Abstract
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 clinicopatho-logical 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 histopatho-logically defined perineuritis. We searched PubMed, Embase, Scopus, and Web of Science for “perineuritis.” We identified 20 cases (11 M/9F) of PP: progressive, unex-plained 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 biop-sies 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 addi-tional immunomodulators; 18/19 improved. Two patients did not respond to intrave-nous 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, vas-culitis, 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 neu-ropathy. Cases with epithelioid cells might represent peripheral nervous system (PNS)-restricted forms of sarcoidosis.