Limbic encephalitis

Did You Know?

• Limbic encephalitis associated with voltage-gated potassium channel antibodies may frequently be non-paraneoplastic.
• A study of 15 cases found raised VGKC-Abs associated with non-paraneoplastic disorders and remission following immunosuppressive treatment.

Diagnosis

Diagnosis of limbic encephalitis is often delayed for weeks because the key test—detection of specific auto-antibodies in cerebrospinal fluid—is not routinely offered by most immunology laboratories. Some rare auto-antibodies, such as anti-NMDAR, have no commercially available assay and can only be measured by a small number of research laboratories worldwide, further prolonging the diagnostic process. Most patients are initially diagnosed with herpes simplex encephalitis, as the two syndromes are clinically indistinguishable; HHV-6 encephalitis also presents identically.

Two sets of diagnostic criteria exist. The older criteria were proposed by Gultekin et al. in 2000, and a revised set by Graus and Saiz in 2005. The main difference between them is whether detection of a paraneoplastic antibody is required for diagnosis. The main antibodies in the paraneoplastic group target Hu, Ma2, CV2, amphiphysin, and Ri; anti-Ma2 encephalitis may be clinically mistaken for Whipple's disease. The main antibodies in the non-paraneoplastic group target NMDAR and the VGKC-complex. Anti-NMDAR encephalitis is strongly associated with benign ovarian tumours, while anti-VGKC-complex encephalitis is most often not tumour-associated.

Patients with NMDAR encephalitis are frequently young women who present with fever, headache, and fatigue, often misdiagnosed as influenza, then progress to severe behavioural disturbance, delusions, and psychosis, sometimes leading to psychiatric admission. The disease advances to catatonia, seizures, loss of consciousness, hypoventilation requiring intubation, orofacial dyskinesia, and autonomic instability. CSF examination typically shows elevated lymphocytes, elevated protein, normal glucose, elevated IgG index, and oligoclonal bands; patients with VGKC antibodies may have a completely normal CSF examination.