What causes neurosarcoidosis?

Updated: Nov 13, 2018
  • Author: Gabriel Bucurescu, MD, MS; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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The causes of sarcoidosis are not clear. The present evidence suggests that active sarcoidosis results from an exaggerated cellular immune response to either foreign or self-antigens. T-helper lymphocytes proliferate, resulting in an exaggerated response.

The T-helper cells undergo differentiation to a Th1-type cell under the influence of interleukin (IL)–4 and co-stimulator CD28. The Th1 cell induces IL-2 and interferon-gamma (IFN-gamma) on the macrophages, followed by a cascade of chemotactic factors that promote formation of granulomas.

IFN-gamma increases the expression of major histocompatibility class (MHC) class II receptors on macrophages, and activated macrophages carry an Fc receptor of immunoglobulin G (IgG) that potentiates their phagocytosis function. Tissue destruction results and granuloma formation is thought to be a secondary process.

Three hypotheses have been proposed to explain the mechanism, as follows:

  • A persistent antigen (either foreign or self) triggers the T-helper cell response

  • Response of the suppressor arm of the immune response is inadequate and cannot prevent T-helper cells from shutting down

  • A possible inherited or acquired (genetic) difference in response genes leads to the exaggerated response

In addition to the exaggerated cellular immune response, patients with active sarcoid demonstrate hyperglobulinemia, with antibodies against several infectious agents (eg, Mycobacterium tuberculosis) as well as IgM anti–T-cell antibodies. However, no evidence exists to suggest that these antibodies play a role in disease pathogenesis; rather, their presence seems to be due to a nonspecific polyclonal stimulation of B cells by activated T cells at the site.

A rare case of anti-Ma2 (Ma2-Ab) antibodies circulating in CSF was described in a female patient with diencephalitis thought to be paraneoplastic in origin. [3] Ma2-Abs have been described in men with testicular cancer and paraneoplastic damage to the limbic system and the diencephalon. In women, Ma2-Abs have been found in cases of lung or breast cancer.

One pediatric case of neurosarcoidosis diagnosed by brain biopsy following a La Crosse virus encephalitis has been reported. [4] The exact association was not clear, but the patient did show La Crosse virus immunoglobulins M and G in serum and cerebrospinal fluid.

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