Andre Guelman Machado

Many people with Parkinson’s disease (PwPD) lack optimal care due to limited access to neurologists and a reliance on subjective rating scales for treatment decisions. The Ceraxis Insight platform was designed to provide quantitative measures of the cardinal motor symptoms of Parkinson’s disease (PD) through self-administered assessments performed using a tablet paired with a sensor-embedded stylus. The aim of this study was to assess the validity of the Ceraxis Insight outcome metrics against clinical gold-standard measures of PD motor symptoms. Nineteen PwPD completed a clinical examination and the nine Ceraxis Insight assessment modules. Quantitative performance metrics were calculated from the platform’s IMU, force transducer, and touchscreen inputs. Mixed-effect models and correlation analyses determined that multiple quantitative metrics from the Ceraxis Insight modules significantly predicted (p < 0.05) and were significantly correlated (correlation coefficients > 0.70) with the MDS-UPDRS III total score, bradykinesia, tremor, rigidity, and postural instability and gait difficulty sub-scores. Logistic regression models determined that multiple Ceraxis Insight metrics discriminated between ON- and OFF-deep brain stimulation (DBS) conditions, with Area Under the Receiver Operating Characteristic Curve (AUC) values exceeding 0.70. The Ceraxis Insight platform provides a validated, objective assessment of PD motor symptoms that may be performed within clinical or remote settings for data-driven evaluation and treatment.

BACKGROUND AND OBJECTIVES: Our group recently completed a trial of deep brain stimulation targeting the dentate nucleus in patients with poststroke hemiparesis. Although accurate, we found significant limitations to the Leksell G frame (Elekta) for posterior fossa stereotaxis. In this study, we assess the feasibility and accuracy of a commercially available custom-built stereotactic platform for posterior fossa targeting. The smaller profile of these devices, compared with conventional stereotactic headframe make it a promising alternative when surgical access is limited. METHODS: Three anthropomorphic phantom models with posterior fossa targets marked by nylon screws were used. Each skull had a unique 4-legged microplatform designed from their fiducial location, target, and trajectory plans. We simulated posterior fossa stereotactic cannulation in the neurosurgical OR using standard equipment. Accuracy was evaluated by the deviation of the final cannula placement from the planned target and entry. RESULTS: The Euclidean distance between planned target and final cannula tip position ranged between 0.4 mm (skull 3) and 1.29 mm (skull 1). The mean target deviation from plan was 0.93 mm (SD ± 0.4 mm). The mean entry deviation from plan was 0.9 mm (SD ± 0.6 mm). The mean sagittal and coronal trajectory angulation error were 0.73° (SD ± 0.4°) and 0.04° (SD ± 0.02°), respectively. CONCLUSION: In this in vitro study, our data show that 3-dimensional printed, custom-made, single-use platforms may be feasible and accurate for posterior fossa stereotactic surgery. Further investigation with in vivo studies will be necessary to assess clinical practicality and accuracy in vivo.

The cerebellum acts as a forward internal model to predict motor outcomes, compare them with sensory feedback, and generate prediction errors that refine prediction accuracy. Our physiological understanding of cerebellar function during motor control derives predominantly from animal experiments and clinical observations in patients with disorders of the cerebellum or its connections with the cerebrum and spinal cord. Here, we report a human electrophysiology‐based investigation of cerebello‐thalamo‐cortical pathway activity during motor error detection and correction. Participants performed a computerized motor oddball task while synchronized electrophysiological recordings were collected from cerebellar dentate (DN) using depth electrodes and scalp electroencephalography (EEG). The task involved moving a 2‐D ball on a screen toward a predetermined target at 40% (standard trials) or 20% (oddball trials) of their maximum voluntary contraction. Six participants completed an average of 239 trials, with oddball trials randomly occurring with a 30% frequency. At the cortex, oddball trials exhibited significantly greater centro‐parietal error positivity and fronto‐centro‐parietal desynchronization during error correction, predominantly in the alpha and low beta frequency bands. DN examination also revealed greater alpha and low beta desynchronization during error correction. Lastly, oddball trials showed significantly greater cortico‐cerebellar coherence during error correction in the same frequency bands with bidirectional interaction between the cortex and DN. These findings expand on the cortico‐cerebello‐cortical physiology of human motor control and provide cues for designing interventions aimed at alleviating the functional burdens of acquired injuries of the central nervous system.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) is an established neurosurgical treatment of a variety of neurological disorders. DBS is considered a safe and effective neurosurgical procedure; however, surgical complications are inevitable, and clinical outcomes may vary. The aim of this study was to describe DBS complications at a large clinical center in the United States and to investigate the relationship between patients' baseline characteristics, surgical technique, and operative complications. METHODS: We identified all patients who underwent DBS lead implantation at our center between 1st January 2012 and 1st January 2020. We extracted relevant information regarding patient demographics, surgical details, clinical complications, and clinical outcomes from the electronic medical records. RESULTS: A total of 859 leads were implanted in 481 patients (153 men, 328 women). The mean patient age at the time of the surgery was 65 years, with the mean disease duration of 13.3 years. There were no mortalities and 57 readmissions within 30 days (mean = 14.2 days). The most common complications included pneumocephalus (n = 661), edema (n = 78), altered mental state (n = 35), implantable pulse generator discomfort (n = 34), hemorrhage (n = 26), and infection (n = 23). Most notably, the use of general anesthesia, hypertension, heart disease, and depression were associated with significantly longer postoperative stay. High preoperative body mass index was associated with higher rates of surgery-related infections and lead revision/explantation. The intraoperative mean arterial pressure, anesthesia type, and frame apparatus were all important predictors of postoperative pneumocephalus. CONCLUSION: In this report, we described the rates and types of complications associated with DBS surgery at a large neurosurgical center in the United States. The novel insights highlighted in this study present an opportunity to further improve the clinical outcomes and patient selection in DBS surgery.

While ipsilesional cortical electroencephalography has been associated with poststroke recovery mechanisms and outcomes, the role of the cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that poststroke motor control relies on increased corticocerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting poststroke motor rehabilitation. We investigated the excitability of the ipsilesional cortex, the dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, 10 human participants (two women) at the end of 4–8 months of DN deep brain stimulation (DBS) showed (1) significantly improved motor control indexed by computerized motor tasks; (2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and (3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the poststroke state and its connectivity with the ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of corticocerebellar-cortical network after stroke and its modulation by DN-DBS.

OBJECTIVE: High accuracy and precision are essential in stereotactic neurosurgery, as targeting errors can significantly affect clinical outcomes. Image registration is a vital step in stereotaxis, and understanding the error associated with different image registration methods is important to inform the choice of equipment and techniques in stereotactic neurosurgery. The authors aimed to quantify the test-retest reliability and stereotactic accuracy of cone-beam CT (CBCT) compared with the current clinical gold-standard technique (i.e., CT). METHODS: Two anthropomorphic phantom models with 40 independent unique steel spheres were developed to compare CBCT frame and stereotactic space registration with the clinical gold standard (CT). The cartesian coordinates of each sphere were compared between the imaging modalities for test-retest reliability and overall accuracy. RESULTS: Both imaging modalities showed similar levels of fiducial deviation from the expected geometry. The equivalence test demonstrated mean differences between CT and CBCT registration of −0.082 mm (90% CI −0.27 to 0.11), −0.045 mm (90% CI −0.43 to 0.34), and −0.041 mm (90% CI −0.064 to 0.018) for coordinates in the x-, y-, and z-axes, respectively. The mean euclidean distance difference between the two modalities was 0.28 mm (90% CI 0.27–0.29). CONCLUSIONS: Accuracy and precision were comparable between CBCT and CT image registrations. These findings suggest that CBCT registration can be used as a clinically equivalent substitute to gold-standard CT acquisition.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract. Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test. All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases. CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery. ClinicalTrials.gov identifier: NCT02881151.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1–3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Background: Deep brain stimulation (DBS) is a neurosurgical treatment used for the treatment of movement disorders. Surgical and perioperative complications, although infrequent, can result in clinically significant neurological impairment. Objectives: In this study, we evaluated the incidence and risk factors of intracranial bleeding in DBS surgery. Method: Medline, EMBASE, and Cochrane were screened in line with PRISMA 2020 guidelines to capture studies reporting on the incidence of hemorrhagic events in DBS. After removing duplicates, the search yielded 1,510 papers. Abstracts were evaluated by two independent reviewers for relevance. A total of 386 abstracts progressed to the full-text screen and were assessed against eligibility criteria. A total of 151 studies met the criteria and were included in the analysis. Any disagreement between the reviewers was resolved by consensus. Relevant data points were extracted and analyzed in OpenMeta [Analyst] software. Results: The incidence of intracranial bleeding was 2.5% (95% CI: 2.2–2.8%) per each patient and 1.4% (95% CI: 1.2–1.6%) per each implanted lead. There was no statistically significant difference across implantation targets and clinical indications. Patients who developed an intracranial bleed were on average 5 years older (95% CI: 1.26–13.19), but no difference was observed between the genders (p = 0.891). A nonsignificant trend was observed for a higher risk of bleeding in patients with hypertension (OR: 2.99, 95% CI: 0.97–9.19) (p = 0.056). The use of microelectrode recording did not affect the rate of bleeding (p = 0.79). Conclusions: In this review, we find that the rate of bleeding per each implanted lead was 1.4% and that older patients had a higher risk of hemorrhage.