Table 2.
Features That Should Raise Suspicion of Neuronal-Surface–Directed Antibodies in Patients Presenting with Cognitive Impairment, Psychiatric Features, Epilepsy, Movement Disorders, or Demyelinating Disease
| Clinical Syndrome | |||||
|---|---|---|---|---|---|
| Cognitive Impairment | Psychiatric | Epilepsy | Movement Disorders | Demyelinating Disease | |
| Onseta | Rapid | Rapid without a Prodrome of Social Withdrawal | Rapid, Especially When No Prior Seizure History | Rapid | Acute Relapses |
| Clinical Features | Memory as a conspicuously affected cognitive domain; often associated seizures including FBDS and hyponatremia (with VGKCc/LGI1-antibodies); underlying cancer possible (GABABR/AMPAR) | First lifetime episode of psychosis; associated seizure(s) and movement disorder (NMDAR/AMPAR); neuromyotonia, dysautonomia, and insomnia (Morvan: CASPR2 > LGI1) | Frequent, localization-related seizures; associated cognitive/psychiatric features in young females (often NMDAR/GAD) or middle-age (VGKCc/LGI1) | Variable phenomenologies including chorea, dystonia, and stereotypies; associated neuropsychiatric features such as anxiety, OCD, or depression (NMDAR/D2R); ataxia (CASPR2, GAD, mGluR1/5); preceding streptococcal infection; hyperekplexia and rigidity (glycine, DPPX) | LETM, severe/bilateral ON, intractable nausea with medullary lesion, drug-refractory pain, often with poor spontaneous recovery (AQP4) or overall better prognosis (MOG) |
| MRI and CSF (protein, cells, oligoclonal bands) findings | T2/FLAIR hyperintensity on brain MRI, particularly in medial temporal lobes; normal CSF usually | Various subcortical or cortical T2/FLAIR changes; some appearances suggestive of demyelination; CSF pleocytosis and oligoclonal bands | T2/FLAIR hyperintensity on brain MRI, particularly in medial temporal lobes; normal CSF usually | Usually normal, sometimes medial temporal lobe hyperintensities; often normal CSF | White matter lesions can look very similar to MS; brain may be normal; longitudinally extensive myelitis; CSF typically shows pleocytosis without bands |
| Associated cell-surface–directed antibodies | VGKCc (LGI1, CASPR2), AMPAR, GABABR, GAD, DPPX | NMDAR; LGI1 and CASPR2; D2R; AMPAR | VGKCc (especially LGI1), GAD, NMDAR | NMDAR, glycine, VGKCc, GAD, DPPX, D2R | AQP4, MOG |
One feature common to many of these presentations is the rapid onset, often within days to a few weeks. Routine CSF examination is normal in many cases, especially VGKC-complex antibodies, with variable presence of oligoclonal bands and raised immunoglobulin G index.
AMPAR = α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; AQP4 = aquaporin-4; CASPR2 = contactin-associated protein 2; CSF = cerebrospinal fluid; D2R = dopamine receptor D2; DPPX = dipeptidyl peptidase IV–related protein; FBDS = faciobrachial dystonic seizures; FLAIR = fluid-attenuated inversion recovery; GABABR = γ-aminobutyric acidB receptor; GAD = glutamic acid decarboxylase; LETM = longitudinally extensive transverse myelitis; LGI1 = leucine-rich glioma-inactivated 1; mGluR = metabotropic glutamatergic receptor; MOG = myelin oligodendrocyte glycoprotein; MRI = magnetic resonance imaging; MS = multiple sclerosis; NMDAR = N-methyl-D-aspartate receptor; OCD = obsessive–compulsive disorder; ON = optic neuritis; VGKCc = voltage-gated potassium channel complex.