Hippocampus diffusivity abnormalities in classical trigeminal neuralgia.

Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Brain imaging signatures of neuropathic facial pain derived by artificial intelligence.

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients' symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups-the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain.

Newly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation.

Here, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

Pre-motor versus motor cerebral cortex neuromodulation for chronic neuropathic pain.

Electrical stimulation of the cerebral cortex (ESCC) has been used to treat intractable neuropathic pain for nearly two decades, however, no standardized approach for this technique has been developed. In order to optimize targeting and validate the effect of ESCC before placing the permanent grid, we introduced initial assessment with trial stimulation, using a temporary grid of subdural electrodes. In this retrospective study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target-optimization for ESCC. Location of the temporary grid electrodes and location of permanent electrodes were evaluated in correlation with the long-term efficacy of ESCC. The results of this study demonstrate that the long-term effect of subdural pre-motor cortex stimulation is at least the same or higher compare to effect of subdural motor or combined pre-motor and motor cortex stimulation. These results also demonstrate that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target that is critical in cases when brain shift is expected. Proposed methodology and novel results open a new direction for development of neuromodulation techniques to control chronic neuropathic pain.

Segment-Specific Orientation of the Dorsal and Ventral Roots for Precise Therapeutic Targeting of Human Spinal Cord.

OBJECTIVE: To provide precise description of the dorsal and ventral roots orientation along with the main spinal cord anatomical measurements and their segment-specific variations. PATIENTS AND METHODS: We collected and analyzed the measurements of the spines, spinal cords, and dorsal and ventral roots (C2-L5) of nine adult cadavers (five males and four females). RESULTS: This study for the first time provides analysis of the dorsal and ventral roots orientation along with spinal cord anatomical measurements and their segment-specific distribution. The results of this study showed less variability in rostral root angles compared with the caudal. Dorsal and ventral rootlets were oriented mostly perpendicular to the spinal cord at the cervical level and had more parallel orientation to the spinal cord at the thoracic and lumbar segments. The number of rootlets per root was greatest at dorsal cervical and lumbar segments. Spinal cord transverse diameter and width of the dorsal columns were largest at cervical segments. The strongest correlation between the spinal cord and vertebrae structures was found between the length of intervertebral foramen to rostral rootlet distance and vertebral bone length. CONCLUSION: These results demonstrate consistent variation in spinal cord anatomical features across all tested subjects. The results of this study can be used to locate spinal roots and main spinal cord landmarks based on bone marks on computed tomography or X-rays. These results could improve stereotactic surgical procedures and electrode positioning for neuromodulation procedures.