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  • Updated 06.17.2022
  • Released 06.17.2022
  • Expires For CME 06.17.2025

Perspectives: Dr. Josep Dalmau and autoimmune encephalitis

Interview questions

• [01:14] Can you tell us about your early life? How did you get interested in neurology?

• [03:17] How did you get the appointment at Memorial Sloan Kettering Cancer Center? Who or what influenced you?

• [07:08] How did you get interested in paraneoplastic encephalitis?

• [09:46] Tell us more about your academic affiliations since your appointment at Memorial Sloan Kettering.

• [14:50] Tell us about your current appointments

• [18:17] It has now been 10 years since the initial descriptions of anti-NMDAR encephalitis. In what direction should we continue this research?

• [22:18] Do you think these diseases were always present?

• [25:06] Are you interested in the MS field, and do you see any parallels between the MS field and these neuro-oncology syndromes?

• [30:48] What are your goals for the future? What do you see yourself doing over the next 5 to 10 years?

• [35:10] What kind of advice do you give medical students and residents?

Short biography

While studying the remote effects of cancer on the brain, Dr. Dalmau discovered a category of diseases named antibody-mediated encephalitis, starting with anti-NMDA receptor encephalitis, reported with his associates in 2007, while he was at the University of Pennsylvania. These diseases occur in association with antibodies against neuronal cell-surface proteins, ion channels, or synaptic receptors involved in synaptic transmission and plasticity and have implications for the cellular and molecular mechanisms underlying the immune-mediated brain dysfunction. Antibody-mediated changes in the structure or function of these antigens result in several different syndromes characterized by psychosis, behavioral changes, seizures, memory deficits, abnormal movements, sleep dysfunction, or cognitive decline. In some patients, benign tumors and cancers, including those of the lung, breast, ovaries, and blood, are associated with these diseases.

Dr. Dalmau is now recognized as a world authority on autoimmune and paraneoplastic disorders affecting the nervous system. Dr. Dalmau was born and raised in Barcelona, Spain, and received his MD and PhD degrees from the Autonoma University of Barcelona, where he completed a residency in neurology. He trained in neuro-oncology, a specialty that deals with tumors of the nervous system, at Memorial Sloan-Kettering Cancer Center in New York, where he was later appointed to the faculty. After 11 years at Sloan-Kettering, Dr. Dalmau became co-director of neuro-oncology at the University of Arkansas for Medical Sciences. In 2002, he moved to the Department of Neurology and Abramson Cancer Center of the University of Pennsylvania. Currently Dalmau combines his activity at the University of Pennsylvania with a position as ICREA Research Professor at IDIBAPS, Hospital Clinic of the University of Barcelona.

In 2015, Dr. Dalmau was elected to the National Academy of Medicine, one of the highest honors in the fields of health and medicine. He has published over 320 manuscripts in leading journals, and his papers are among the most cited in his field. In 2015, Dr. Dalmau was listed by Thomson Reuters as one of the most highly cited investigators in the world in the fields of behavior and neuroscience. He has received numerous awards, including among others the Career Award (European Society of Neuroimmunology), Developmental Clinical Oncology Career Award (American Cancer Society), Frontiers in Clinical Neuroscience Award (American Academy of Neurology), George W. Jacoby Award (American Neurological Association), Editors of Brain Award (Association of British Neurologists), Neuroscience of Brain Disorders Award (McKnight Foundation), the Zülch Prize for Basic Neurological Research (Max Planck Society, Cologne, Germany), the Sobek Foundation award (Stuttgart, Germany), the Foundation Rey Jaime I Award (Valencia, Spain), and Neuroscience Research Program Award (Charles A. Dana Foundation).

Dr. Dalmau’s research has been funded by the National Institutes of Health, the Spanish Health Institute, the Charles A Dana Foundation, the McKnight Foundation, and the American Cancer Society, among others.

Autoimmune encephalitis disorders

Dr. Dalmau and associates have identified antibody-mediated autoimmune encephalitis disorders related to the following receptors.

NMDA receptor

AMPA receptor

GABAb receptor

GABAa receptor

DPPX

mGluR5

mGluR2

Neurexin

GluK2 (Kainate receptor)

Sez6l2

LGI1 (discovered simultaneous by my group and another group of investigators)

IgLON5 (in collaboration with Francesc Graus and Lidia Sabater)

Ma2

Autoimmune encephalitis post-herpes simplex encephalitis (associated with NMDAR or multiple antibodies).

References

01
Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005;128(Pt 8):1764-77. PMID 15888538
02
Armangue T, Spatola M, Vlagea A, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 2018;17(9):760-772. PMID 30049614
03
Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7(12):1091-8. PMID 18851928
04
Dalmau J, Graus F. Autoimmune Encephalitis and Related Disorders of the Nervous System. Cambridge Univ Press, 2022.
05
Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61(1):25-36. PMID 17262855
06
Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15(4):391-404. PMID 26906964
07
Hughes EG, Peng X, Gleichman AJ, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010;30(17):5866-75. PMID 20427647
08
Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009;65(4):424-34. PMID 19338055
09
Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010;9(8):776-85. PMID 20580615
10
Lancaster E, Huijbers MG, Bar V, et al. Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol 2011;69(2):303-11. PMID 21387375
11
Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol 2010;9(1):67-76. PMID 19962348
12
Lancaster E, Martinez-Hernandez E, et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011;77(18):1698-701. PMID 22013185
13
Petit-Pedrol M, Armangue T, Peng X, et al. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 2014;13(3):276-86 PMID 24462240
14
Petit-Pedrol M, Sell J, Planagumà J, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain 20181;141(11):3144-3159. PMID 30346486
15
Planagumà J, Leypoldt F, Mannara F, et al. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain. 2015 Jan;138(Pt 1):94-109. PMID 25392198
16
Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157-65. PMID 23290630

Contributors

Author

  • Dalmau J

    Josep Dalmau MD PhD

    Dr. Dalmau of IDIBAPS, University of Barcelona, receives royalties from Euroimmun for intellectual property rights and contracted research funds from Euroimmun as a principal investigator, has served as a consultant to Astellas Research Institute of America and Janssen Research & Development, and has received research funding from Sage Therapeutics

    See Profile

Editor

  • Aprr

    Raymond P Roos MD

    Dr. Roos serves on the Scientific Advisory Board of Revalesio Corporation and received consulting fees from Best Doctors and Guidepoint Network. He also owns stock in Amgen, Express Script, Ionis, Merck, Pfizer, and Cigna.

    See Profile

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