Retinal capillary plexus in Parkinson's disease using optical coherence tomography angiography.

AIM: To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson's disease (PD) using optical coherence tomography angiography (OCT-A). METHODS: A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens, "Georgios Gennimatas" from March 2021 to March 2022 was conducted. Totally 44 patients with PD were included and 18 healthy controls were examined, hence a total of 124 eyes were enrolled in the study. The foveal and parafoveal superficial and deep capillary plexus vascular density (fSCP-VD, fDCP-VD, pSCP-VD, pDCP-CD) and foveal avascular zone (FAZ) were quantified with OCTA. Optical coherence tomography (OCT) was used to measure macular thickness. Our statistical analysis was conducted by using a mixed effect linear regression model. RESULTS: After adjustment for age and gender, the mean parafoveal superficial capillary plexus vascular density (pSCP-VD) and mean parafoveal deep capillary plexus vascular density (pDCP-VD) were significantly decreased in individuals with PD (P<0.001 in both) by -2.35 (95%CI -3.3, -1.45) and -7.5 (95%CI -10.4, -4.6) respectively. fSCP-VD and fDCP-VD didn't approach statistical significance. The FAZ area and perimeter were significantly decreased (P<0.001 in both) by -0.1 mm2 (95%CI -0.13, -0.07) and -0.49 mm2 (95%CI -0.66, -0.32) respectively. Circularity didn't approach statistical significance. Central retinal thickness (CRT) was significantly decreased in individuals with PD (P<0.001) by -23.1 µm (95%CI -30.2, -16) and temporal retinal thickness (TRT) was decreased (P=0.025) by -11 µm (95%CI -22, -1.5) while nasal retinal thickness (NRT) only approached statistical significance (P=0.066). CONCLUSION: The mean pSCP-VD, pDCP-VD, CRT and TRT are significantly decreased and FAZ is altered in individuals with PD. These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Neglected Rupture of the Patellar Tendon After Fixation of Tibial Tubercle Avulsion in an Adolescent Male Managed With Ipsilateral Semitendinosus Autograft Reconstruction.

The combination of a tibial tubercle fracture with patellar tendon avulsion in adolescents is an extremely rare injury that needs to be managed properly. Herein, we report the case of a 15-year-old boy who presented to our department two months after sustaining a tibial tubercle fracture that had been managed with mini-open reduction and internal fixation in another hospital; he had restricted range of motion and complete inability to extend his knee. Clinical and radiological investigations revealed a neglected avulsion of the patellar tendon with marked scarring and severe retraction. The patient underwent patellar tendon reconstruction using the ipsilateral semitendinosus tendon that passed through separate tunnels in the patella and proximal tibia. The postoperative course was uneventful, and one year later the patient had a satisfactory range of motion and a Lysholm score of 90. To our knowledge, a neglected patellar tendon avulsion after tibial tubercle fracture fixation has been reported only once in the literature. The reconstruction of the patellar tendon using an ipsilateral semitendinosus autograft is an excellent surgical technique, especially when severe tendon retraction has occurred.

Does Cozen's phenomenon warrant surgical intervention?

PURPOSE: Proximal tibial metaphyseal fractures can be complicated by a late valgus deformity, referred to as Cozen's phenomenon. We studied children with such fractures to determine whether the child's age at the time of injury influenced the development of Cozen's as well as the occurrence of elongation. In addition, we explored whether the deformity resolved at long-term follow-up. METHODS: We conducted a retrospective study of 33 patients (six months to 14 years old). Mean follow-up was 8.8 years (3 to 25). We measured angulation of the fractured limb post-treatment, at maximum deformity and final follow-up, as well as elongation and compared them with the uninjured limb. RESULTS: Three of the fractures were treated surgically whereas the rest, nonoperatively. In all, 15 out of 33 fractures developed late valgus deformity between eight and 19 months (mean time 12.5 months). A total of 24 fractures developed elongation. We found no association of either of these with age. Angulation increased to a statistically significant level, from post-treatment to maximum deformity, and then decreased at final follow-up, leaving no statistically significant difference from the initial measurement. The difference in valgus between fractured and uninjured limb increased to a statistically significant level from post-treatment to maximum deformity and then decreased, leaving an excess from the initial measurement. CONCLUSION: In almost half the patients, late valgus deformity developed within two years post-fracture and corrected to the initial post-treatment angles. Patients should be warned of this possibility and reassured of its natural resolution. LEVEL OF EVIDENCE: IV.

Type IV capitellum fractures in children.

Capitellum fractures represent 1% of elbow fractures. A coronal shear fracture which involves the trochlea is classified as a type IV McKee fracture. The combination of its rarity in the paediatric population as well as its unique appearance on X-ray make diagnosis of this fracture a challenge. We present the case of a 14-year-old boy who sustained this fracture falling from his bike. It was diagnosed from the double arc sign on X-ray. In addition, a CT scan was obtained to aid preoperative planning. It was treated by open reduction and fixation with two headless compression screws. Follow-up at 6 months showed no avascular necrosis. The patient could achieve full extension, while flexion was reduced only by 5°. Final follow-up was conducted at 15 months. Anatomic reduction and stable internal fixation are essential for a good outcome in these uncommon paediatric fractures.

The Insertion of Electrodes in the Brain for Electrophysiological Recording or Chronic Stimulation Is Not Associated With Any Biochemically Detectable Neuronal Injury.

OBJECTIVE: The aim of this study was to evaluate the degree of brain tissue injury that could be potentially induced by the introduction of a) microrecording electrodes, b) macrostimulation electrodes, or c) chronic stimulation electrodes. We aimed to evaluate whether the use of five simultaneous microrecording tracks is associated with any brain injury not detectable by conventional imaging such as CT or MRI. MATERIALS AND METHODS: The study included 61 patients who underwent surgery for implantation of 121 DBS leads. In all cases, five simultaneous tracts were utilized for microelectrode recordings. All patients underwent measurements of serum S-100b at specific time points as follows: a) prior to the operation, and b) intraoperatively at specific stages of the procedure: 1) after opening the burr hole, 2) after the insertion of microrecording electrodes, 3) during macrostimulation, 4) at the end of the operation, and 5) on the first postoperative day. RESULTS: The levels of serum S-100B protein remained within the normal range during the entire period of investigation in all patients with the exception of two cases. In both patients, the procedure was complicated by intraparenchymal hemorrhage visible in neuro-imaging. The first patient developed a small intraparenchymal hemorrhage, visible on the postoperative MRI, with no neurological deficit. The second patient experienced a focal epileptic seizure after the insertion of the right DBS chronic lead and the postoperative CT scan revealed a right frontal lobe hemorrhage. CONCLUSION: These results strongly indicate that the insertion of either multiple recording electrodes or the implantation of chronic electrodes in DBS does not increase the risk of brain hemorrhage or of other intracranial complications, and furthermore it does not cause any biochemically detectable brain tissue damage.

Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

Dominant efficiency of nonregular patterns of subthalamic nucleus deep brain stimulation for Parkinson's disease and obsessive-compulsive disorder in a data-driven computational model.

OBJECTIVE: Almost 30 years after the start of the modern era of deep brain stimulation (DBS), the subthalamic nucleus (STN) still constitutes a standard stimulation target for advanced Parkinson's disease (PD), but the use of STN-DBS is also now supported by level I clinical evidence for treatment-refractory obsessive-compulsive disorder (OCD). Disruption of neural synchronization in the STN has been suggested as one of the possible mechanisms of action of standard and alternative patterns of STN-DBS at a local level. Meanwhile, recent experimental and computational modeling evidence has signified the efficiency of alternative patterns of stimulation; however, no indications exist for treatment-refractory OCD. Here, we comparatively simulate the desynchronizing effect of standard (regular at 130 Hz) versus temporally alternative (in terms of frequency, temporal variability and the existence of bursts or pauses) patterns of STN-DBS for PD and OCD, by means of a stochastic dynamical model and two microelectrode recording (MER) datasets. APPROACH: The stochastic model is fitted to subthalamic MERs acquired during eight surgical interventions for PD and eight surgical interventions for OCD. For each dynamical system simulated, we comparatively assess the invariant density (steady-state phase distribution) as a measure inversely related to the desynchronizing effect yielded by the applied patterns of stimulation. MAIN RESULTS: We demonstrate that high (130 Hz)-and low (80 Hz)-frequency irregular patterns of stimulation, and low-frequency periodic stimulation interrupted by bursts of pulses, yield in both pathologic conditions a significantly stronger desynchronizing effect compared with standard STN-DBS, and distinct alternative patterns of stimulation. In PD, values of the invariant density measure are proven to be optimal at the dorsolateral oscillatory region of the STN including sites with the optimal therapeutic window. SIGNIFICANCE: In addition to providing novel insights into the efficiency of low-frequency nonregular patterns of STN-DBS for advanced PD and treatment-refractory OCD, this work points to a possible correlation of a model-based outcome measure with clinical effectiveness of stimulation and may have significant implications for an energy- and therapeutically-efficient configuration of a closed-loop neuromodulation system.

Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model.

OBJECTIVE: During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinson's disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. APPROACH: The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. MAIN RESULTS: Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. SIGNIFICANCE: The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise target finalization during DBS surgery for PD.

Restoration of erect posture in idiopathic camptocormia by electrical stimulation of the globus pallidus internus.

The authors report on 2 young patients who developed drug-resistant idiopathic dystonic camptocormia (bent spine) and were treated successfully by deep brain stimulation (DBS) of the globus pallidus internus (GPi). The first patient, a 26-year-old woman, suffered for 3 years from such severe camptocormia that she became unable to walk and was confined to bed or a wheelchair. The second patient, a 21-year-old man, suffered for 6 months from less severe camptocormia; he was able to walk but only for short distances with a very bent spine, the arms in a parallel position to the legs, and the hands almost approaching the floor to potentially support him in case of a forward fall. Within a few days following DBS, both patients experienced marked clinical improvement. At most recent follow-up (44 months in one case and 42 in the other), the patients' ability to walk upright remained normal. Similar findings have only been reported recently in a few cases of camptocormia secondary to Parkinson disease or tardive dyskinesia. On the basis of the experience of these 2 idiopathic cases and the previously reported cases of secondary camptocormia with a favorable response to GPi DBS, the authors postulate that specific patterns of oscillatory activity in the GPi are vital for the maintenance of erect posture and the adoption of bipedal walking by humans.

A population level computational model of the basal ganglia that generates parkinsonian Local Field Potential activity.

Recordings from the basal ganglia's subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality-effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD.

New pure motor nerve experimental model for the comparative study between end-to-end and end-to-side neurorrhaphy in free muscle flap neurotization.

The present study demonstrates a new experimental model to compare the efficacy of end-to-end and end-to-end neurorrhaphy in free muscle flap neurotization. Forty animals were used, divided into four equal groups named A, B, C and D. The peripheral stump of the thoracodorsal nerve was stitched end-to-end in groups A and C and end-to-side in groups B and D to the long thoracic nerve. Free functional muscle transfer was simulated by putting vascular clamps to the thoracodorsal artery (FD SS8R, F: 15 to 20 g) and vein (FD SS6R, F: 10 to 15 g) for 60 minutes and transecting and then restitching the origin and insertion of the latissimus dorsi muscle. Electromyographic and histological studies were performed 150 days following completion of the experiment. The results could indicate the possibility that end-to-side neurorrhaphy might be used in free functional muscle transfer as an alternative to end-to-end neurorrhaphy. We believe that the proposed experimental model is useful for the comparative study between end-to-end and end-to-side neurorrhaphy in free muscle flap neurotization, as these are pure motor nerves and innervate synergistic muscles, are in close approximation, and have similar diameters.

Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts: an experimental study.

This study investigated the effect of local administration of nerve growth factor-7S (NGF-7S) on the axonal regrowth of mixed peripheral nerves through inside-out vein grafts. Sixty male Wistar rats were randomized into two groups (n = 30). A defect 12 mm long in the right sciatic nerve was created and repaired with an inside-out vein graft from the right jugular vein. NGF-7S (group A) or phosphate-buffered saline (group B; control) was locally administered daily during the first 3 weeks. Walking-track analysis and electrophysiological and histological-morphometric studies were carried out 4, 6, 8, 10, and 12 weeks postoperatively (subgroups a, b, c, d, and e, respectively, n = 6 each). Data analysis showed that 1) the recovery of motor function, as measured by walk pattern analysis and evoked muscle action potential, and 2) the orientation, number, myelin thickness, and diameter of myelinated fibers were better in the NGF-7S than in the control group. These findings present strong evidence of the beneficial effect of NGF-7S on peripheral nerve regeneration through inside-out vein grafts.