CASPR2 encephalitis presenting as post-partum psychosis

To the Editor,

Autoimmune encephalitis may present with psychiatric symptoms, and screening for serum neuronal antibodies is now commonly performed in first episode or atypical psychosis. Behavioural disturbance is thought to occur in over 60% of contactin-associated protein-like 2 (CASPR2) cases; however, psychosis at presentation has not been previously reported (Gadoth et al., 2017; Irani et al., 2010; Van Sonderen et al., 2016).

A 28-year-old female, 6 weeks post partum, with no psychiatric or medical history, presented after 7 days of agitation, disorganisation, speech disturbance and insomnia. She was highly anxious, thought disordered and described bizarre delusions, without perceptual phenomena. The pregnancy was planned, with no ante- or post-natal complications. The patient’s sister had died 2 years prior during pregnancy which contributed to the formulation of post-partum psychosis.

Neurological examination, blood tests, urine microscopy and drug screen, magnetic resonance imaging (MRI) brain and cerebrospinal fluid (CSF) assessment were unremarkable. CSF and serum neuronal antibodies, including voltage-gated potassium channel (VGKC) and N-methyl-D-aspartate receptor (NMDAR), were negative.

One day after admission, periods of mutism, grimacing and stereotypy (repetitive finger play) alternated with agitation, impulsivity and rapid, perseverative speech. Treatment with olanzapine, risperidone, lithium and lorazepam was ineffective and electro-convulsive therapy (ECT) commenced at 4 weeks. The development of generalised rigidity and ataxia at 5 weeks prompted concern for neuroleptic malignant syndrome and psychotropics and ECT were ceased. Serum and CSF neuronal antibodies were retested, this time including cell-based assay for leucine-rich glioma-inactivated protein 1 (LGI1) and CASPR2 antibodies. Serum was positive for CASPR2 and negative for VGKC; CSF CASPR2 was negative.

Treatment was initiated with intravenous (IV) immunoglobulin, steroids and plasma exchange. By the third cycle of plasmapheresis, there was complete resolution of psychosis, behavioural disturbance and rigidity. Ataxia resolved at 10 weeks with the addition of rituximab. There was no evidence of malignancy, neuromyotonia or seizures.

The clinical spectrum of disorders associated with CASPR2 antibodies is diverse but the most common presentation is with cognitive deficits, seizures and pain, potentially masked in this case by the severity of behavioural disturbance (Gadoth et al., 2017; Van Sonderen et al., 2016). In addition, the development of further neurologic manifestations, and rapid response to immunotherapy, of otherwise resistant psychiatric symptoms makes it unlikely that the CASPR2 antibodies were incidental. Negative serum VGKC antibodies can be falsely reassuring. Cases with positive CASPR2 and negative VGKC testing have been reported, and where there is a suspicion for limbic encephalitis, clinicians should consider specific antibody testing (Gadoth et al., 2017; Van Sonderen et al., 2016). This case illustrates the expanding phenotype of CASPR2-associated disease and reinforces the importance of diagnostic re-evaluation when new clinical features emerge.