Rheumatoid arthritis (RA) is a systemic inflammatory disease treated with conventional and biologic disease-modifying drugs. Methotrexate is the anchor drug for the treatment of RA and is also frequently used for various autoimmune diseases. Adverse events are common and generally easy to manage, involving mainly the gastrointestinal tract and the liver function. However, neurotoxicity is very uncommon in adults with rheumatic diseases. B cell depletion with rituximab is another therapy approach particularly in patients with refractory RA. Whistle leukoencephalopathy -namely progressive multifocal leukoencephalopathy-is an infrequent but well-described side effect of rituximab. In contrast, central nervous system toxicity due to methotrexate is extremely rare especially in RA individuals under oral or subcutaneous low dose on weekly basis. We present a challenging case of a RA patient on treatment with methotrexate and rituximab presenting with leukoencephalopathy. The patient was diagnosed with methotrexate-induced leukoencephalopathy which reversed after treatment discontinuation. We comment on the symptoms and diagnostic workout and we review the available literature on this issue based on recommendations for narrative reviews.

Besides respiratory and gastrointestinal symptoms, SARS-CoV-2 also has potential neurotropic effects. Acute hemorrhagic necrotizing encephalopathy is a rare complication of Covid-19. This article presents a case of an 81-year-old female, fully vaccinated, who underwent laparoscopic transhiatal esophagectomy due to gastroesophageal junction cancer. In the early postoperative period, the patient developed persistent fever accompanied by acute quadriplegia, impaired consciousness, and no signs of respiratory distress. Imaging with Computed Tomography and Magnetic Resonance revealed multiple bilateral lesions both in gray and white matter, as well as pulmonary embolism. Covid-19 infection was added to the differential diagnosis three weeks later, after other possible causes were excluded. The molecular test obtained at that time for coronavirus was negative. However, the high clinical suspicion index led to Covid-19 antibody testing (IgG and IgΑ), which confirmed the diagnosis. The patient was treated with corticosteroids with noticeable clinical improvement. She was discharged to a rehabilitation center. Six months later, the patient was in good general condition, although a neurological deficit was still present. This case indicates the significance of a high clinical suspicion index, based on a combination of clinical manifestations and neuroimaging, and the confirmation of the diagnosis with molecular and antibody testing. Constant awareness of a possible Covid-19 infection among hospitalized patients is mandatory.