Diagnostic value of sural nerve biopsy in patients with suspected Borrelia neuropathy

Abstract

Peripheral neuropathy is a recognized but incompletely understood manifestation of borreliosis. As the pathology of this neuropathy has been described only in small case series, the value of nerve biopsy findings for the pathologic diagnosis of Borrelia-associated neuropathy is unclear. We collected and investigated 21 patients with peripheral neuropathy and with typical clinical and serologic signs of neuroborreliosis [Borrelia neuropathy (BN)]. Standard histology and immunohistochemistry were performed on sural nerve biopsies using antibodies to CD4, CD68 and membrane attack complex C5b-9, intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6. Nine patients with idiopathic vasculitic neuropathy (VN) and 14 with idiopathic axonal neuropathy (AN) served as disease controls. In BN, the characteristic histology was that of an AN with transmural or perivascular lymphocytic infiltration of nerve vessels. In BN, but less in VN and AN, perineurial thickening and neovascularization were observed. For BN but not for VN, this thickening correlated with increased perineurial immunoreactivity (IR) to TNF-alpha, C5b-9, and ICAM-1. In comparison to AN, both BN and VN displayed increased perineurial T-cell infiltration and human leukocyte antigen (HLA)-DR3-IR. In the endoneurium, cytokine (IL-1beta, IL-6, TNF-alpha), HLA-DR3, and ICAM-1 expression was more pronounced in VN but not in BN. The neuropathy in patients with neuroborreliosis resembles idiopathic VN but shows some distinctive features. None of the findings of this study are disease specific but as a pattern may help support the diagnosis of inflammatory neuropathy in patients with serological evidence for Borrelia infection.

Peripheral Nerve Society Guideline on processing and evaluation of nerve biopsies

“…In the diagnosis of paraneoplastic neuropathies, in accordance with an European Federation of Neurological Societies (EFNS) task force ( Vedeler et al, 2006 ) , nerve biopsy is usually not necessary, but might sometimes be helpful in the detection of vasculitis. For borrelia‐associated neuropathy, there is class IV evidence that nerve biopsy may be helpful if clinical and serological evidence is insufficient ( Vallat et al, 1987 ; Meier et al, 1989 ; Schäfers et al, 2008 ) . Whether nerve biopsy is useful in hepatitis‐associated neuropathy remains unclear.…”

Processing of nerve biopsies: A practical guide for neuropathologists

“…A characteristic pattern of perineurial TNF-α, C5b-9, and ICAM-1 expression has been found in sural nerve biopsies of borreliosis patients [36]. …”

Infectious and tropical neuropathies

“…In our experience, demyelinating lesions or infiltrating inflammatory cells with dissociation of myelin lamellae like that seen in GBS did not occur, and there was no necrosis of vessel walls [19]. Schafers et al have studied various types of cytokines in the nerves of several patients [18].…”