Premium
Cerebrospinal fluid cyto‐/chemokine profile during acute herpes simplex virus induced anti‐ N ‐methyl‐ d ‐aspartate receptor encephalitis and in chronic neurological sequelae
Author(s) -
Kothur Kavitha,
Gill Deepak,
Wong Melanie,
Mohammad Shekeeb S,
Bandodkar Sushil,
Arbunckle Susan,
Wienholt Louise,
Dale Russell C
Publication year - 2017
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.13431
Subject(s) - encephalitis , cxcl13 , cxcl9 , immunology , chemokine , medicine , herpes simplex virus , cerebrospinal fluid , cxcl10 , chemokine receptor , inflammation , virus , pathology
Aim To examine the cytokine/chemokine profile of cerebrospinal fluid ( CSF ) during acute herpes simplex virus‐induced N ‐methyl‐ d ‐aspartate receptor ( NMDAR ) autoimmunity and in chronic/relapsing post‐herpes simplex virus encephalitis ( HSE ) neurological syndromes. Method We measured longitudinal serial CSF cyto‐/chemokines ( n =34) and a glial marker (calcium‐binding astroglial protein, S100B) in one patient during acute HSE and subsequent anti‐ NMDAR encephalitis, and compared the results with those from two patients with anti‐ NMDAR encephalitis without preceding HSE. We also compared cyto‐/chemokines in cross‐sectional CSF samples from three children with previous HSE who had ongoing chronic or relapsing neurological symptoms (2yr 9 mo–16y after HSE ) with those in a group of children having non‐inflammatory neurological conditions ( n =20). Results Acute HSE showed elevation of a broad range of all T‐helper‐subset‐related cyto‐/chemokines and S100B whereas the post‐ HSE anti‐ NMDAR encephalitis phase showed persistent elevation of two of five T‐helper‐1 (chemokine [C‐X‐C motif] ligand 9 [ CXCL 9], CXCL 10), three of five predominantly B‐cell ( CXCL 13, CCL 19, a proliferation‐inducing ligand [ APRIL ])‐mediated cyto‐/chemokines, and interferon‐ α . The post‐ HSE anti‐ NMDAR encephalitis inflammatory response was more pronounced than anti‐ NMDAR encephalitis. All three chronic post‐ HSE cases showed persistent elevation of CXCL 9, CXCL 10, and interferon‐ α , and there was histopathological evidence of chronic lymphocytic inflammation in one biopsied case 7 years after HSE . Two of three chronic cases showed a modest response to immune therapy. Interpretation HSE ‐induced anti‐ NMDAR encephalitis is a complex and pronounced inflammatory syndrome. There is persistent CSF upregulation of cyto‐/chemokines in chronic or relapsing post‐ HSE neurological symptoms, which may be modifiable with immune therapy. The elevated cyto‐/chemokines may be targets of monoclonal therapies.