Autoimmune Encephalitis Morning Report 2/22/18 Jessica Magid-Bernstein, MD, PhD

Definition Immune mediated encephalitis includes paraneoplastic and autoimmune types Paraneoplastic encephalitidies Always cancer related Autoimmune encephalitidies Associated with antibodies against neuronal cell surface and synaptic proteins May or may not be cancer-associated

Clinical Presentation Wide clinical spectrum Typical limbic encephalitis – evolves over days to weeks Acute or subacute mood and behavior changes Short term memory problems Focal seizures with impaired awareness Cognitive dysfunction Hypothalamic dysfunction may occur – hyperthermia, somnolence, endocrine abnormalities Complex neuropsychiatric symptoms Deficits of memory, cognition, psychosis, seizures, abnormal movements, or coma

Diagnosis Broad differential to rule out Workup EEG LP Imaging with MRI Exclude alternative diagnoses FLAIR hyperintensities, +/- enhancement EEG NMDA – delta brush Exclude non-convulsive seizures Some types associated with seizures LP May be normal Exclude alternative diagnoses May see: elevated protein, lymphocytic pleocytosis, elevated IgG index, OCBs Differential includes -  The differential diagnosis of autoimmune or paraneoplastic encephalitis includes a variety of alternative causes of encephalitis and encephalopathy. Broad categories include infection, toxic and metabolic disturbances, vascular disorders, neoplastic disorders, demyelinating and inflammatory disorders, psychiatric disease, neurodegenerative dementias, and rare heritable or metabolic disorders (table 4).   Some clinical syndromes, such as limbic encephalitis, may initially have a wide differential diagnosis. For example, metastatic disease affecting the brain or leptomeninges, viral encephalitis, Creutzfeldt-Jakob disease, ischemic and hemorrhagic cerebrovascular disease, Whipple disease, psychiatric disease, toxic-metabolic encephalopathy, Wernicke encephalopathy, and primary degenerative dementia have all been reported to cause a clinical syndrome for which the diagnosis of paraneoplastic or autoimmune limbic encephalitis was considered radiopaedia.org

Diagnosis – antibody testing Test serum and CSF Be weary of serum Abs only, more likely to be false positive Correlate with clinical syndrome

Specific syndromes Anti-NMDA – prominent psychiatric manifestations; most associated with ovarian teratoma Anti-LGI1 (previously attributed to VGKC Abs) – memory problems, confusion, FBD seizures; CSF often normal Anti-CASPR2 (previously attributed to VGKC Abs) – older men, slower course, usually a/w thymoma Anti-AMPA – usually women, limbic encephalitis +/- seizures, 2/3 a/w neoplasm (lung, thymus, breast) Anti-GABA-A – rapid and progressive, a/w status epilepticus and/or EPC, 50% in children Anti-GABA-B – adults; often includes seizures, ataxia, or opsoclonus-myoclonus; 50% a/w SCLC Anti-IgLON5 – REM and non-REM parasomnias, OSA, very poor prognosis, pTau on autopsy DPPX-associated – central hyperexcitability; CSF lymph pleocytosis; often relapse Dipeptidyl-peptidase–like protein-6 IgLON5 – neuronal cell adhesion protein

Treatment Treat as soon as infection is ruled out Damage occurs rapidly and is often irreversible Immunotherapy is gold standard IVIg Glucocorticoids PLEX Cyclophosphamide Rituximab Antibody titers often do not correlate with disease Treat seizures aggressively – often do not require long-term AEDs Variable prognosis – depends on timing of diagnosis/treatment, also specific syndrome

References Dalmau, J. & Rosenfeld, M. (2018). Paraneoplastic and autoimmune encephalitis. In A. F. Eichler (Ed.), UpToDate. Retrieved February 21, 2018, from https://www.uptodate.com/contents/paraneoplastic-and-autoimmune-encephalitis Van Sonderen, A, et al. (2016). Anti-LGI1 encephalitis: Clinical syndrome and long-term follow up. Neurology. 87:1449-1456. Van Sonderen, A, et al. (2016). From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over time. Autoimmunity Reviews. 15:970-974.

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