To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest
nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated
according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System
Sarcoidosis recently proposed by Stern et al. Pathologic confrmation of granulomatous disease was
used to subclassify NS into defnite (confrmation in neurological tissue), probable (confrmation in
extraneurological tissue) and possible (no histopathological confrmation of the disease). Of the 1532
patients included in the cohort, 85 (5.5%) fulflled the Stern criteria for NS (49 women, mean age at
diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions
involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the
peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In
59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the
disease. According to the classifcation proposed by Stern et al., 11 (13%) were classifed as a defnite
NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with
the systemic phenotype of patients without NS, patients with CNS involvement presented a lower
frequency of thoracic involvement (82% vs 93%, q= 0.018), a higher frequency of ocular (27% vs 10%,
q< 0.001) and salivary gland (15% vs 4%, q= 0.002) WASOG involvements. In contrast, patients with
PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p= 0.02) in comparison with patients without NS. Neurosarcoidosis was identifed in 5.5% of patients. CNS involvement
prevails signifcantly over PNS involvement, and both conditions do not overlap in any patient. The
systemic phenotype associated to each involvement was clearly diferentiated, and can be helpful
not only in the early identifcation of neurological involvement, but also in the systemic evaluation of
patients diagnosed with neurosarcoidosis
