Deep brain stimulation of the central thalamus restores arousal and motivation in a zolpidem-responsive patient with akinetic mutism after severe brain injury

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness

Could deep brain stimulation be a possible solution for acquired hypothalamic obesity?

OBJECTIVE: Hypothalamic dysfunction may result in morbid obesity as a consequence of decreased energy expenditure, decreased feelings of satiety, and increased fat storage. In patients with hypothalamic dysfunction, neurobehavioral dysfunction is also often present. Currently, no effective treatment has been found for hypothalamic obesity (HO). We hypothesize that deep brain stimulation (DBS) may be an effective treatment for patients with hypothalamic dysfunction, aiming to treat HO as well as the neurobehavioral dysfunction. METHODS: A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases for studies published until May 2022 reporting on DBS for the treatment of HO. RESULTS: Three studies met the predetermined inclusion criteria, with in total six patients treated with DBS for HO, of which five patients with Prader-Willi syndrome (PWS) and one patient with HO after treatment for craniopharyngioma (CP). Targets of DBS included the lateral hypothalamic area (LHA) and the nucleus accumbens (NAcc). In patients with PWS, LHA-DBS was associated with a mean increase of Body Mass Index (BMI) (+5.8%), with no change in hormonal levels, results of blood workup, sleep, or neuropsychological evaluation. In the patient with CP, NAcc-DBS was associated with a decrease in BMI (-8.7%) and a subjective increase in mental health, energy and willingness to act, and no feeling of increased appetite. No objective measurements on neurobehavioral function were reported. No severe adverse events were reported in these cases. Mild to moderate adverse events included hypomanic symptoms and infection. All patients with a described follow-up period ( n = 5) were able to sustain the treatment for at least 6 months with few interruptions. CONCLUSION: There is limited research reporting on DBS for HO. The effectiveness differed across studies and the evidence is limited. Although there may be potential for DBS treatment in the severe-refractory condition of HO in patients with CP, more research is needed for target selection and evaluation of effectiveness

Long-term experience with intraoperative microrecording during DBS neurosurgery in STN and GPi

Intraoperative microelectrode recording (MER) for targeting during deep brain stimulation (DBS) procedures has been evaluated over a period of 4 years, in 57 consecutive patients with Parkinson's disease, who received DBS in the subthalamic nucleus (STN-DBS), and 28 consecutive patients with either dystonia (23) or Parkinson's disease (five), in whom the internal segment of the globus pallidus (GPi-DBS) was targeted. The procedure for DBS was a one-stage bilateral stereotactic approach using a combined electrode for both MER and macrostimulation. Up to five micro/macro-electrodes were used in an array with a central, lateral, medial, anterior, and posterior position. Final target location was based on intraoperative test stimulation. For the STN, the central trajectory was chosen for implantation in 50% of the cases and for the globus pallidus internus (GPi) in 57% of the cases. Furthermore, in 64% of the cases, the channel selected for the permanent electrode corresponded with the trajectory having the longest segment of STN MER activity. For the GPi, this was the case in 61%. The mean and standard deviation of the deepest contact point with respect to the magnetic resonance imaging (MRI)-based target for the STN was 2.1 +/- 1.5 mm and for the GPi was -0.5 +/- 1.2 mm. MER facilitates the selection of the final electrode location in STN-DBS and GPi-DBS, and based on the observed MER activity, a pre-selection could be made as to which channel would be the best candidate for macro-test stimulation and at which depth should be stimulated. The choice of the final location is based on intraoperative test stimulation, and it is demonstrated that regularly it is not the central channel that is chosen for implantation. On average, the target as defined by MER activity intensity was in accordance with the MRI-based targets both for the STN and GPi. However, the position of the best MER activity did not necessarily correlate with the locus that produced the most beneficial clinical response on macroelectrode testing intraoperativel

Treatment of electrical status epilepticus in sleep : A pooled analysis of 575 cases

OBJECTIVE: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome. METHODS: A literature search using PubMed and Embase was performed. Articles were selected that contain original treatment data of patients with ESES syndrome. Authors were contacted for additional information. Individual patient data were collected, coded, and analyzed using logistic regression analysis. The three predefined main outcome measures were improvement in cognitive function, electroencephalography (EEG) pattern, and any improvement (cognition or EEG). RESULTS: The literature search yielded 1,766 articles. After applying inclusion and exclusion criteria, 112 articles and 950 treatments in 575 patients could be analyzed. Antiepileptic drugs (AEDs, n = 495) were associated with improvement (i.e., cognition or EEG) in 49% of patients, benzodiazepines (n = 171) in 68%, and steroids (n = 166) in 81%. Surgery (n = 62) resulted in improvement in 90% of patients. In a subgroup analysis of patients who were consecutively reported (585 treatments in 282 patients), we found improvement in a smaller proportion treated with AEDs (34%), benzodiazepines (59%), and steroids (75%), whereas the improvement percentage after surgery was preserved (93%). Possible predictors of improved outcome were treatment category, normal development before ESES onset, and the absence of structural abnormalities. SIGNIFICANCE: Although most included studies were small and retrospective and their heterogeneity allowed analysis of only qualitative outcome data, this pooled analysis suggests superior efficacy of steroids and surgery in encephalopathy with ESES

Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study

Background: Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiology of AN.  Methods: We performed functional MRI on four AN patients that participated in a pilot study on the efficacy, safety, and functional effects of DBS targeted at the ventral limb of the capsula interna (vALIC). The patients and six gender-matched healthy controls (HC) were investigated at three different time points. We used an adapted version of the monetary incentive delay task to probe generic reward processing in patients and controls, and a food-specific task in patients only.  Results: At baseline, no significant differences for reward anticipation were found between AN and HC. Significant group (AN and HC) by time (pre- and post-DBS) interactions were found in the right precuneus, right putamen, right ventral and medial orbitofrontal cortex (mOFC). No significant interactions were found in the food viewing task, neither between the conditions high-calorie and low-calorie food images nor between the different time points. This could possibly be due to the small sample size and the lack of a control group.  Conclusion: The results showed a difference in the response of reward-related brain areas post-DBS. This supports the hypotheses that the reward circuitry is involved in the pathogenesis of AN and that DBS affects responsivity of reward-related brain areas. Trial registration Registered in the Netherlands Trial Register (https://www.trialregister.nl/trial/3322 ): NL3322 (NTR3469)