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

2. 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

3. 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

4. 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

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

6. 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

7. 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

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

9. Questions?