Recipient Reaction and Composition of Autologous Sural Nerve Tissue Grafts into the Human Brain.

Parkinson's disease (PD) is a severe neurological disease for which there is no effective treatment or cure, and therefore it remains an unmet need in medicine. We present data from four participants who received autologous transplantation of small pieces of sural nerve tissue into either the basal forebrain containing the nucleus basalis of Meynert (NBM) or the midbrain substantia nigra (SN). The grafts did not exhibit significant cell death or severe host-tissue reaction up to 55 months post-grafting and contained peripheral cells. Dopaminergic neurites showed active growth in the graft area and into the graft in the SN graft, and cholinergic neurites were abundant near the graft in the NBM. These results provide a histological basis for changes in clinical features after autologous peripheral nerve tissue grafting into the NBM or SN in PD.

The influence of posterior acromial morphology on outcomes and return to pushups in young patients undergoing arthroscopic posterior capsulolabral repair.

Background: Prior evidence has identified specific posterior acromial morphology as significantly associated with unidirectional posterior shoulder instability. The purpose of this study is to determine the influence of posterior acromial morphology on the outcomes of arthroscopic posterior capsulolabral repair (APCLR) for unidirectional posterior shoulder instability. Additionally, we sought to determine the influence of posterior acromial morphology on the rate and time to return to pushups following APCLR. Methods: We performed a retrospective review of prospectively collected data. The study included consecutive patients undergoing APCLR. Data collected included demographics, radiographic measurements including posterior acromial height (PAH) and posterior acromial tilt on preoperative scapular-Y radiographs, and patient-reported outcome measures at the preoperative and postoperative visits. In addition, starting at 6 months postoperative, patients were asked if they could perform pushups defined as at least 10 repetitions. At the final follow-up, we collected the number of pushups patients were able to perform. Results: Thirty-two consecutive patients underwent APCLR with a mean follow-up of 26 months (range, 12-41). Significant improvement from preoperative to 2 years postoperative was demonstrated in Subjective Shoulder Value (50-85), VAS (6-2.5), American Shoulder and Elbow Surgeons (48 to 83), and Western Ontario Shoulder Instability (WOSI) (1437-777), P = .001. The recurrent instability rate was 3/32 (9%). Patients with PAH > 23 (N = 17) had a recurrent instability rate of 18% (3/17) versus PAH ≤ 23 (N = 15) 0% (0/15), worse WOSI scores (P = .41), and a lower number of pushups (P = .48). The percentage of patients reporting the ability to perform pushups was (6 months/1 year/2 years) (50%/78%/95%). The mean number of pushups reported at the final follow-up was 33 (range, 1-60). Discussion: Following APCLR, approximately 50% of patients resume pushups at 6 months postoperatively, and 80% return at 1 year. Patients reported performing a mean of 33 pushups following APCLR at the final follow-up. Patients with a PAH greater than 23 on preoperative scapular-Y radiographs had a higher rate of recurrent posterior instability, worse WOSI scores, and lower return to pushups; however, the results did not meet statistical significance. Therefore, future larger studies are needed to determine if posterior acromial morphology is independently associated with worse outcomes and increased recurrent instability rates following APCLR.

A High Rate of Return to Running Is Seen After Both Arthroscopic and Open Shoulder Surgery.

Purpose: To determine the percentage of patients who report the ability to run 1 mile at various time points after arthroscopic and open shoulder surgery. Methods: We performed a retrospective review of prospectively collected data for all active-duty military patients aged 18 to 45 years who underwent shoulder surgery at a single institution over a 2-year period. The rehabilitation protocol discouraged running before 3 months, but all patients were able to return to unrestricted running at 3 months postoperatively. Patients were excluded if they lacked 1-year follow-up data. Parameters collected included demographic information and validated patient-reported outcome measures at the preoperative and short-term postoperative visits, as well as patients' ability to run at least 1 mile postoperatively. Results: A total of 126 patients were identified who underwent shoulder surgery with return-to-running data. Compared with baseline, significant improvements in patient-reported outcomes were shown at 1 and 2 years postoperatively (P = .001). The percentage of patients reporting the ability to run 1 mile postoperatively was 59% at 3 months, 74% at 4.5 months, 79% at 6 months, 83% at 12 months, and 91% at 24 months. There was no significant difference in patients undergoing shoulder surgery for instability versus non-instability diagnoses or in patients undergoing open versus arthroscopic anterior stabilization. All 11 patients unable to return to running at final follow-up had chronic lower-extremity diagnoses limiting their running ability. Conclusions: Young military athletes undergoing arthroscopic and open shoulder surgery have a high rate of early return to running. Approximately 60% of patients report the ability to run 1 mile at 3 months postoperatively, and three-quarters of patients do so at 4.5 months. Age, sex, military occupation, underlying diagnosis or type of surgery did not influence the rate of return to running after shoulder surgery. Level of Evidence: Level IV, therapeutic case series.

Visualization of the Movement Disorder Society Unified Parkinson's Disease Rating Scale Results.

We sought to design a data visualization platform to represent the Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) item scores in an easy-to-use display without modification of the raw data or summary scores. Score items for Parts I, II, and IV were arranged as separate inline blocks, while Part III item blocks were arranged in an anatomical fashion. A color scale was created to represent symptom severity and changes observed from one exam to another. We have found the visualization helpful for quickly defining the most troublesome symptoms and their anatomical location enabling communication of the results and interpretations.

Rate and time to return to shooting following arthroscopic and open shoulder surgery.

Background: There is limited information on return to shooting following shoulder surgery. The purpose of this study is to determine the rate and timing for resuming shooting a rifle following shoulder surgery. Methods: We performed a retrospective review of prospectively collected data. The study included patients undergoing arthroscopic and open shoulder stabilization for unidirectional shoulder instability, and arthroscopic surgery for rotator cuff tears, SLAP lesions, biceps tendinopathy, and acromioclavicular pathology. Data collected included the laterality of surgery, shooting dominance, and patient-reported outcome measures at the preoperative and postoperative visits. Starting at the 4.5-month clinic visit, patients were asked if they could shoot a military rifle. Results: One hundred patients were identified with arthroscopic and open shoulder surgery with a mean age of 30 years (range, 18-45) and a mean follow-up of 24 months (range, 12-32). The cohort consisted of patients undergoing arthroscopic Bankart repair (n = 23), arthroscopic posterior labral repair (n = 18), open Latarjet (n = 16), mini-open subpectoral biceps tenodesis (OBT) (n = 25), OBT with open distal clavicle resection (DCR) (n = 10), open DCR (n = 4), and arthroscopic rotator cuff repair with concomitant OBT (n = 4). Significant improvement in SSV, VAS, ASES, and WOSI was shown at 1-year postoperative, SSV 85, VAS 2, ASES 85, WOSI 239, P = .001. The percentage of patients reporting the ability to shoot a military rifle postoperatively were 47%, 63%, 85%, and 94% at 4.5 months, 6 months, 1 year, and 2 years, respectively. At 4.5 months postoperatively, patients who underwent surgery ipsilateral to their shooting dominance (n = 59) had a rate of return to shooting (33%) versus shoulder surgery on the contralateral side of shooting dominance (n = 41) (60%), P = .04. However, there was no significant difference in the groups at 6 months and 1 year. Additionally, there was a significant difference in the rate of return to shooting at 6 months in patients undergoing arthroscopic posterior labral repair versus the remainder of the cohort (posterior instability (33%) vs. (69%), P = .016), and a significant difference between posterior shoulder stabilization and anterior shoulder stabilization (70%), P = .03. Conclusion: Patients undergoing arthroscopic and open shoulder surgery have a high rate of return to shooting. Approximately 60% of patients resume shooting at 6 months postoperatively and 85% return at 1 year. Patients undergoing shoulder surgery on the contralateral side of their shooting dominance return to shooting significantly faster than those with shoulder surgery ipsilateral to their shooting dominance. Additionally, those undergoing arthroscopic posterior shoulder stabilization return to shooting at a slower rate than anterior stabilization surgery.

Direct delivery of an investigational cell therapy in patients with Parkinson's disease: an interim analysis of feasibility and safety of an open-label study using DBS-Plus clinical trial design.

Objective: To evaluate the interim feasibility, safety and clinical measures data of direct delivery of regenerating peripheral nerve tissue (PNT) to the substantia nigra (SN) in participants with Parkinson's disease (PD). Methods: Eighteen (13 men/5 women) participants were unilaterally implanted with PNT to the SN, contralateral to the most affected side during the same surgery they were receiving deep brain stimulation (DBS) surgery. Autologous PNT was collected from the sural nerve. Participants were followed for safety and clinical outcomes for 2 years (including off-state Unified Parkinson's Disease Rating Scale (UPDRS) Part III assessments) with study visits every 6 months. Results: All 18 participants scheduled to receive PNT implantation received targeted delivery to the SN in addition to their DBS. All subjects were discharged the following day except for two: post-op day 2; post-op day 3. The most common study-related adverse events were hypoaesthesia and hyperaesthesias to the lateral aspect of the foot and ankle of the biopsied nerve (6 of 18 participants experienced). Clinical measures did not identify any hastening of PD measures providing evidence of safety and tolerability. Off-state UPDRS Part III mean difference scores were reduced at 12 months compared with baseline (difference=-8.1, 95% CI -2.4 to -13.9 points, p=0.005). No complications involving dyskinesias were observed. Conclusions: Targeting the SN for direct delivery of PNT was feasible with no serious adverse events related to the study intervention. Interim clinical outcomes show promising results meriting continued examination of this investigational approach. Trial registration number: NCT02369003.

High Incidence of Anterior Shoulder Pain in Young Athletes Undergoing Arthroscopic Posterior Labral Repair for Posterior Shoulder Instability.

PURPOSE: The purposes of this study were to determine the incidence of anterior shoulder pain in young athletes undergoing arthroscopic posterior labral repair for symptomatic unidirectional posterior shoulder instability and in patients with preoperative anterior shoulder pain treated without biceps tenodesis at the time of arthroscopic posterior labral repair who underwent a revision biceps tenodesis procedure at short-term follow up. METHODS: A retrospective review was performed at a single institution over a 24-month period. The study included young patients who underwent an arthroscopic posterior labral repair for symptomatic unidirectional posterior shoulder instability. The electronic medical record, magnetic resonance arthrograms, and arthroscopic images were reviewed to exclude patients with posterior labral tears with anterior labral tear or SLAP (superior labrum anterior-to-posterior) tear extension on advanced imaging and arthroscopic examination. Data collected included the presence of preoperative tenderness to palpation of the biceps tendon in the groove, the results of a preoperative Speed test, postoperative Subjective Shoulder Value, the presence of postoperative anterior shoulder pain, and the need for a secondary biceps tenodesis. RESULTS: We identified 65 patients who underwent arthroscopic labral repair for posterior shoulder instability. From this cohort, 26 patients with symptomatic unidirectional posterior shoulder instability underwent an arthroscopic posterior labral repair. The incidence of preoperative anterior shoulder pain with Zone 2 biceps groove tenderness and a positive Speed test was identified in 20 of 26 patients (76.9%). Of 26 patients, 5 (19%) had concomitant biceps tenodesis. The median postoperative Subjective Shoulder Value was 80 (interquartile range, 60-90) at median follow-up of 2.1 years. Of the 20 patients with preoperative anterior shoulder pain, 8 of 20 (40%) reported persistent anterior pain. One patient (4.7%) underwent a secondary biceps tenodesis. CONCLUSIONS: There is a high incidence of anterior shoulder pain and Zone 2 biceps groove tenderness in patients undergoing isolated arthroscopic posterior labral repair for unidirectional posterior shoulder instability. At short-term follow-up, few patients required a secondary biceps tenodesis procedure; however, 30% of patients had persistent anterior shoulder pain. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic case series.

Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson's Disease.

BACKGROUND: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. OBJECTIVES: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson's disease. METHODS: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. RESULTS: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. CONCLUSIONS: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results.

Ultrasound-Guided Biceps Tendon Sheath Injections Frequently Extravasate Into the Glenohumeral Joint.

PURPOSE: To evaluate the frequency of glenohumeral joint extravasation of ultrasound (US)-guided biceps tendon sheath injections. METHODS: Fifty shoulders with a clinical diagnosis of bicipital tenosynovitis pain received a US-guided biceps sheath injection with anesthetic, steroid, and contrast (5.0 mL mixture) followed immediately by orthogonal radiographs to localize the anatomic distribution of the injection. Radiographic evaluation of contrast localization was determined and interobserver reliability calculated. RESULTS: All 50 postinjection radiographs (100%) demonstrated contrast within the biceps tendon sheath. In addition, 30 of 50 (60%) radiographs also revealed contrast in the glenohumeral joint. Interobserver reliability for determination of intraarticular contrast was good (kappa value 0.87). CONCLUSIONS: US-guided bicipital sheath injections reproducibly result in intrasheath placement of injection fluid. Bicipital sheath injections performed with 5 mL of volume result in partial extravasation into the joint 60% of the time. These data may be useful for surgeons who use the results of diagnostic biceps injections for diagnosis and surgical decision-making. LEVEL OF EVIDENCE: III, prospective cohort study, diagnosis.

Pregnancy outcomes in women with onset of type 1 diabetes mellitus less than 18 years of age.

BACKGROUND: Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with an increased risk of congenital malformations, obstetric complications and neonatal morbidity. This study aims to investigate maternal, perinatal and neonatal outcomes of pregnancies in women with onset of T1DM less than 18 years of age. METHODS: This retrospective cohort study extracted data regarding prenatal, intrapartum and postnatal outcomes of pregnancies in women with onset of T1DM<18 years identified from the diabetes in pregnancy register at University Maternity Hospital Limerick, treated from July 1, 2007 to July 1, 2017. RESULTS: Seventeen women with onset of T1DM <18 years gave birth to 23 live infants during the period studied. 73.9% of pregnancies were unplanned. Only 21.7% of pregnancies took preconceptual folic acid. 60.9% of infants required treatment for hypoglycemia. CONCLUSION: The high prevalence of unplanned pregnancy and poor uptake of prepregnancy care must be improved on in order to improve outcomes for this high-risk group.

Modulation of epileptogenesis: A paradigm for the integration of enzyme-based microelectrode arrays and optogenetics.

BACKGROUND: Genesis of acquired epilepsy includes transformations spanning genetic-to- network-level modifications, disrupting the regional excitatory/inhibitory balance. Methodology concurrently tracking changes at multiple levels is lacking. Here, viral vectors are used to differentially express two opsin proteins in neuronal populations within dentate gyrus (DG) of hippocampus. When activated, these opsins induced excitatory or inhibitory neural output that differentially affected neural networks and epileptogenesis. In vivo measures included behavioral observation coupled to real-time measures of regional glutamate flux using ceramic-based amperometric microelectrode arrays (MEAs). RESULTS: Using MEA technology, phasic increases of extracellular glutamate were recorded immediately upon application of blue light/488 nm to DG of rats previously transfected with an AAV 2/5 vector containing an (excitatory) channelrhodopsin-2 transcript. Rats receiving twice-daily 30-sec light stimulation to DG ipsilateral to viral transfection progressed through Racine seizure stages. AAV 2/5 (inhibitory) halorhodopsin-transfected rats receiving concomitant amygdalar kindling and DG light stimuli were kindled significantly more slowly than non-stimulated controls. In in vitro slice preparations, both excitatory and inhibitory responses were independently evoked in dentate granule cells during appropriate light stimulation. Latency to response and sensitivity of responses suggest a degree of neuron subtype-selective functional expression of the transcripts. CONCLUSIONS: This study demonstrates the potential for coupling MEA technology and optogenetics for real-time neurotransmitter release measures and modification of seizure susceptibility in animal models of epileptogenesis. This microelectrode/optogenetic technology could prove useful for characterization of network and system level dysfunction in diseases involving imbalanced excitatory/inhibitory control of neuron populations and guide development of future treatment strategies.

Investigating the role of early low-dose aspirin in diabetes: A phase III multicentre double-blinded placebo-controlled randomised trial of aspirin therapy initiated in the first trimester of diabetes pregnancy.

BACKGROUND: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. METHODS: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). DISCUSSION: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks' gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation.

Drug treatment strategies for depression in Parkinson disease.

INTRODUCTION: Depression is a common non-motor symptom in Parkinson disease (PD), occurring in approximately 20% of patients with PD. While depression can occur anytime in the disease process, it predates PD diagnosis in about 30% of patients. Between 20% and 60% of depressed patients with PD are either without recognition or treatment of their depression. AREAS COVERED: The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon. EXPERT OPINION: Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future.

Martial arts technique for control of severe external bleeding.

OBJECTIVES: Haemorrhage control is a critical component of preventing traumatic death. Other than the battlefield, haemostatic devices, such as tourniquets or bandages, may not be available, allowing for significant avoidable blood loss. We hypothesised that compression of vascular pressure points using a position adapted from the martial art of Brazilian Jiu-Jitsu could be adapted to decrease blood flow velocity in major extremity arteries. METHODS: Knee mount compression was applied to the shoulder, groin and abdomen of healthy adult volunteer research subjects from Seattle, Washington, USA, from March through May 2018. Mean arterial blood flow velocity (MAV) was measured using ultrasound in the brachial and femoral arteries before and after compression. A MAV decrease greater than 20% with compression was deemed clinically relevant. RESULTS: For 11 subjects, median (IQR) MAV combining all anatomical locations tested was 29.2 (34.1, 24.1) cm/s at baseline and decreased to 3.3 (0, 19.1) cm/s during compression (Wilcoxon p<0.001). MAV was significantly decreased during compression for each individual anatomical position tested (Wilcoxon p≤0.004). Per cent (95% CI) MAV reduction was significantly greater than 20% for shoulder compression at 97.5%(94% to 100%) and groin compression at 78%(56% to 100%), but was not statistically greater for abdominal compression at 35%(12% to 57%). Complete vessel occlusion was most common with compression at the shoulder (73%), followed by groin (55%) and abdomen (9%) (χ² LR, p=0.018). CONCLUSION: The Brazilian Jiu-Jitsu knee mount position can significantly decrease blood flow in major arteries of the extremities. This technique may be useful for bleeding control after injury.

The Effect of Telerehabilitation on Missed Appointment Rates.

The purpose of this study was to examine the effect of telerehabilitation on missed appointment rates in a rehabilitation clinic. Clients fail to attend scheduled appointments for a variety of reasons. Unmet appointments represent a loss of financial support as well as diminished efficiency and capacity to provide services. Speech therapy utilizing multiple appointments is most difficult to maintain during a treatment regimen. This may cause individuals to miss appointments and therefore not achieve desired results. For this study, researchers utilized an intense speech therapy technique, the Lee Silverman Voice Treatment (LSVT®) to measure compliance with scheduled appointments. Participants were randomized to either in-person treatment or telerehabilitation treatment at a site distant from the speech-language pathologist. Participants in the telerehabilitation (TR) condition completed significantly more appointments than participants in the in-person (IP) condition. When comparing results of treatment for each condition, there were no significant differences in outcome whether treated in the IP or TR condition of the study for monologue and picture description tasks, which are closely associated with conversational speech. There was a difference in the reading task with participants demonstrating significantly better post treatment results in the IP condition. The reason for this disparity is unclear and warrants further study.

Reversible manifestations of extraparenchymal neurocysticercosis.

Movement disorders are uncommon manifestations of neurocysticercosis. When present, most are secondary to parenchymal lesions in the basal ganglia. Rarely, movement disorders can occur in racemose/extraparenchymal neurocysticercosis, an aggressive variant frequently associated with cerebrospinal fluid outflow obstruction and hydrocephalus. Appropriate treatment can reverse neurological manifestations.