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@ARTICLE{Brauchle:258940,
      author       = {Brauchle, Felix and Rapp, Daniel and Senel, Makbule and
                      Huss, André and Dreyhaupt, Jens and Klose, Veronika and
                      Süße, Marie and Stürner, Klarissa Hanja and Leypoldt,
                      Frank and Tumani, Hayrettin and Lewerenz, Jan},
      title        = {{C}linical associations and characteristics of the
                      polyspecific intrathecal immune response in elderly patients
                      with non-multiple sclerosis chronic autoimmune-inflammatory
                      neurological diseases - a retrospective cross-sectional
                      study.},
      journal      = {Frontiers in neurology},
      volume       = {14},
      issn         = {1664-2295},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {DZNE-2023-00706},
      pages        = {1193015},
      year         = {2023},
      abstract     = {The polyspecific intrathecal immune response (PSIIR), aka
                      MRZ reaction (M = measles, R = rubella, Z = zoster,
                      optionally Herpes simplex virus, HSV) is defined as
                      intrathecal immunoglobulin synthesis (IIS) for two or more
                      unrelated viruses. Although an established cerebrospinal
                      fluid (CSF) biomarker for multiple sclerosis (MS), a chronic
                      autoimmune-inflammatory neurological disease (CAIND) of the
                      central nervous system (CNS) usually starting in young
                      adulthood, the full spectrum of CAINDs with a positive PSIIR
                      remains ill defined.In this retrospective, cross-sectional
                      study, patients with CSF-positive oligoclonal bands (OCB)
                      and - to enrich for non-MS diagnoses - aged ≥50 years were
                      enrolled.Of 415 with PSIIR testing results (MRZ, HSV
                      optional), 76 were PSIIR-positive. Of these, 25 $(33\%)$ did
                      not meet the diagnostic criteria for MS spectrum diseases
                      (MS-S) comprising clinically or radiologically isolated
                      syndrome (CIS/RIS) or MS. PSIIR-positive non-MS-S phenotypes
                      were heterogenous with CNS, peripheral nerve and motor
                      neuron involvement and often defied unequivocal diagnostic
                      classification. A rating by neuroimmunology experts
                      suggested non-MS CAINDs in 16/25 $(64\%).$ Long-term
                      follow-up available in 13 always showed a chronically
                      progressive course. Four of five responded to immunotherapy.
                      Compared to MS-S patients, non-MS CAIND patients showed less
                      frequent CNS regions with demyelination $(25\%$ vs. $75\%)$
                      and quantitative IgG IIS $(31\%$ vs. $81\%).$ MRZ-specific
                      IIS did not differ between both groups, while additional
                      HSV-specific IIS was characteristic for non-MS CAIND
                      patients.In conclusion, PSIIR positivity occurs frequently
                      in non-MS-S patients ≥50 years. Although sometimes
                      apparently coincidental, the PSIIR seems to represent a
                      suitable biomarker for previously unnoticed chronic
                      neurologic autoimmunities, which require further
                      characterization.},
      keywords     = {MRZ reaction (Other) / autoimmue disease (Other) / multiple
                      sclerosis (Other) / neuroinflammation (Other) / polyspecific
                      intrathecal immune response (Other)},
      cin          = {AG Zhan},
      ddc          = {610},
      cid          = {I:(DE-2719)1910005},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37396770},
      pmc          = {pmc:PMC10311206},
      doi          = {10.3389/fneur.2023.1193015},
      url          = {https://pub.dzne.de/record/258940},
}