Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis

DOI: 10.3410/f.727761879.793534379
The authors of this article discuss a novel finding of episodic ataxia occurring in a patient with anti-CASPR2-mediated encephalitis. They also utilize a retrospective chart review to exam the occurrence of episodic ataxia in patients with documented anti-CASPR2-mediated neurological disease.

The case involves a 61-year-old male who presented with a generalized tonic-clonic seizure preceded by several days of cognitive deficits and emotional lability. The patient’s cognitive difficulties persisted, and about one month following onset of seizures he developed episodes of episodic dysarthria, dysmetria, and ataxia, often associated with standing upright or with emotion. Evaluation demonstrated serum and cerebrospinal fluid anti-CASPR2 antibodies and did not disclose any other alternative cause for his episodic ataxia, although he did undergo genetic testing, which demonstrated a polymorphism of the CACNA1A gene. The patient was treated with three days of daily methylprednisolone followed by cyclophosphamide every six months with immediate improvement of ataxic episodes, and improvement of cognitive deficits and seizures at a later point in time.

The retrospective chart review assessed a cohort of 37 separate cases of serum or cerebrospinal fluid (CSF) anti-CASPR2-mediated neurological disease. They identified five patients with transient cerebellar symptoms. All five had anti-CASPR2 antibodies in both serum and CSF, and presented with encephalitis. Symptoms experienced included episodes of ataxia, dysarthria, dysmetria, and/or nystagmus. Cerebellar symptoms began at the time of or following presentation, although one patient reported symptoms seven months prior. Four patients responded to various immunotherapies, with one patient spontaneously improving.

The authors demonstrate an important novel finding of episodic ataxia in the setting of anti-CASPR2-mediated autoimmune encephalopathy. In all but one patient described in this article, intermittent, stereotyped cerebellar symptoms occurred at the time of other presenting symptoms although one patient did have symptoms preceding presentation. All the patients responded positively to immunotherapy. Based on these findings, clinicians should strongly consider testing CASPR2 in patients presenting with episodic ataxia in later decades of life, especially in the setting of cognitive deficits and/or emotional lability. As the authors also discuss, the patient in the case had a polymorphism in the CACNA1A gene, which may have predisposed him to being unable to compensate for the cerebellar symptoms secondary to the CASP2-antibody. While impossible to assess if this was clinically significant or not, further prospective genetic testing in patients with CASPR2-antibody-mediated encephalitis presenting with episodic ataxia may shed light onto this question.

Thanks for sharing! This is the first study I’ve seen where EA is associated with autoimmunity or any antibody. Interesting to know. I have not read the whole article yet but I wonder what is the rate of progression and frequency. I’d imagine it may be more rapid than the pure channelopathy type of EA without antibody. I’ll definitely spare some time to read it through. Thanks again :blush: