Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy to Treat Essential Tremor in Nonagenarians.

Essential tremor (ET) is a disabling movement disorder that is most prevalent among the elderly. While deep brain stimulation surgery targeting the ventral intermediate nucleus of the thalamus is commonly used to treat ET, the most elderly patients or those with multiple medical comorbidities may not qualify as surgical candidates. Magnetic resonance-guided focused ultrasound (MRgFUS) constitutes a less invasive modality that may be used to perform thalamotomy without the need for a burr hole craniotomy. Here, we report on 2 patients over the age of 90 years who benefited significantly from MRgFUS thalamotomy to relieve their symptoms and improve their quality of life. The procedure was well tolerated and performed safely in both patients. We conclude that age should not be a limiting factor in the treatment of patients with MRgFUS.