D. Fritz

Research output: PhD ThesisPhD-Thesis - Research and graduation internal


Sarcoidosis is characterized by noncaseating granulomatous inflammation with unknown cause. In 5% of sarcoidosis patients, it affects the nervous system: neurosarcoidosis. In this thesis we describe genetic predisposition, clinical characteristics, ancillary investigations, efficacy of immunosuppressive treatment, and outcome of neurosarcoidosis.
We conducted whole genome sequencing in a family with a high prevalence of sarcoidosis, with variants in the genes JAK2, BACH2 and NCF1 with previous associations with inflammatory disease. Furthermore, we found that 71% primarily presented with neurological symptoms, chronic meningitis in one-third, cranial nerve palsy in one-third, and myelopathy in one-fifth. Ancillary investigations are often not conclusive. Elevated serum ACE was found in 44%, signs of inflammation in the cerebrospinal fluid in 58% and abnormal MRI brain in 70%. The 18F-FDG PET-CT scan was suggestive for sarcoidosis in 22%, leading to a biopsy proven diagnosis in 11 of 20 patients (55%). Although new treatments are increasingly used, the mortality rate remains 5% and one-third does not have a substantial clinical improvement on treatment. Infliximab, a TNF-α antagonist, is an effective treatment and led to remission or improvement in 71%. However, we found a relatively high mortality rate, partly reflecting severity of disease in infliximab treated patients and treatment associated complications.
Neurosarcoidosis is a diverse and challenging disease with a need for an individualized treatment plan and centralization of care in centers of excellence. Prospective studies should shed light on the accuracy of the criteria and treatment effects. Randomized trials are urgently needed to evaluate efficacy and safety of Infliximab.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • van de Beek, Diederik, Supervisor
  • Brouwer, Matthijs C., Co-supervisor
  • Eftimov, Filip, Co-supervisor
Award date21 Jan 2022
Print ISBNs9789463328166
Publication statusPublished - 2022

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