Anatomical Parcellations of Brodmann's Areas 4 and 6: A Study on Cortical Thickness for Improved Neurosurgical Planning.

The cerebral cortex, comprising six layers known as the neocortex, is a sheet of neural tissue that contains regions for neurosurgical planning, including the primary motor cortex (PMC), the supplementary motor cortex (SMA), and the primary somatosensory cortex (PSC). However, knowledge gaps persist concerning the transition points between areas 3 to 4 and 4 to 6 and the SMA's extent. This study aims to develop a non-invasive protocol using T1/T2 weighted imaging to identify crucial anatomic borders around the primary and supplementary motor cortex for neurosurgical planning. A comprehensive literature search on the cytoarchitectonic borders of Brodmann's areas 3a, 4, and 6 was conducted, and relevant articles were selected based on their examination of these borders. The primary motor cortex was found to be the thickest region in the human brain, with discernible differences in thickness between areas 4 and 6. T2-weighted images revealed significant cortical thickness differences between the precentral and postcentral gyrus. Various methods have been employed to parcellate borders between cortical regions, including Laplace's equation and equi-volume models. A triple-layer appearance in the primary motor cortex and a novel method based on myelin content demonstrated consistent agreements with historically defined cytoarchitectonic borders. However, differentiating areas 4 and 6 from MR imaging remains challenging. Recent studies suggest potential methods for pre-surgically identifying the primary motor cortex and examining differences in cortical thickness in diseases. A protocol should be established to guide neurosurgeons in accurately identifying areas 4 and 6, possibly using imaging modalities superimposed on myelin maps for differentiation and determining area 6's anterior extent.

Glioma Metabolic Feedback In Situ: A First-In-Human Pharmacodynamic Trial of Difluoromethylornithine + AMXT-1501 Through High-Molecular Weight Microdialysis.

BACKGROUND AND OBJECTIVES: No new drug has improved survival for glioblastoma since temozolomide in 2005, due in part to the relative inaccessibility of each patient's individualized tumor biology and its response to therapy. We have identified a conserved extracellular metabolic signature of enhancing high-grade gliomas enriched for guanidinoacetate (GAA). GAA is coproduced with ornithine, the precursor to protumorigenic polyamines through ornithine decarboxylase (ODC). AMXT-1501 is a polyamine transporter inhibitor that can overcome tumoral resistance to the ODC inhibitor, difluoromethylornithine (DFMO). We will use DFMO with or without AMXT-1501 to identify candidate pharmacodynamic biomarkers of polyamine depletion in patients with high-grade gliomas in situ . We aim to determine (1) how blocking polyamine production affects intratumoral extracellular guanidinoacetate abundance and (2) the impact of polyamine depletion on the global extracellular metabolome within live human gliomas in situ. METHODS: DFMO, with or without AMXT-1501, will be administered postoperatively in 15 patients after clinically indicated subtotal resection for high-grade glioma. High-molecular weight microdialysis catheters implanted into residual tumor and adjacent brain will be used for postoperative monitoring of extracellular GAA and polyamines throughout therapeutic intervention from postoperative day (POD) 1 to POD5. Catheters will be removed on POD5 before discharge. EXPECTED OUTCOMES: We anticipate that GAA will be elevated in tumor relative to adjacent brain although it will decrease within 24 hours of ODC inhibition with DFMO. If AMXT-1501 effectively increases the cytotoxic impact of ODC inhibition, we expect an increase in biomarkers of cytotoxicity including glutamate with DFMO + AMXT-1501 treatment when compared with DFMO alone. DISCUSSION: Limited mechanistic feedback from individual patients' gliomas hampers clinical translation of novel therapies. This pilot Phase 0 study will provide in situ feedback during DFMO + AMXT-1501 treatment to determine how high-grade gliomas respond to polyamine depletion.

Brain Metabolic Changes with Longitudinal Transcutaneous Afferent Patterned Stimulation in Essential Tremor Subjects.

Background: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor (ET) subjects. However, the mechanism of action of TAPS is unknown. Here, we investigated changes in brain metabolism over three months of TAPS use in ET subjects. Methods: This was an interventional, open label, single group study enrolling 5 ET subjects. They received 40 minutes of TAPS treatment twice daily for 90 days. Brain metabolic activity and tremor severity were measured using 18F-fluorodeoxyglucose (FDG) PET/CT, and the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), respectively, at baseline and after 90 days. Tremor power and frequency was measured before and after all TAPS sessions using an onboard three-axis accelerometer. Results: FDG PET/CT revealed areas of hypermetabolism in ipsilateral cerebellar hemisphere and hypometabolism in contralateral cerebellar hemisphere following 90 days of TAPS treatment, compared to day one (uncorrected p value <0.05). Paired pre-post kinematic measurements over 90 days showed significantly decreased tremor power (p < 0.0001) but no change in tremor frequency. The TETRAS score on day 1 decreased from 6.5 ± 2.5 to 4.1 ± 1.8 following TAPS (p = 0.05). The pre-post TETRAS scores on day 90: 4.9 ± 1.5 and 4.1± 1 were lower than pre-TAPS TETRAS score on day 1 (p = 0.14 and 0.05, respectively). Conclusions: Our results suggest that longitudinal TAPS of the median and radial nerves modulates brain metabolism in areas instrumental to motor coordination and implicated in ET. Clinically, TAPS reduced tremor power, but had no effect on tremor frequency. This study paves the way for comprehensive studies in larger cohorts to further elucidate the mechanism of TAPS. Highlights: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor subjects. Longitudinal TAPS therapy alters cerebellar metabolism, which can be a cause or consequence of tremor reduction. Cerebellar-premotor region connectivity may play a role in the anti-tremor effects of TAPS.

Geriatrics Education Team Model Results in Sustained Geriatrics Training in 15 Residency and Fellowship Programs and Scholarship.

Caring for the growing elderly population will require specialty and subspecialty physicians who have not completed geriatric medicine fellowship training to participate actively in patient care. To meet this workforce demand, a sustainable approach to integrating geriatrics into specialty and subspecialty graduate medical education training is needed. This article describes the use of a geriatrics education team (GET) model to develop, implement, and sustain specialty-specific geriatrics curricula using a systematic process of team formation and needs assessment through evaluation, with a unique focus on developing curricular interventions that are meaningful to each specialty and satisfy training, scholarship, and regulatory requirements. The GET model and associated results from 15 specialty residency and fellowship training programs over a 4-year period include 93% curriculum sustainability after initial implementation, more than half of the programs introducing additional geriatrics education, and more than 80% of specialty GETs fulfilling their scholarship requirements through their curriculum dissemination. Win-wins and barriers encountered in using the GET model, along with the model's efficacy in curriculum development, sustainability, and dissemination, are summarized.

Shoulder symptoms and function in geriatric patients.

BACKGROUND AND PURPOSE: Musculoskeletal problems, including shoulder pain, are common in the general population and are often cited as reasons for physician visits. Although many risk factors for shoulder pain are postulated, the effects of shoulder pain on functional level and perceived quality of life are poorly characterized in older adults. In this study, we set out to determine the prevalence and impact of shoulder symptoms and dysfunction in an older adult veteran population. METHODS: A chart review, cross-sectional survey, and examination were performed. A sample of 93 individuals, aged 60 years or older, was recruited from a primary clinic outpatient waiting room at the Clement J. Zablocki VA Medical Center in Milwaukee, Wisconsin. Patients were asked about shoulder symptoms and self-assessed health and completed the Stanford Modified Health Assessment Questionnaire. A series of 3 shoulder maneuvers was used to assess shoulder mobility and pain. The presence of diabetes and statin use was documented. A more thorough chart review was performed on individuals who reported shoulder pain and disability. RESULTS: Severe shoulder pain was common in the study group, reported by 31% of all participants. Functional limitation measured by the Modified Health Assessment Questionnaire and answering "yes" to greater difficulty performing daily tasks was associated with reduced internal rotation, which was present in almost 36% of all participants. Symptoms were often bilateral. No statistically significant risk factors emerged in this small sample, but suggestive trends were apparent. Interestingly, few patients reported discussing these problems with their providers, and shoulder-related problems were documented in only 10% of corresponding problem lists of symptomatic patients. CONCLUSIONS: With an aging population, the high prevalence of shoulder pain may have considerable impact on public health. It will become increasingly important to define risk factors, delineate etiologies, and devise new management strategies for patients with symptomatic shoulder disease.