Abstract Background Lyme disease (LD), caused by Borrelia burgdorferi sensu lato’s species, has a wide presentation and severity and is often a neglected diagnosis. Neuroborreliosis (NB) occurs in 10-15% of patients (pts). This study evaluate NB (clinical manifestations, treatment and evolution) in a district acute hospital in Portugal. Methods Pts with Borrelia burgdorferi antibodies detected by ELISA, confirmed by Immunoblot and with neurological manifestations, between January 2015 - April 2022, in Pedro Hispano Hospital, Matosinhos, Portugal. Results Twenty-one pts: encephalitis (n=5), optic neuropathy (n=5), peripheral neuropathy (n=5), VII cranial nerve palsy (n=4), meningitis (n=3), myelitis (n=2), III cranial nerve palsy (n=1), meningoradiculitis (n=1), radiculitis (n=1) and stroke (n=1); majority female (71.4%) with mean age 50.8 years old. No cases of erythema migrans or arthralgias were observed. ECG performed in 13 pts and only one intraventricular conduction block detected. Lumbar puncture performed in 15 pts, only two presented inflammatory cerebrospinal fluid. Therapeutic strategies: 28 (n=4), 21 (n=5), 14 (n=3) and 10 (n=1) days of ceftriaxone and 28 (n=4), 21 (n=2) and 14 (n=2) days of doxycycline were applied. Complete clinical resolution observed in 6 pts (28.6%) and clinical improvement in 10 (47.6%). One (4.8%) developed post-treatment Lyme disease syndrome and one death occurred, not related with LD. Three pts had no clinical improvement but there was not disease progression, two treated with doxycycline (28 days) and the other one with ceftriaxone (21 days). Conclusion These data show the non-negligible prevalence of NB and the variability of clinical presentations that requires a high suspicion in the differential diagnosis. The heterogeneity of therapeutic regimens reflects the absence of a well-defined treatment and opens this discussion. Disclosures All Authors: No reported disclosures.