Deep brain stimulation (DBS) in the internal segment of the globus pallidus (GPi) relieves the motor symptoms of Parkinson's disease, yet the mechanism of action remains uncertain. To address the ...question of how therapeutic stimulation changes neuronal firing in the human brain, we studied the effects of GPi stimulation on local neurons in unanesthetized patients. Eleven patients with idiopathic Parkinson's disease consented to participate in neuronal recordings during stimulator implantation surgery. A recording microelectrode and a DBS macroelectrode were advanced through the GPi in parallel until a single neuron was isolated. After a baseline period, stimulation was initiated with varying voltages and different stimulation sites. The intra-operative stimulation parameters (1-8 V, 88-180 Hz, 0.1-ms pulses) were comparable with the postoperative DBS settings. Stimulation in the GPi did not silence local neuronal activity uniformly, but instead loosely entrained firing and decreased net activity in a voltage-dependent fashion. Most neurons had decreased activity during stimulation, although some increased or did not change firing rate. Thirty-three of 45 neurons displayed complex patterns of entrainment during stimulation, and burst-firing was decreased consistently after stimulation. Recorded spike trains from patients were used as input into a model of a thalamocortical relay neuron. Only spike trains that occurred during therapeutically relevant voltages significantly reduced transmission error, an effect attributable to changes in firing patterns. These data indicate that DBS in the human GPi does not silence neuronal activity, but instead disrupts the pathological firing patterns through loose entrainment of neuronal activity.
The health disparities which drive inequities in health outcomes have long plagued our already worn healthcare system and are often dismissed as being a result of social determinants of health. ...Herein, we explore the nature of these inequities by comparing outcomes for racial and ethnic minorities patients suffering from traumatic brain injury (TBI). We retrospectively reviewed all patients enrolled in the Trauma One Database at the Oregon Health & Science University Hospital from 2006 to October 2017 with an abbreviated injury scale (AIS) for the head or neck >2. Racial and ethnic minority patients were defined as non-White or Hispanic. A total of 6,352 patients were included in our analysis with 1,504 in the racial and ethnic minority cohort vs. 4,848 in the non-minority cohort. A propensity score (PS) model was generated to account for differences in baseline characteristics between these cohorts to generate 1,500 matched pairs. The adjusted hazard ratio for in-hospital mortality for minority patients was 2.21 95% Confidence Interval (CI) 1.43-3.41,
< 0.001 using injury type, probability of survival, and operative status as covariates. Overall, this study is the first to specifically look at racial and ethnic disparities in the field of neurosurgical trauma. This research has demonstrated significant inequities in the mortality of TBI patients based on race and ethnicity and indicates a substantive need to reshape the current healthcare system and advocate for safer and more supportive pre-hospital social systems to prevent these life-threatening sequelae.
Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This ...systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters.
Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE RSE). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel.
All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE NORSE). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint.
This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.
Glossopharyngeal neuralgia (GN) is a rare pain condition in which patients experience paroxysmal, lancinating throat pain. Multiple surgical approaches have been used to treat this condition, ...including microvascular decompression (MVD), and sectioning of cranial nerve (CN) IX and the upper rootlets of CN X, or a combination of the two. The aim of this study was to examine the long-term quality of life and pain-free survival after MVD and sectioning of the CN X/IX complex.
A combined retrospective chart review and a quality-of-life telephone survey were performed to collect demographic and long-term outcome data. Quality of life was assessed by means of a questionnaire based on a combination of the Barrow Neurological Institute pain intensity scoring criteria and the Brief Pain Inventory-Facial. Kaplan-Meier analysis was performed to determine pain-free survival.
Of 18 patients with GN, 17 underwent sectioning of the CN IX/X complex alone or sectioning and MVD depending on the presence of a compressing vessel. Eleven of 17 patients had compression of CN IX/X by the posterior inferior cerebellar artery, 1 had compression by a vertebral artery, and 5 had no compression. One patient (6%) experienced no immediate pain relief. Fifteen (88%) of 17 patients were pain free at the last follow-up (mean 9.33 years, range 5.16-13 years). One patient (6%) experienced throat pain relapse at 3 months. The median pain-free survival was 7.5 years ± 10.6 months. Nine of 18 patients were contacted by telephone. Of the 17 patients who underwent sectioning of the CN IX/X complex, 13 (77%) patients had short-term complaints: dysphagia (n = 4), hoarseness (n = 4), ipsilateral hearing loss (n = 4), ipsilateral taste loss (n = 2), and dizziness (n = 2) at 2 weeks. Nine patients had persistent side effects at latest follow-up. Eight of 9 telephone respondents reported that they would have the surgery over again.
Sectioning of the CN IX/X complex with or without MVD of the glossopharyngeal nerve is a safe and effective surgical therapy for GN with initial pain freedom in 94% of patients and an excellent long-term pain relief (mean 7.5 years).
Despite rapid development and expansion of neuromodulation technologies, knowledge about device and/or therapy durability remains limited. The aim of this study was to evaluate the long-term rate of ...hardware and therapeutic failure of implanted devices for several neuromodulation therapies.
The authors performed a retrospective analysis of patients' device and therapy survival data (Kaplan-Meier survival analysis) for deep brain stimulation (DBS), vagus nerve stimulation (VNS), and spinal cord stimulation (SCS) at a single institution (years 1994-2015).
During the study period, 450 patients underwent DBS, 383 VNS, and 128 SCS. For DBS, the 5- and 10-year initial device survival was 87% and 73%, respectively, and therapy survival was 96% and 91%, respectively. For VNS, the 5- and 10-year initial device survival was 90% and 70%, respectively, and therapy survival was 99% and 97%, respectively. For SCS, the 5- and 10-year initial device survival was 50% and 34%, respectively, and therapy survival was 74% and 56%, respectively. The average initial device survival for DBS, VNS, and SCS was 14 years, 14 years, and 8 years while mean therapy survival was 18 years, 18 years, and 12.5 years, respectively.
The authors report, for the first time, comparative device and therapy survival rates out to 15 years for large cohorts of DBS, VNS, and SCS patients. Their results demonstrate higher device and therapy survival rates for DBS and VNS than for SCS. Hardware failures were more common among SCS patients, which may have played a role in the discontinuation of therapy. Higher therapy survival than device survival across all modalities indicates continued therapeutic benefit beyond initial device failures, which is important to emphasize when counseling patients.
Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal ...(emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.
•We reported a first-in-human application of responsive deep brain stimulation for OCD•The area-based feature triggered closed-loop stimulation to ameliorate OCD symptoms•We identified an association between NAc-VeP low-frequency oscillatory power and OCD•We provided a concept for a personalized, physiologically guided DBS strategy for OCD
We report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for treatment-refractory OCD. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion.
Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The ...first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that DOX administration caused marked histological alterations of widespread inflammation and tubular degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65 (NF-κB/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1beta (IL-1β), 8-hydroxy-2' -deoxyguanosine (8-OHdG), and Beclin-1 in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly, Met could minimize all histopathological changes as well as the disruptions caused by DOX in the aforementioned measures. Thus, Met provided a workable method for suppressing the nephrotoxicity that occurred during the DOX regimen via the deactivation of the Beclin-1/LC3B pathway.
Idiopathic intracranial hypertension (IIH) is characterized by headaches, visual obscurations, and papilledema, and the diagnosis involves lumbar puncture (LP) with an elevated opening pressure (OP) ...≥20 cm H20. When papilledema is absent, the diagnosis becomes less clear. Some physicians have argued that the absence of papilledema rules out IIH, whereas others maintain that elevated OP is sufficient for diagnosis.
The authors performed a single-institution 4-year retrospective analysis of patients who underwent invasive intracranial pressure (ICP) monitoring for presumed IIH.
A total of 22 patients were reviewed, and 13 had classic symptoms of IIH, documented elevated OP, and absence of papilledema; 5/13 (38%) patients had proven intracranial hypertension as shown by invasive ICP monitoring, whereas 8/13 (62%) had normal ICP.
With the use of current diagnostic algorithms of clinical presentation and elevated OP, over half of patients without papilledema in our series would be falsely diagnosed with IIH, which could result in unnecessary medical and surgical intervention. Thus, elevated OP as determined by LP is insufficient to diagnose IIH. On the other hand, the absence of papilledema does not rule out intracranial hypertension.
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