Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease

Abstract

Background: Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs.

Methods: We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers.

Results: In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48 years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031).

Conclusions: PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.

Keywords: Autoimmune encephalitis; ENMG; GFAP; Peripheral neuropathy.

Fig. 1

Diagram of patients with CSF GFAP antibodies and peripheral nervous system involvement. CSF, cerebrospinal fluid; CNS, central nervous system; PNS, peripheral nervous system; ENMG, electroneuromyography. *4 patients presented with both pathological ENMG and cranial nerve involvement

Fig. 2

Venn diagram representing patients’ repartition according to CNS involvement, cranial nerve involvement, and abnormal ENMG. CNS, central nervous system; ENMG, electroneuromyography

Fig. 3

Brain and spinal cord MRI features of patients with CSF GFAP antibodies and PNS involvement. Brain MRI of a patient with glial fibrillary acidic protein (GFAP) antibodies showing brainstem leptomeningeal and acoustic-facial bundle contrast enhancement (A, red arrows). Spinal cord MRI of a patient with GFAP antibodies showing medullar leptomeningeal and root contrast enhancement (B, C, red arrows)