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

1) Understand perineurial anatomy and function in a manner relevant to human perineuritis; 2)be able to recognize the clinical, laboratory, and histopathological features of primary perineuritis and implement appropriate therapy; 3) Be able to recognize and implement treatment for the major causes of secondary perineuritis: vasculitic neuropathy, leprous neuropathy, neurosarcoidosis, neuroborreliosis, ad neurolymphomatosis. 

The AANEM is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The AANEM designates this enduring material for a maximum of 1 AMA PRA Category 1 Credits TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity. Credit expires 10/7/2026.

Authors had no conflicts to disclose.

Michael P. Collins MD; Robert D. M. Hadden BM, BCh, FRCP, PhD; Nazima Shahnoor, PhD
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Expires on Oct 07, 2026
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