Brain Advance Access published online on May 11, 2005
Brain, doi:10.1093/brain/awh526
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [18F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.
Received December 20, 2004
Revised April 1, 2005
Accepted April 3, 2005
Article
Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates
2 Department of Neurosurgery, Medical College of Georgia, Augusta, GA, USA
3 Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
Josep Dalmau, E-mail: jdalmau{at}mail.med.upenn.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Graus, A. Saiz, M. Lai, J. Bruna, F. Lopez, L. Sabater, Y. Blanco, M. J. Rey, T. Ribalta, and J. Dalmau Neuronal surface antigen antibodies in limbic encephalitis: Clinical-immunologic associations Neurology, September 16, 2008; 71(12): 930 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saiz, Y. Blanco, L. Sabater, F. Gonzalez, L. Bataller, R. Casamitjana, L. Ramio-Torrenta, and F. Graus Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association Brain, August 7, 2008; (2008) awn183v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Novillo-Lopez, J. E. Rossi, J. Dalmau, and J. Masjuan TREATMENT-RESPONSIVE SUBACUTE LIMBIC ENCEPHALITIS AND NMDA RECEPTOR ANTIBODIES IN A MAN Neurology, February 26, 2008; 70(9): 728 - 729. [Full Text] [PDF]
|
|
|
|
|
|
F. Graus and A. Saiz Limbic encephalitis: An expanding concept Neurology, February 12, 2008; 70(7): 500 - 501. [Full Text] [PDF]
|
|
|
|
|
|
T. Iizuka, F. Sakai, T. Ide, T. Monzen, S. Yoshii, M. Iigaya, K. Suzuki, D. R. Lynch, N. Suzuki, T. Hata, et al. Anti-NMDA receptor encephalitis in Japan: Long-term outcome without tumor removal Neurology, February 12, 2008; 70(7): 504 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Khella, N. Souyah, and J. Dalmau THYMOMA, MYASTHENIA GRAVIS, ENCEPHALITIS, AND A NOVEL ANTICYTOPLASMIC NEURONAL ANTIBODY Neurology, September 18, 2007; 69(12): 1302 - 1303. [Full Text] [PDF]
|
|
|
|
 |
|
 L Bataller, K A Kleopa, G F Wu, J E Rossi, M R Rosenfeld, and J Dalmau Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes J. Neurol. Neurosurg. Psychiatry, April 1, 2007; 78(4): 381 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S R Samarasekera, A Vincent, J L Welch, M Jackson, P Nichols, and T D Griffiths Course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies J. Neurol. Neurosurg. Psychiatry, April 1, 2007; 78(4): 391 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dalmau, R. G. Gonzalez, and M. F. Lerwill Case 4-2007 -- A 56-Year-Old Woman with Rapidly Progressive Vertigo and Ataxia N. Engl. J. Med., February 8, 2007; 356(6): 612 - 620. [Full Text] [PDF]
|
|
|
|
 |
|
 U. D. Parthasarathi, T. Harrower, M. Tempest, J. R. Hodges, C. Walsh, P. J. McKenna, and P. C. Fletcher Psychiatric presentation of voltage-gated potassium channel antibody-associated encephalopathy: Case report The British Journal of Psychiatry, August 1, 2006; 189(2): 182 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M Schott Limbic encephalitis: a clinician's guide Practical Neurology, June 1, 2006; 6(3): 143 - 153. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Kleopa, L. B. Elman, B. Lang, A. Vincent, and S. S. Scherer Neuromyotonia and limbic encephalitis sera target mature Shaker-type K+ channels: subunit specificity correlates with clinical manifestations Brain, June 1, 2006; 129(6): 1570 - 1584. [Abstract] [Full Text] [PDF]
|
|