Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease

Abstract

Background: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. Aims: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. Methods: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. Results: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. Conclusion: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.

Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis

“…As is well known, the detection of anti-CASPR2 antibodies in serum or CSF is crucial for the definite diagnosis of anti-CASPR2 antibody-associated disorders ( 3 ), whereas in recent years, the extensive expansion of clinical spectrum has made it more difficult to differentiate this disease from other mimics, in particular when anti-CASPR2 antibodies cannot be tested or the results have not been obtained ( 4 , 15 ). Similarly, both cases in this study mimicked progressive brainstem infarction with severe neurological manifestations, rather than presented with characteristic limbic encephalitis or refractory seizures.…”

“…Robust imaging evidence reveals that the medial temporal lobe is the most vulnerable CNS region associated with anti-CASPR2 antibodies ( 4 , 15 , 17 , 18 ). In a review enrolling 667 patients with anti-CASPR2 antibody-associated disorders, 299 received MRI scans and abnormal CNS lesions were reported in 159 cases.…”

“…At present, there are no standard recommendations or consensus-based practice guidelines for the treatment of anti-CASPR2 antibody-associated autoimmune encephalitis, and available data from large retrospective and observational studies are sparse. However, given the autoimmune participation in this disease entity, early and aggressive therapies focusing on different segments of immune responses have been applied in several studies and good/full or partial responses can be achieved in the majority of patients ( 10 , 15 ). The first-line immunotherapies consist of corticosteroids, IVIg, plasma exchange (PE), or combined treatment.…”

“…The first-line immunotherapies consist of corticosteroids, IVIg, plasma exchange (PE), or combined treatment. Other second-line immunosuppressive agents such as azathioprine, mycophenolate, rituximab, and cyclophosphamide could be considered when no favorable responses to sufficient first-line therapies are obtained ( 3 , 15 ). In this study, one case had full neurologic recovery after corticosteroids (intravenous and oral) plus IVIg were given, whereas the other did not have a favorable response to the first-line therapies including corticosteroids and IVIg.…”

Pathology of Initial Axon Segments in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders

“…Caspr2 is found in both the CNS and PNS, expressed in juxtaparanodes and some isolated paranodal loops. It has been postulated that its role in stabilizing potassium channels and thus maintaining the resting potential of the membrane may be of clinical importance in several disorders, such as autism or Parkinsonian-ataxia spectrum [ 39 , 40 , 41 , 42 , 43 ]. The extracellular region of Caspr2 is a mosaic of domains, including laminin G, EGF-like cysteine-rich domain, and fibrinogen domains.…”