Conceptualizing Autoimmune & Paraneoplastic Limbic Encephalitis

Paraneoplastic and Autoimmune Encephalitis refers to a heterogeneous group of neurologic conditions whereby autoantibody formation disrupts normal neuronal and neurologic function. Because of their relatively recent discovery (basically last 20 years), more and more cases are being recognized in the clinical setting, and more and more patients are being suspected of having “autoimmune encephalitis.” However, I would caution any provider against considering autoimmune or paraneoplastic encephalitis in the differential diagnosis of a patient with unexplained altered mental status. As protean as some of these conditions may be, each is phenotypically distinct and should be appreciated as such. Take for instance the autoantibody-mediated condition myasthenia gravis, as we have previously showcased on BrainWaves.

In addition to organizing these conditions according to the phenotype (e.g., faciobrachial dystonic seizures in anti-LGI-1 encephalitis, or psychosis with hypoventilation in anti-NMDA encephalitis), neurologists may organize these disorders according to the neural substrate that is affected–e.g., paraneoplastic degeneration (Yo, Tr), limbic encephalitis (LGI-1, NMDA, Hu), stiff-person syndrome (GAD, ampyphysin), opsoclonus-myoclonus-ataxia (neuroblastoma-associated), etc. Among the limbic encephalitides, which is the focus of this week’s episode, you could even further distinguish cell-surface antibody (NMDA, LGI-1) from the intracellular antibody-associated encephalitides (CRMP, Hu, Ma2). These are predominantly helpful in guiding treatment and aiding the provider in prognostication, where intracellular-antibody associated encephalitis has a generally poorer prognosis when compared to the cell-surface antibody associated encephalitides.

LGI1

Axial FLAIR sequence of an 82-year-old male with a history of melanoma (s/p resection) who presented with rapidly progressive dementia and myoclonic jerks, found to have anti-LGI-1 encephalitis.

But this is all academic. When should you consider testing for paraneoplastic or autoimmune encephalitis? The differential diagnosis for each subgroup of encephalitides can be incredibly broad and should be thoroughly evaluated when these conditions are considered: for example, HSV and syphilis should be assessed in patients with suspected limbic encephalitis. Imaging can assist in some cases, and particularly with limbic encephalitis you may see mesial temporal lobe T2 prolongation (figure) in 70-80% of patients. Electroencephalography may also be helpful, for example, extreme delta brush has been reported in one-third of cases of NMDA receptor encephalitis. The CSF profile may raise some flags, but is non-specific. A mild pleocytosis or slight elevation in protein is not uncommon for autoimmune encephalitides. But diagnosis relies on antibody detection in the cerebrospinal fluid, and while this may be expensive, deferral of this testing may prove even more costly to the patient if the disease progresses without appropriate and early intervention.

 

[Jim Siegler]


The content in this episode was vetted and approved by Ramani Balu.

REFERENCES

Anderson NE and Barber PA. Limbic encephalitis – a review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2008;15:961-71.

Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J and Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012;79:1094-100.

Lancaster E, Martinez-Hernandez E and Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011;77:179-89.

Rosenfeld MR and Dalmau JO. Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis. Continuum (Minneap Minn). 2012;18:366-83.

Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F and Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology. 2013;12:157-65.

Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, Schott JM, Armstrong RJ, A SZ, Bleasel A, Somerville ER, Smith SM and Vincent A. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Annals of neurology. 2011;69:892-900.

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