vs. 3.59 ± 0.82%, p = 0.0002) in NSVN patients compared to healthy controls. Our data provide a proof of concept that MRI can render information about nerve integrity and muscle pathology in NSVN. Further studies are warranted to evaluate DTI and multiecho Dixon MRI as surrogate markers in NSVN.