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Systematic review of the clinical spectrum of CASPR2 antibody syndrome

  • Original Communication
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Abstract

Background

Contactin-associated protein-like 2 (CASPR2) autoantibody disease has a variable clinical phenotype. We present a case report and performed a systematic review of the literature to summarize: (1) the clinical phenotype of patients with CASPR2 antibodies, (2) the findings in neurological investigations, and (3) the associated neuroimaging findings.

Methods

A chart review was performed for the case report. A systematic review of the medical literature was performed from first available to June 13, 2018. Abstracts were screened, and full-text peer-reviewed publications for novel patients with CASPR2 positivity in serum or cerebrospinal fluid (CSF) were included. Selected publications were reviewed, and relevant information was collated. Data were analyzed to determine overall frequency for demographic information, clinical presentations, and investigation findings.

Results

Our patient was a previously healthy 61-year-old male with both serum and CSF CASPR2 antibodies who presented with limbic encephalitis and refractory epilepsy. He was successfully treated with immunosuppression. For our systematic review, we identified 667 patients from 106 studies. Sixty-nine percent were male. Median age was 54 years (IQR 39–65.5). Median disease duration was 12 months (IQR 5.6–20). Reported overall clinical syndromes were: autoimmune encephalitis [69/134 (51.5%)], limbic encephalitis [106/274 (38.7%)], peripheral nerve hyperexcitability [72/191 (37.7%)], Morvan syndrome [57/251 (22.7%)], and cerebellar syndrome [24/163 (14.7%)]. Patients had positive serum [642/642 (100%)] and CSF [87/173 (50.3%)] CASPR2 antibodies. MRI was reported as abnormal in 159/299 patients (53.1%), and the most common abnormalities were encephalitis or T2 hyperintensities in the medial temporal lobes, or hippocampal atrophy, mesial temporal sclerosis, or hippocampal sclerosis. FDG-PET was abnormal in 30/35 patients (85.7%), and the most common abnormality was temporomesial hypometabolism. The most commonly associated condition was myasthenia gravis (38 cases). Thymoma occurred in 76/348 patients (21.8%). Non-thymoma malignancies were uncommon [42/397 (10.6%)].

Conclusions

Most patients have autoimmune or limbic encephalitis and corresponding abnormalities on neuroimaging. Other presentations include peripheral nerve hyperexcitability or Morvan syndromes, cerebellar syndromes, behavioral and cognitive changes, and more rarely movement disorders. The most commonly associated malignancy was thymoma and suggests a role for thymoma screening in CASPR2-related diseases.

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Abbreviations

CASPR2:

Contactin-associated protein-like 2

CIDP:

Chronic inflammatory demyelinating polyneuropathy

CJD:

Creutzfeldt–Jakob disease

CSF:

Cerebrospinal fluid

CT:

Computed tomography

C/T/L:

Cervical, thoracic, lumbar

EEG:

Electroencephalogram

EMG:

Electromyography

FDG-PET:

Fluorodeoxyglucose positron emission tomography

IQR:

Interquartile range

IVIG:

Intravenous immunoglobulin

LGI1:

Leucine-rich gene, glioma inactivated

MoCA:

Montreal Cognitive Assessment

MRI:

Magnetic resonance imaging

NMDA:

N-methyl-D-aspartate

NOS:

Not otherwise specified

SIADH:

Syndrome of inappropriate antidiuretic hormone secretion

VGKC:

Voltage-gated potassium channel

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Acknowledgements

The authors would like to thank Dr. Christine P. Molnar for assistance in acquiring and interpreting the FDG-PET images and Ms Helen Lee Robertson for her assistance with the search strategy for the systematic literature review.

Funding

This was not a funded study.

Author information

Authors and Affiliations

  1. Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, HMRB 155, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada

    Matthew Boyko, Ka Loong Kelvin Au, Colin Casault, Paula de Robles & Gerald Pfeffer

  2. Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

    Gerald Pfeffer

  3. Alberta Child Health Research Institute, University of Calgary, Calgary, Canada

    Gerald Pfeffer

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Contributions

M.B. analyzed clinical data, performed the systematic literature review, and drafted the manuscript. K.K.A. analyzed clinical data, performed the systematic literature review, and edited the manuscript for intellectual content. C.C. analyzed clinical data and edited the manuscript for intellectual content. P.d.R. analyzed clinical data and edited the manuscript for intellectual content. G.P. analyzed clinical data, edited the manuscript for intellectual content, and supervised the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gerald Pfeffer.

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Conflicts of interest

All authors declare there are no competing interests with this study.

Ethics approval and consent to participate

Institutional research ethics board approval was not obtained for this study.

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The participant provided written informed consent for publication of this case report.

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Boyko, M., Au, K.L.K., Casault, C. et al. Systematic review of the clinical spectrum of CASPR2 antibody syndrome. J Neurol 267, 1137–1146 (2020). https://doi.org/10.1007/s00415-019-09686-2

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  • DOI: https://doi.org/10.1007/s00415-019-09686-2

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