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Background: Infectious mononucleosis (IM) is an acute disease caused by Epstein-Barr virus (EBV) infection which affects adolescents and young adults. Clinically, IM is manifested by fever, lymphadenopathy and tonsillar pharyngitis. Neurological complications of IM include cranial nerve palsy, encephalitis, aseptic meningitis, transverse myelitis, peripheral neuritis, optic neuritis, encephalomyelitis, and rarely Guillain-Barré syndrome (GBS), especially the so-called overlapping/atypical variants, which in some cases can be life-threatening. Aim: The aim was to present a very rare and educational example of neurological complications during isolated reactivation of EBV infection in 15-year-old previously healthy girl. During hospitalization, she developed very serious neurological complications, as well as mesial temporal sclerosis and a minor cognitive deficit upon recovery. Case report: A 15-year-old girl was admitted for hospital treatment on the third day of a febrile illness with symptoms of viral meningoencephalitis. On the sixth day of hospitalization, she developed a series of generalized onset motor tonic-clonic seizures. A brain MRI showed diffuse meningitis and encephalitis localized in the left temporal region. EBV was proven from the cerebrospinal fluid. Other possible infectious causes were excluded. From the 14th day of hospitalization, the treatment was complicated by the development of Gullian-Barre syndrome and Miller-Fischer syndrome. Immunological processing was normal. Anti-MOG, antiganglioside antibodies, aquaporin antibodies, and panel for autoimmune encephalitis were negative. The therapy consisted of antiviral and anti-inflammatory medications and 8 cycles of plasmapheresis and levetiracetam as an anticonvulsant drug. With physical therapy there is no motor deficit, but she has learning difficulties, and mesial temporal sclerosis on the control brain MRI. Conclusion: With this clinical presentation it was necessary to exclude optic neuritis, multiple sclerosis, acute disseminated encephalomyelitis and myelin oligodendrocyte glycoprotein antibody-associated disease. Clinical monitoring, prevention of epileptic seizures with properly chosen antiepileptic therapy, and well-chosen timing of neurosurgical intervention will be especially demanding. [ABSTRACT FROM AUTHOR]