PT  - JOURNAL ARTICLE
AU  - Dubey, Divyanshu
AU  - Honorat, Josephe A.
AU  - Shelly, Shahar
AU  - Klein, Christopher J.
AU  - Komorowski, Lars
AU  - Mills, John R.
AU  - Brakopp, Stefanie
AU  - Probst, Christian
AU  - Lennon, Vanda A.
AU  - Pittock, Sean J.
AU  - McKeon, Andrew
TI  - Contactin-1 autoimmunity
AID  - 10.1212/NXI.0000000000000771
DP  - 2020 Jul 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e771
VI  - 7
IP  - 4
4099  - http://nn.neurology.org/content/7/4/e771.short
4100  - http://nn.neurology.org/content/7/4/e771.full
SO  - Neurol Neuroimmunol Neuroinflamm2020 Jul 01; 7
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