ObjectiveThe efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30‐Hz low‐frequency stimulation designed to overdrive neuronal activity by dual pallido‐thalamic targeting, using the Coma Recovery Scale Revised (CRS‐R) to assess conscious behavior.MethodsWe conducted a prospective, single center, observational 11‐month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5‐month ON and OFF periods; and unblinded, 5‐month stimulation ON. Five adult patients were included: one unresponsive‐wakefulness‐syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS‐R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON – baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random‐effect models.ResultsThe two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS‐R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders.InterpretationOur findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo‐cortico‐basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.
The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.
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