Miller, Kai J.

Abstract Background Deep brain stimulator (DBS)–related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9–6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Abstract Surgery can cure or significantly improve both the frequency and the intensity of seizures in patients with medication‐refractory epilepsy. The set of diagnostic and therapeutic interventions involved in the path from initial consultation to definitive surgery is complex and includes a multidisciplinary team of neurologists, neurosurgeons, neuroradiologists, and neuropsychologists, supported by a very large epilepsy‐dedicated clinical architecture. In recent years, new practices and technologies have emerged that dramatically expand the scope of interventions performed. Stereoelectroencephalography has become widely adopted for seizure localization; stereotactic laser ablation has enabled more focal, less invasive, and less destructive interventions; and new brain stimulation devices have unlocked treatment of eloquent foci and multifocal onset etiologies. This article articulates and illustrates the full framework for how epilepsy patients are considered for surgical intervention, with particular attention given to stereotactic approaches.

OBJECTIVE One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients’ skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = −0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = −0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Abstract Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

Abstract Only recently has the rodent hippocampus been implicated in orexigenic appetitive processing1,2. This function has been found to be mediated at least in part by lateral hypothalamic inputs involving an orexigenic neuropeptide, melanin-concentrating hormone3. This circuit remains elusive in humans. Here, we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues and this modulation was specific to the dorsolateral hippocampus. Lastly, structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behavior revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

OBJECTIVE The prevalence of epilepsy in the older adult population is increasing. While surgical intervention in younger patients is supported by level I evidence, the safety and efficacy of epilepsy surgery in older individuals is less well established. The aim of this study was to evaluate seizure freedom rates and surgical outcomes in older epilepsy patients. METHODS The authors’ institutional electronic database was queried for patients older than 50 who had undergone epilepsy surgery during 2002–2018. Cases were grouped into 50–59, 60–69, and 70+ years old. Seizure freedom at the last follow-up constituted the primary outcome of interest. The institutional analysis was supplemented by a literature review and meta-analysis (random effects model) of all published studies on this topic as well as by an analysis of complication rates, mortality rates, and cost data from a nationwide administrative database (Vizient Inc., years 2016–2019). RESULTS A total of 73 patients (n = 16 for 50–59 years, n = 47 for 60–69, and n = 10 for 70+) were treated at the authors’ institution. The median age was 63 years, and 66% of the patients were female. At a median follow-up of 24 months, seizure freedom was 73% for the overall cohort, 63% for the 50–59 group, 77% for the 60–69 group, and 70% for the 70+ group. The literature search identified 15 additional retrospective studies (474 cases). Temporal lobectomy was the most commonly performed procedure (73%), and mesial temporal sclerosis was the most common pathology (52%), followed by nonspecific gliosis (19%). The pooled mean follow-up was 39 months (range 6–114.8 months) with a pooled seizure freedom rate of 65% (95% CI 59%–72%). On multivariable meta-regression analysis, an older mean age at surgery (coefficient [coeff] 2.1, 95% CI 1.1–3.1, p < 0.001) and the presence of mesial temporal sclerosis (coeff 0.3, 95% CI 0.1–0.6, p = 0.015) were the most important predictors of seizure freedom. Finally, analysis of the Vizient database revealed mortality rates of 0.5%, 1.1%, and 9.6%; complication rates of 7.1%, 10.1%, and 17.3%; and mean hospital costs of $31,977, $34,586, and $40,153 for patients aged 50–59, 60–69, and 70+ years, respectively. CONCLUSIONS While seizure-free outcomes of epilepsy surgery are excellent, there is an expected increase in morbidity and mortality with increasing age. Findings in this study on the safety and efficacy of epilepsy surgery in the older population may serve as a useful guide during preoperative decision-making and patient counseling.

AbstractThere is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power‐in‐band [PIB]), recorded in 10‐min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB‐based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist‐confirmed Hc seizures, and assessed by area under the precision‐recall curve (PR‐AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1–4. The best detector had 7‐Hz center frequency, 5‐Hz band width, and 10‐s epoch duration (group PR‐AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.

BACKGROUND Open surgical treatment of insular epilepsy holds particular risk of injury to middle cerebral artery branches, the operculum (through retraction), and adjacent language-related white matter tracts in the language-dominant hemisphere. Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (LITT) is a surgical alternative that allows precise lesioning with potentially less operative risk. The authors presented the case of a 13-year-old girl with intractable, MRI-negative, left (dominant hemisphere) insular epilepsy that was treated with LITT. Diffusion tensor imaging (DTI) tractography was used to aid full posterior insular lesioning in the region of stereo electroencephalography–determined seizure onset while avoiding thermal injury to the language-related superior longitudinal fasciculus (SLF)/arcuate fasciculus (AF) and inferior fronto-occipital fasciculus (IFOF). OBSERVATIONS DTI tractography was used successfully in planning insular LITT and facilitated a robust insular ablation with sharp margins at the interfaces with the SLF/AF and IFOF. These tracts were spared, and no neurological deficits were induced through LITT. LESSONS Although it is technically demanding and has important limitations that must be understood, clinically available DTI tractography adds precision and confidence to insular laser ablation when used to protect important language-related white matter tracts.