Vasculitis and the peripheral nervous system.

Peripheral neuropathy is a common feature of systemic vasculitis and can also occur when vessel wall inflammation is confined to the vasa nervorum, as a tissue-specific condition-non-systemic vasculitic neuropathy (NSVN). Typically, the clinical picture in both systemic and non-systemic cases is of a lower limb predominant, distal, asymmetric or multifocal neuropathy, which is painful and subacute in onset. For NSVN, nerve biopsy is required to make the diagnosis, and nerve biopsy also has a role when vasculitic neuropathy is suspected and a systemic process has not yet declared itself. Early recognition of the disorder is important, because it is treatable, and without treatment potentially disabling, or even lethal if part of an undiagnosed systemic process. Treatment is generally with combination therapy (glucocorticoid plus other immunosuppressant), after which motor and sensory recovery are likely to occur, albeit slowly, but the patient may be left with chronic neuropathic pain.

Lymphocyte antigens targetable by monoclonal antibodies in non-systemic vasculitic neuropathy.

OBJECTIVE: To identify the most relevant antigens for monoclonal antibodies in lymphocytic infiltrates in non-systemic vasculitic neuropathy (NSVN). BACKGROUND: Current immunosuppressive treatment for NSVN is insufficient. Monoclonal antibodies might be a treatment option, but the expression profile for targetable antigens on lymphocytic infiltrates in NSVN is unknown. METHODS: Sural nerve biopsies from a cohort of patients with NSVN were immunohistochemically studied for the expression of potential candidate antigens in perivascular and intramural lymphocytic infiltrates and correlated with neurological and electrophysiological parameters. 20 patients with treatment naïve NSVN and 5 patients with idiopathic axonal neuropathy were included. RESULTS: The CD52, BAFF and CD49d antigens were expressed in epineurial, perivascular or intramural lymphocytes of all (20/20) patients. CD52 was most prominently expressed in 21.49% of all inflammatory infiltrates. BAFF and CD49d were detected in 11.25% and 10.99% of these lymphocytes, respectively. The CD20, CD25 and CD126 antigens were found less frequently and at low levels only (CD20: 10/20 patients, 5.84% of lymphocytes; CD25: 17/20 patients, 5.22% of lymphocytes; CD126: 3/20 patients, 0.15% of lymphocytes). CONCLUSION: This is the first study in NSVN that identifies antigens expressed by pathogenic lymphocytes, which are potential targets for future monoclonal antibody treatment. Our data suggest that NSVN is amenable to monoclonal antibodies and, moreover, that targeting CD52 may be particularly promising. Our results strongly warrant future clinical trials in NSVN with monoclonal antibodies.

[Peripheral neuropathies during systemic diseases: Part II (vasculitis)]. / Neuropathies périphériques au cours des maladies de système : partie II (vascularites).

Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement…), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.

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

BACKGROUND: 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. OBJECTIVE: This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Non-systemic vasculitic neuropathy: single-center follow-up of 60 patients.

The objective of this study is to report the clinical presentation and long-term outcome of patients with non-systemic vasculitic neuropathy (NSVN) seen at our neuromuscular center. In this retrospective analysis, we assessed medical records of 60 patients with biopsy-proven NSVN (39 men, 21 women; median age: 64 years, 24-80), who were seen at our department between 1999 and 2008 and were followed up until 2014. The initial neurological findings, laboratory and neurophysiological data, treatment regimens, and outcome were analyzed in all patients. NSVN was mostly asymmetric (48/60, 80%), sensorimotor (45/60, 75%), and painful (38/60, 63%), with walking impairment as one major sign (51/60, 85%). No compound action potentials could be recorded in 29/60 (48%) sural nerves (later biopsied side) and in 6/60 (10%) tibial (motor) nerves. Pathology of sural nerve was informative in all cases irrespective of neurophysiological findings and prior immunosuppression. After initial treatment with i.v. methylprednisolone, all patients reported overall improvement. Of the 46 patients who were followed for >1 year, those with mild to moderate affliction were stable with azathioprine (19/46, 41%), while 18/46 (39%) patients were treated with cyclophosphamide and other immunosuppressants due to progression or relapse. At 4 years, 24/46 (52%) patients had either discontinued (n = 21) or had primarily refused immunosuppressive treatment (n = 3) without relapse. Age younger than the group median of 64 years was associated with better outcome. No patient evolved to systemic vasculitis. NSVN is a potentially treatable disorder of the peripheral nervous system.