We here report on a 60-year-old woman of Turkish origin who was diagnosed with FMF in 2003 due to recurrent fever episodes and detection of the homozygous MEFV M694V mutation. Initially, the patient described fever episodes every 3–4 months, often in combination with abdominal or diffuse pain that improved after colchicine treatment in 2003 (dosage between 1–4 × 0.5 mg/d). Subsequently, fever episodes were less frequent but several comorbidities including atrial fibrillation, depression, knee arthroplasty, and two curatively treated malignancies (thyroid cancer 2005 and breast cancer 2012, therapies not including cerebral radiotherapy) occurred. No direct relationship between the mentioned diseases and FMF was suspected, amyloidosis as a direct comorbidity of FMF  was ruled out by rectal biopsy in 2019.
In 2020, the patient was admitted to our neurologic clinic for diagnostic work-up of unspecific neurological symptoms and abnormal MRI findings. The patient reported a slightly impaired memory, poor concentration, and absentmindedness during everyday activities in combination with headaches and more frequent fever episodes every 2–4 weeks during the last 14 months. Clinical examination was without pathologic findings except cognitive impairment (Montreal Cognitive Assessment test 16/30 points).
Due to recurrent episodes with headaches, external cerebral MRI scans had been performed in 2002 and 2008 and shown unspecific white matter lesions. Until 2019, no other neurological symptoms or relapses were reported, and the patient received no other immunomodulatory treatments than colchicine. After the occurrence of new cognitive symptoms, a follow-up MRI scan in October 2019 showed a new, ill-defined white matter lesion in the right frontal lobe, with mild local mass effect but without contrast enhancement. In the cerebral MRI from December 2020, the lesion was essentially constant in size and appearance (Fig. 1a). The additional MR spectroscopy showed markedly increased choline levels accompanied by a lactate peak, highly suggestive for a low-florid demyelinating process (Fig. 1b). Due to the lesion size > 2 cm, the slight mass effect, and the demyelinating character, we classified the right-sided frontal lobe lesion as a tumefactive demyelinating lesion . Further diagnostic procedures including brain biopsy or FET-PET were discussed with the patient but not pursued, also following the patient’s choice.
Cerebrospinal fluid (CSF) examination including cell count; protein, glucose, and IgG index; MRZ reaction; and oligoclonal IgG bands (OCB) did not show any pathological findings. There was no evidence of infectious disease (JCV PCR, HIV, hepatitis, syphilis, and Lyme serology all negative). Further laboratory investigations, including anti-aquaporin‑4, anti-MOG, and thyroid autoantibodies showed normal results. Electrophysiologic diagnostics showed delayed visual evoked potentials on the right side and delayed sensitive evoked potentials on the upper extremities (not tolerated at the lower limbs); motor evoked potentials were within normal limits.