Brain metastases (BMs) are the most common intracranial tumours in adults and occur up to 3–10 times more frequently than primary brain tumours. BMs may be the cause of the neurological presenting symptoms in patients with otherwise previously undiagnosed cancer. In up to 15% of patients with BMs, the primary tumour cannot be identified. These cases are known as BM of cancer of unknown primary (CUP) (BM-CUP). CUP has an early and aggressive metastatic spread, poor response to chemotherapy, and poor prognosis. The pathogenesis of CUP seems to be characterized by a specific underlying pro-metastatic signature. The understanding of BM-CUP, despite its relative frequency and unfavourable outcome, is still incomplete and clear indications on management are missing. Advances in diagnostic tools, molecular characterization, and target therapy have shifted the paradigm in the approach to metastasis from CUP: while earlier studies stressed the importance of finding the primary tumour and deciding on treatment based on the primary diagnosis, most recent studies focus on the importance of identifying targetable molecular markers in the metastasis itself. The aim of this review is to summarize current evidence on BM-CUP, from the diagnosis and pathogenesis to the treatment, with a focus on available studies and ongoing clinical trials.

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by tics and, frequently, psychiatric and behavioral comorbidities. Above all, obsessive compulsive disorder/behavior (OCD/OCB) influences the clinical picture and has a severe impact on quality of life, eventually more than the tics themselves. Deep brain stimulation (DBS) is an effective therapy in selected, refractory cases. Clinical response to DBS may vary according to the clinical picture, comorbidities, and to the anatomical target. This retrospective study compares the results obtained from DBS in the ventralis oralis/centromedian-parascicular nucleus of the thalamus (Voi-Cm/Pf) (41 patients) and antero-medial Globus Pallidus internus (am-GPi) (14 patients), evaluating clinical response over time by means of Yale Global Tic Severity Scale (YGTSS) and Yale–Brown Obsessive-Compulsive Scale (YBOCS) scores over a period of 48 months. A significant and stable improvement in the YGTSS and YBOCS has been obtained in both groups (p < 0.001). There was a significant difference in YBOCS improvement over time between the am-GPi group and the Voi-Cm/Pf group, indicating a better and faster control of OCD/OCB symptoms in the former group. The ratio of hardware removal was 23% and limited to 13 patients in the Voi-Cm/Pf group. These results confirm that DBS is an effective therapy in treating GTS and suggest that the am-GPi might be superior to Voi-Cm/Pf in alleviating comorbid OCD/OCB.

The structural and functional organization of the brain connectome constructed using MRI showed the potential to predict atrophy progression in patients with early-stage, mild Parkinson disease.