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Autoimmune Encephalitis: Paraneoplastic Syndromes

  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 391 Downloads

Abstract

Paraneoplastic disorders are caused by cancer but not by a direct result of cancer invasion of the affected tissue or organ. Neurologic signs and symptoms result from either direct or indirect damage to the nervous system. Autoimmune encephalitis (AE) is a diverse group of neuropsychiatric disorders associated with systemic autoimmune disorders, CNS autoimmune disorders, and paraneoplastic syndromes. AE is mediated by antibodies (Abs) directed against membrane receptors (e.g., N-methyl d-aspartate receptors) and ion channel-associated CNS proteins (e.g., voltage-gated potassium channels).

During the last two decades, a variety of disorders have been clinically recognized and the causing autoantibody identified. Autoimmune encephalitides include limbic encephalitis (LE), paraneoplastic limbic encephalitis (PLE), NMDA-R encephalitis, voltage-gated potassium antibody syndromes (LGI1, contactin-associated protein like (CASPR2)), Morvan syndrome, AMPAR (GluR1, GluR2) antibody syndrome, glycine receptor antibody syndrome, dopamine 2 receptor antibody syndrome (D2RA), GABA receptor Ab syndrome, metabotropic glutamate receptor antibody syndrome, and IgLON5 Ab syndrome.

Radiologically, these disorders show initial edema, later atrophy of affected region (limbic encephalitis, rhombencephalitis). Imaging without pathological findings does not exclude paraneoplastic syndromes.

Histologically, variable loss of neurons in the hippocampal formation is seen. Gliomesenchymal nodules, neuronal damage, softening of the tissue, and perivascular lymphocytic infiltrates are seen.

Paraneoplastic encephalitis results from immune responses against intraneuronal proteins, ectopic expression of neuronal proteins triggers immune response misdirected against the nervous system, antigens released by apoptotic tumor cells are taken up and processed by antigen-presenting cells at the regional lymph node, presented to the immune system eliciting an anti-tumor immune response, prominent cytotoxic T-cell responses, and neuronal degeneration via perforin or granzyme-related mechanisms.

In autoimmune encephalitis, antibodies access cell surface targets and alter their structure and function by cross-linking and internalization of the receptors leading to a functional blocking of receptors. Priming B-cell immune responses lead to production of autoantibodies with functional and reversible rather than structural and irreversible neuronal alteration. Predisposition to autoimmunity results from genetic susceptibility (HLA associations with LGI1 and IgLON5 antibodies).

Treatment consists in finding and treating the cancer. Immunity suppression of predominantly T-cell suppression with corticosteroids, cyclophosphamide, tacrolimus, stem cell transplantation and of predominantly B-cell suppression with plasma exchange, intravenous immunoglobulin (IVIG), or antibodies (e.g., rituximab). Control of symptoms (ataxia, stiff muscle, weakness, pain, cognitive dysfunction, and seizures). Outcome is variable depending on the underlying mechanisms, i.e., intracellular-onconeural (10–30% of patients with mild response, infrequent relapses, usually monophasic and irreversible), intracellular-synaptic (about 60% of patients have partial improvement, infrequent relapses, symptoms may fluctuate), and cell surface or synaptic receptor (substantial or full recoveries).

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

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