Antibodies are directed against the NR1 subunit of the NMDA receptor. Clinical manifestations typically include:
CSF may show lymptocytic pleocytosis, elevated protein, positive oligoclonal bands. MRI is abnormal in a third of cases with cortical/subcortical hyperintensities commonly seen. EEG usually shows diffuse slowing and may show extreme delta brush pattern. Diagnosis is supported by identification of NMDA receptor antibody in CSF (serum may be negative). In women the risk of ovarian teratoma is high and this should be excluded.
Antibodies directed against the voltage gated potassium channels bind to other proteins including LGI1 (leucine-rich, glioma-inactivated 1 protein) and CASPR2 (contactin-associated protein 2) resulting in a complex antibody. These antibodies cause limbic encephalitis with the following common features:
CSF findings are usually normal. Neuroimaging may be normal but often shows mesial temporal T2 hyperintensity which is usually asymmetric and does not enhance. EEG often shows frontotemporal or generalized slowing and focal temporal epileptiform discharges. Diagnosis is supported by identification of voltage gated potassium channel antibody in serum (or anti-LGI1 or anti-CASPR2), antibody may not be present in CSF.
Low titers of GAD65 are commonly seen as a marker of thyrogastric autoimmunity and are not concerning for neurological disease. Very high titers (>20 nmol/l in serum) can be associated with variable neurological symptoms including limbic encephalitis. Diagnosis is supported by identification of GAD65 antibody in CSF.
GABA-B receptor antibodies may present with limbic encephalitis and are most commonly found in adults with small cell lung cancer. Diagnosis is supported by identification of GABA-B receptor antibody in serum.
AMPA receptor antibodies may present with limbic encephalitis and are most commonly found in older patients in association with cancers of the thymus, breast or lung. Diagnosis is supported by identification of AMPA receptor antibody in serum. Given the risk of cancer, this should be excluded.
Anti-TPO antibody, present in this disorder, is common in the population. The following criteria are therefore proposed for the clinical diagnosis of steroid-responsive encephalopathy associated with thyroid disease:
Diagnosis is supported by identification of anti-TPO receptor antibody in serum and the exclusion of other etiologies (requiring full testing of serum and CSF, including searches for other anti-neuronal antibodies).
An association between epilepsy and celiac disease has been debated however has not been convincingly established in more careful studies. Celiac disease, epilepsy and occipital calcifications is a rare condition with the following characteristics: