CSF-based liquid biopsy pointing to a diagnosis of diffuse glioma in a patient with supposed neurodegenerative disorder.

INTRODUCTION: The differential diagnosis of brain diseases becomes challenging in cases where imaging is not sufficiently informative, and surgical biopsy is impossible or unacceptable to the patient. METHODS: An elderly patient with progressive short-term memory loss and cognitive impairment presented with a normal brain CT scan, a brain FDG-PET that indicated symmetrical deterioration of the white matter in the frontal lobes, and inconclusive results of a molecular marker analysis of suspected dementia in cerebrospinal fluid (CSF). Brain MRI suggested the diagnosis of lower grade glioma. The patient refused surgical biopsy. In order to investigate whether somatic mutations associated with gliomas existed, we performed a "liquid biopsy" by the targeted sequencing of cell-free DNA (cfDNA) from his CSF. RESULTS: Deep sequencing of the cfDNA from CSF revealed somatic mutations characteristically found in gliomas, including mutations of the TP53 (Arg282Trp), BRAF (Val600Glu), and IDH1 (Arg132His) genes. The patient is currently treated with temozolomide, and his clinical and MRI findings suggest the stabilization of his disease. CONCLUSION: Neurological patients may benefit from liquid biopsy diagnostic work-up as it can reveal therapeutically targetable mutations.

Long term follow-up in advanced Parkinson's disease treated with DBS of the subthalamic nucleus.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been an approved treatment for PD for more than 30 years, but few data are available regarding its long-term effectiveness. OBJECTIVE: The aim of this study is to evaluate patients' outcome, both from a motor and non-motor perspective, 9 to 14 years after DBS implantation. We have investigated patients with advanced PD and treated with STN-DBS, in relation to key clinical features of PD. METHODS: 18 patients were assessed both retrospectively and prospectively. They underwent motor examination, neuropsychological evaluation and questionnaires on the quality of life, preoperatively, as well as 1, 9 and 14 years after DBS surgery. All patients were implanted with STN-DBS at San Raffaele Hospital between 2004 and 2010. RESULTS: 13 males and five females underwent DBS implantation with a mean PD duration of 11 years. Stimulation significantly improved med-off/stim-on condition up to 9 years, compared to the preoperative off state, and med-on/stim-on condition at 14 years, compared to med-on/stim-off state. Long term improvement specifically involved tremor and rigidity, as well as dopaminergic daily dose. At the same time, STN-DBS had no long-lasting effect on axial symptoms and cognitive functions. CONCLUSIONS: STN-DBS remains an effective therapy for advanced PD, also over the years. Despite the underlying progression of the disease, this treatment extends the period in which the overall quality of life is still acceptable.