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paraneoplastic limbic encephalitis
Etiology:
1) mediators:
a) intracellular autoantigens:
- anti-Hu, CV2/CRMP5
b) cell-surface autoantigens
- CASPR2 (LG1), formerly thought to be VGKC
- NMDA receptor
- LBI1 protein
2) associated neoplasms:
a) small cell lung cancer
b) thymoma
c) ovarian teratoma, testicular teratoma
d) breast cancer [3]
e) Hodgkin's lymphoma
Epidemiology: rare
Pathology:
1) neuronal loss in medial temporal lobe & elsewhere in the limbic system
2) perivascular & meningeal lymphocytic infiltration
Clinical manifestations:
1) evolution over weeks to months*
- patients frequently present with neurologic symptoms prior to diagnosis of malignancy
- acute or subacute mood & behavioral changes
2) agitation
3) confusional state
4) memory loss with progession to dementia
5) seizures [2]
6) personality change
7) psychosis
8) oral dyskinesias
9) SIADH (lung cancer, thymoma)
* distinguishing from Herpes simplex encephalitis
Laboratory:
- anti-NMDA receptor antibody
- anti-AMPA receptor antibody
- anti-CASPR2
- contactin-associated protein 2 IgG in CSF
- contactin-associated protein 2 IgG in serum/plasma
- anti-Hu
- anti-CRMP5
- anti-GABA B receptor
- GABBR Ab in serum
- GABBR IgG in serum
- GABBR IgG in CSF
- voltage-gated potassium channel Ab in CSF [3]
- LG1 Ab in CSF [3]
- LGI1 Ab in CSF [3]
- CSF analysis may show lymphocytic pleocytosis
Special laboratory:
- EEG may be abnormal
Radiology:
- MRI may be abnormal
Differential diagnosis:
- Herpes simplex encephalitis evolves over days [3]
- anti-NMDA receptor encephalitis
- anti-leucine-rich glioma inactivated 1 encephalitis
Management:
1) treat empirically with intravenous acyclovir for Herpes simplex encephalitis until diagnosis is clarified [3]
2) intracellular autoantigen (+)
- generally refractory to therapy
3) cell-surface autoantigen (+)
a) removal of tumor
b) glucocorticoids
c) IV gamma-globulin
d) plasmapheresis
4) evaluation/surveillance for systemic neoplasm may need to continue for years after initial presentation
Interactions
disease interactions
Related
anti-Hu antibody (type-1 ANNA)
hippocampal 38K autoantigen
Specific
anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis
anti-NMDA receptor encephalitis; NMDAR Ab encephalitis
General
limbic encephalitis
paraneoplastic neurologic syndrome
References
- Harrison's Principles of Internal Medicine, 14th ed.
Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 624
- Tuzun E & Dalmau J
Limbic encephalitis and variants: Classification, diagnosis
and treatment.
Neurologist 2007, 13:261
PMID: 17848866
- Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19
American College of Physicians, Philadelphia 2012, 2015, 2021