RT Journal Article
SR Electronic
T1 Contactin-1 autoimmunity
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e771
DO 10.1212/NXI.0000000000000771
VO 7
IS 4
A1 Dubey, Divyanshu
A1 Honorat, Josephe A.
A1 Shelly, Shahar
A1 Klein, Christopher J.
A1 Komorowski, Lars
A1 Mills, John R.
A1 Brakopp, Stefanie
A1 Probst, Christian
A1 Lennon, Vanda A.
A1 Pittock, Sean J.
A1 McKeon, Andrew
YR 2020
UL http://nn.neurology.org/content/7/4/e771.abstract
AB Objective To determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity.Methods Archived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed.Results We identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonged distal latencies) without conduction block. Markedly elevated CSF protein (median 222 mg/dL, range 69–960 mg/dL), thickening/gadolinium enhancement of nerve roots (4/5), and subperineural edema on nerve biopsy (4/4) were other characteristic features. Three cases were diagnosed with paraneoplastic demyelinating neuropathies (thymoma, n = 1; breast cancer, n = 1; plasmacytoma, n = 1). Four of the 9 patients treated with IV immunoglobulin demonstrated initial clinical improvement, but the favorable response was sustained in only 1 case (median follow-up, 60 months). Sustained clinical stabilization or improvement was observed among 3 of the 6 cases in whom second-line therapies (rituximab, cyclophosphamide, and azathioprine) were used.Conclusion Contactin-1 IgG has a distinct sensory predominant presentation commonly associated with neuropathic pain, with demyelinating changes on electrophysiologic studies. A paraneoplastic cause should be considered. Testing of contactin-1 IgG among cases with similar presentations may guide immunotherapy selection, especially second-line immunotherapy consideration.AIDP=acute inflammatory demyelinating polyradiculoneuropathy; CIDP=chronic inflammatory demyelinating polyradiculoneuropathy; CISP=chronic immune sensory polyradiculopathy; CN=cranial nerve; IFA=immunofluorescence assay; Ig=immunoglobulin; IVIG=intravenous immunoglobulin; NCS=nerve conduction study; SSEP=somatosensory evoked potential