Incidence and predictors of postural abnormalities in Parkinson's disease: a PPMI cohort study.

BACKGROUND: Axial postural abnormalities (PA) are invalidating symptoms of Parkinson's disease (PD). Risk factors for PA are unknown. OBJECTIVES: We sought to evaluate PA incidence and risk factors over the first 4-6 years of PD. METHODS: We included 441 PD patients from the Parkinson's Progression Markers Initiative (PPMI) cohort with data at diagnosis and after 4-year follow-up. PA was defined according to a posture item ≥ 2 at the Movement Disorder Society-sponsored-revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in Off therapeutic condition. The Kruskal-Wallis test was used to compare characteristics of patients without PA ('no-PA'), with PA at disease onset ('baseline-PA'), and PA developed during follow-up ('develop-PA'). To identify predictors of PA development, univariate and multivariate Cox regression analyses were performed considering demographic, clinical and therapeutic variables. RESULTS: 10.9% of patients showed PA at baseline and 23.7% developed PA within the first 4-6 years since diagnosis. Older age, malignant phenotype, higher MDS-UPDRS part III, Hoehn & Yahr, and dysautonomia (SCOPA-AUT) score, and lower levels of physical activity were predictors of PA development at the univariate analysis. Older age (Hazard ratio [HR] per year: 1.041) and higher MDS-UPDRS part III score (HR per point: 1.035) survived as PA development predictors in the multivariate analysis. CONCLUSIONS: PPMI cohort data show that > 30% of PD patients present PA within the first 4-6 years of disease. Older age at onset and higher motor burden are associated with a higher risk for PA development. The protective role of physical activity merits to be further investigated.

Different neuropsychological and brain volumetric profiles in a pair of identical twins with myotonic dystrophy type 1 indicate a non-genetic modulation of clinical phenotype.

We report on genetic and environmental modulation of social cognition abilities and brain volume correlates in two monozygotic twins (Twin1 and Twin2) with genetically confirmed myotonic dystrophy-type1 who grew up in different environmental settings. They both underwent neuropsychological assessment (i.e., Intelligent Quotient [IQ], theory of mind, emotion recognition tests), and MRI scanning to evaluate regional brain volumetrics compared to 10 gender and sex-matched healthy controls. Against a normal IQ level in both patients, Twin1 was more impaired in emotional processing and Twin2 in cognitive aspects of social cognition. Both patients showed grey matter (GM) atrophy in Brodmann Areas 23/31 (BA23/31) and BA7 bilaterally, while Twin2 showed additional GM loss in right BA46. Both patients showed a similar pattern of white matter atrophy involving the thalamus, basal ganglia, and uncinate fasciculus. White matter atrophy appeared to be mostly driven by genetics, while grey matter volumes appeared associated with different impairments in social cognition and possibly modulated by environment.

Celocentesis for Early Prenatal Diagnosis in Couples at-Risk for ß-Thalassemia and Sicilian (δß)0-Thalassemia.

The procedures commonly used for prenatal diagnosis (PND) of thalassemia are villocentesis or amniocentesis, respectively, at the 11th and 16th weeks of gestation. Their main limitation is essentially due to the late gestation week in which diagnosis is performed. The celomic cavity is accessible between the 7th and 9th weeks of gestation and it has been demonstrated that it contains embryonic erythroid precursor cells as a source of fetal DNA for earlier invasive PND of thalassemia and other monogenic diseases. In this study, we report the use of celomatic fluids obtained from nine women with high-risk pregnancies for Sicilian (δß)0-thalassemia [(δß)0-thal] deletion (NG_000007.3: g.64336_77738del13403) and ß-thalassemia (ß-thal). Fetal cells were isolated by a micromanipulator, and nested polymerase chain reaction (PCR) and short tandem repeats (STRs) analysis were performed. Prenatal diagnosis was successfully performed in all examined cases. One fetus was a compound heterozygote for (δß)0- and ß-thal, three fetuses were found to be carriers of ß-thal, four fetuses carriers of a Sicilian 뫧 deletion, and one fetus without parental mutations. Accidentally, a rare case of paternal triploidy was observed. The genotypic analysis, carried out both by amniocentesis and on abortive tissue or after birth, showed concordance with results obtained on fetal celomic DNA. Our results unequivocally show that fetal DNA can be obtained by nucleated fetal cells present in the celomatic fluid and demonstrate, for the first time, that PND of Sicilian (δß)0-thal and ß-thal is feasible at an earlier time in pregnancy than other procedures.

Far Infrared Radiation Therapy for Gynecological Cancer-Related Lymphedema Is an Effective and Oncologically Safe Treatment: A Randomized-Controlled Trial.

Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference (p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.

Role of the Cadaver Lab in Lymphatic Microsurgery Education: Validation of a New Training Model.

BACKGROUND: Microsurgical transplantation of vascularized lymph nodes (VLNT) or lymphatic vessels (VLVT) alongside derivative lymphaticovenous procedures are promising approaches for treatment of lymphedema. However, clinically relevant training models for mastering these techniques are still lacking. Here we describe a new training model in human cadaver and validate its use as training tool for microsurgical lymphatic reconstruction. METHODS: 10 surgeons with previous exposure to microsurgery were trained in a controlled environment. Lymphatic vessel mapping and dissection in 4 relevant body regions, harvesting of five different VLNTs and one VLVT were performed in 5 fresh-frozen cadavers. The number of lymphatic vessels and lymph nodes for each VLNT were recorded. Finally, the efficacy of this model as training tool was validated using the Dundee Ready Education Environment Measure (DREEM). RESULTS: The average cumulative DREEM score over each category was 30,75 (max = 40) while individual scoring for each relevant category revealed highly positive ratings from the perspective of teaching (39,3), training 40,5 (max = 48) and self perception of the training 30,5 (max = 32) from all participants. The groin revealed the highest number of lymphatic vessels (3.2 ± 0.29) as all other regions on the upper extremity, while the gastroepiploic VLNT had the highest number of lymph nodes (4.2 ± 0.37). CONCLUSIONS: This human cadaver model represents a new, reproducible "all-in-one" tool for effective training in lymphatic microsurgery. Its unique diligence in accurately reproducing human lymphatic anatomy, should make this model worth considering for each microsurgeon willing to approach lymphatic reconstruction.

Bipedicled distally based medial plantar artery perforator flap for forefoot reconstruction: A case report.

Reconstruction of soft-tissue defects in the foot weight-bearing area should encompass sensate and robust skin. Regarding forefoot defects, distally based medial plantar artery (MPA) flap is an ideal option. However, considering variation of the terminal branches of the MPA, reverse flow flaps can be unreliable with an increasing risk of venous congestion or insufficient arterial flow. In this report, we present a case of the use of reverse flow MPA flaps with dual flow vascularization. The patient was a 37-year-old female who presented a 7 × 3 cm soft-tissue defect of the right forefoot after wide local excision following melanoma. Reconstruction happened with a perforator distally based bipedicled flap (8 × 4 cm) on the MPA though keeping an enhanced vascularization through both superficial (sMPA) and deep (dMPA) medial plantar arteries. Donor site was closed with skin graft. Patient was discharged from hospital at postoperative Day 10 and healed uneventfully with progressive start walk was possible again. A full weight bearing with normal shoes was possible after 8 weeks. Good healing and no functional impairment were present after 9 months of follow-up. We believe this dual vascularization concept may be adopted when possible to improve the overall circulation of the flap and to prevent risks of vascular insufficiency or vein congestion.

Lymphatic Leaks of the Thigh and Inguinal Region: Combined Plastic Surgery Approaches for an Effective Treatment Algorithm.

BACKGROUND: Surgical procedures interfering with the draining nodes in the inguinal region carry the intrinsic risk of lymphatic complications. Lesions of the inguinal lymphatic network can lead to lymphocele or lymphocutaneous fistulas and can eventually be associated to limb lymphedema with consequent high morbidity. OBJECTIVES: This article describes a new surgical algorithm based on wound properties to properly address lymphatic complications of the inguinal area. Based on our experience, surgical solutions ranged from selective lymphatic vessel ligation to microsurgical lymphatic fistula treatment and free tissue transfer. METHODS: Fourteen consecutive patients underwent surgery in our department following failed attempts to address persistent lymphatic leaks. Patient characteristics such as smoking, previous surgeries, comorbidities, and wound properties were considered. Identification of the leak was performed using blue patent dye and indocyanine green fluorescence. Surgical reconstruction occurred, according to our algorithm. RESULTS: Lymphatic leaks were visualized in 11 of 14 patients. Direct closure of the wound after leak ligation could be performed in 4 of 14 patients. Multilymphatic into vein anastomosis was performed in 3 of 14 patients, and the remaining patients benefited from flap surgery based on the wound defects. All 14 patients had successful outcomes (100%) with early drain removal (average, 6 [SD, 6] days) and definitive wound healing 2 weeks postoperatively. After a mean follow-up of 12 (SD, 2.9) months, no clinical infection, lymphatic complication, or wound breakdown occurred. One patient had a partial recurrence that did not require surgical intervention. CONCLUSIONS: A stepwise approach, combining lymphatic surgery principles and plastic surgery flap techniques, can lead to an effective treatment algorithm where surgical options are wound tailored to guarantee the best functional outcomes.

Comparisons of fascio-cutaneous anterolateral thigh and sandwich fascial ALT free flap in the distal extremity reconstruction.

INTRODUCTION: The anterolateral thigh (ALT) flap is considered a workhorse reconstructive option; however, it is encumbered by its bulkiness that can result in poor final outcome and need for revision surgery. The aim of the present study was to compare the standard cutaneous ALT free flap and sandwich fascial ALT (SALT) free flap, raised harvesting between the Scarpa's fascia and the crural fascia, for distal extremity soft tissue reconstruction, including pre- intra- and post-operative considerations and outcomes. PATIENTS AND METHODS: A retrospective review of medical records from 2013 to 2018 of 24 patients who underwent distal extremity reconstruction with standard fascio-cutaneous ALT flap (13 patients) and SALT flap (11 patients) was performed. The mean defect dimensions were 12 × 6.5 cm in group 1 and 12 × 6 in group 2. Surgical outcomes and quality of life were assessed (through the upper extremity functional scale and the lower extremity functional scale questionnaires. RESULTS: The mean flap dimensions were 13.1 × 7.1 in group 1 and 14.1 × 7.8 in group 2, the overall flap success rate was 100% (one microvascular venous thrombosis occurred in group 1), no statistically significant difference was recorded regarding microvascular thrombosis (one patient in group p = .369) and infections (one patient in group 1, p = .36) while a statistically significant difference was presence regarding the number of secondary/debulking procedures (6 patients vs. 0) (p = .0076) and the quality of life perception showed an overall better perception in group 2 with statistical significant difference (p = .03). CONCLUSION: The SALT flap represents a valid option, as showed through our preliminary data, when a thin and robust reconstruction is required when dealing with distal extremities soft tissue reconstruction.

Free Versus Pedicled Anterolateral Thigh Flap for Abdominal Wall Reconstruction.

BACKGROUND/AIM: Large full thickness abdominal wall defects following malignancies can be a reconstructive challenge. The purpose of this study was to analyze long-term outcomes and complications following abdominal wall reconstruction using composite antero-lateral thigh (ALT) flaps. PATIENTS AND METHODS: The study retrospectively investigated 16 consecutive patients who underwent abdominal wall reconstruction with autologous flap between May 2003 and March 2018. Volumetric flap analysis was used to assess flap atrophy over time, evaluating the role of denervation and reinnervation. The long-term outcome was assessed to compare the two groups (free vs. pedicled ALT flap reconstructions). RESULTS: All flaps successfully covered the defects. We found a significant increase in flap resorption in free flaps when compared to pedicled ones. Abdominal bulging was seen in 3 out of 16 (19%) patients after more than 12 months follow-up, in close correlation with mesh absence. CONCLUSION: Free flaps were shown to be equally effective as their pedicled counterparts, without significant increase in complication rate.

A Systematic Review of Outcomes After Genital Lymphedema Surgery: Microsurgical Reconstruction Versus Excisional Procedures.

INTRODUCTION: Genital lymphedema (GL) surgery can be either palliative or functional. Palliative procedures involve excision of the affected tissue and reconstruction by either local flaps or skin grafts. Reconstructive procedures aim to restore lymphatic flow through microsurgical lymphaticovenous anastomoses (LVAs). This systematic analysis of outcomes and complication rates aims to compare outcomes between these surgical treatment options for GL. METHODS: A systematic review of the PubMed database was performed with the following search algorithm: (lymphorrhea or lymphedema) and (genital or scrotal or vulvar) and (microsurgery or "surgical treatment"), evaluating outcomes, and complications after surgical treatment of GL. RESULTS: Twenty studies published between 1980 and 2016 met the inclusion criteria (total, 151 patients). Three main surgical treatments for GL were identified. Surgical resection and primary closure or skin graft was the most common procedure (46.4%) with a total complication rate of 10%. Surgical resection and flap reconstruction accounted for 39.1% of the procedures with an overall complication rate of 54.2%. Lympho venous shunt (LVA) procedures (14.5%) had a total complication rate of 9%. CONCLUSIONS: This review demonstrates a lack of consensus in both the preoperative assessment and surgical management of GL. Patients receiving excisional procedures tended to be later stage lymphedema. Patients in the excision and flap reconstruction group seemed to have the highest complication rates. Microsurgical LVAs may represent an alternative approach to GL, either alone or in combination with traditional procedures.

Rationale for Study of the Deep Subfascial Lymphatic Vessels During Lymphoscintigraphy for the Diagnosis of Peripheral Lymphedema.

PURPOSE: The current study aimed to determine the utility of including the study of deep subfascial lymphatic vessels in a 2-compartment lymphoscintigraphy for the diagnosis of lymphedema in patients with limb swelling. Lymphoscintigraphy is a valuable imaging tool for the timely diagnosis of peripheral lymphedema. However, there is a lack of standardization in its application, especially regarding which type of lymphatic vessels to examine (superficial, deep, or both). METHODS: Two hundred fifty-eight patients with lymphedema underwent segmental lymphoscintigraphy. The transport index (TI) was calculated to categorize the flow of the superficial and deep vessels as normal (<10) or pathological (≥10). The scores from 248 patients (48 unilateral arm, 86 unilateral leg, 114 bilateral leg) were tested with a 3-way analysis of variance to examine the relationship between affected limb, deep or superficial pathways, and primary or secondary lymphedema. The relationship between clinical presentation and TI was also investigated. RESULTS: In general, primary and secondary lymphedema patients had similar patterns of lymphoscintigraphic lymphatic abnormalities. Patients with unilateral clinical presentation can have bilateral TI abnormalities. The vast majority of patients (88%-98%) had either the deep subfascial vessels alone, or both the superficial and deep vessels, with a pathological TI. CONCLUSIONS: A 2-compartment lymphoscintigraphy is able to accurately detect lymphatic flow abnormalities in patients with limb swelling. Given that the vast majority of patients had deep lymphatic vessels abnormalities, inclusion of these vessels in the lymphoscintigraphic diagnostic protocol is recommended.

Split-sciatic nerve surgery: A new microsurgical model in experimental nerve repair.

INTRODUCTION: Sciatic experimental surgery in rat often leads to hindlimb autophagy, with considerable ethical and research issues. In this work, the distal part of the sciatic nerve was split following the natural bifurcation between tibial and peroneal branches, before applying regenerative stem cells in a fibrin conduit on the peroneal segment. The new microsurgical model was tested in terms of animal morbidity and consistency of research outcomes, particularly comparing to the standard total sciatic axotomy procedure. MATERIALS AND METHODS: After dissection of sciatic the nerve, the tibial and peroneal fibres were split upwards and a total axotomy was performed in the peroneal side. The 1 cm nerve gap between the proximal sciatic nerve and peroneal nerve was crossed using fibrin conduits. The tibial nerve was not included. Experimental groups involved either empty or fibrin conduit seeded with Schwann cell-like differentiated adipose derived stem cells (dASC) (Fib + dASC). Autografts and sham rats were used as controls (total n = 20). At 12 weeks post-implantation, an extensive histomorphometric analysis was performed. Functional aspects of regeneration were analysed by walking track analysis. RESULTS: No major autophagy occurred using the split-sciatic technique. A detailed histomorphometric analysis showed consistent results with previous literature using fibrin conduits in a full sciatic axotomy experimental setting. Walking track analysis reflected the histological regeneration pattern, displaying superior regeneration in both autograft and dASC groups. CONCLUSION: Split-Sciatic nerve surgery reduced animal morbidity, while being representative of the whole nerve as regeneration outcomes were consistent with previous data obtained on the whole sciatic nerve. The decreased autophagy rate allowed for a more efficient functional evaluation.

Mastering Lymphatic Microsurgery: A New Training Model in Living Tissue.

BACKGROUND: Advanced microsurgical techniques have emerged as a promising approach for the treatment of lymphedema, but achieving international standards is limited by a scarcity of adequate training models. The purpose of this report is to describe our in vivo porcine training model for microsurgery. STUDY DESIGN: Five female common-breed pigs (Sus scrofa domesticus) weighing 20 to 28 kg were placed under general anesthesia, and blue patent violet dye was injected to highlight lymphatic structures and prepare the pigs for anatomical exploration and microsurgery. The number and type of patent anastomoses achieved and lymph node flaps created and any anatomical differences between porcine and human vessels were noted, in light of evaluating the use of pigs as a training model for microsurgery in living tissue. RESULTS: Multiple lymphatic-venous anastomoses were created at the site of a single incision made at the subinguinal region, running medial and parallel to the saphenous vessels. Ten multiple lymphatic-venous anastomoses were created in total, and all were demonstrated to be patent. Four lymph node flaps were prepared for lymph node transfer. The superficial lymphatic collector system in the caudal limb of the pig was identified and described with particular reference to the superficial, medial (dominant), and lateral branches along the saphenous vein and its accessory. CONCLUSIONS: The authors present a safe and adaptable in vivo experimental microsurgical porcine model that provides the opportunity to practice several advanced lymphatic microsurgical techniques in the same animal. The ideal lymph node transfer training model can be developed from this anatomical detail, giving the opportunity to use it for artery-to-artery anastomoses, vein-to-vein anastomoses, and lymphatic-to-lymphatic anastomoses.

Fibro-Lipo-Lymph-Aspiration With a Lymph Vessel Sparing Procedure to Treat Advanced Lymphedema After Multiple Lymphatic-Venous Anastomoses: The Complete Treatment Protocol.

BACKGROUND: In lymphedema, excess adipose tissue occurs with progression of the disease because of chronic lymph stasis, impeding lymphatic flow. Recently, liposuction has been used as a less-invasive procedure to remove this excess tissue. Given the existing poor lymph drainage in patients with lymphatic diseases, extra caution should be taken to avoid damaging lymphatic vessels during liposuction. We developed a new technique (Fibro-Lipo-Lymph-Aspiration with a Lymph Vessel Sparing Procedure [FLLA-LVSP]) to improve chronic swelling in patients with advanced lymphedema. The FLLA-LSVP highlights the superficial lymphatic pathways in the treated limb. This visibility allows surgeons to avoid these pathways, while removing the maximum amount of excess tissue. METHOD: One hundred forty-six patients with primary or secondary lymphedema that had already been treated by lymphatic microsurgery, in Genoa, Italy, were included in this retrospective study. All patients had residual fibrotic/adipose tissue, resistant to conservative treatments. Indocyanine green fluorescent dye and Blue Patent Violet dye were injected laterally/medially to the main superficial veins at the wrist/ankle of the limb to be treated. Using a photodynamic camera, the superficial lymphatic network was made visible and sketched onto the skin in indelible ink. After the microlymphography, the excess adipose tissue was carefully aspirated. Preoperative and postoperative excess limb volume was calculated using circumferential measurements and the formula of a frustum. RESULTS: For the upper limb, 0.80 L, on average, and 2.42 L for the lower limb were removed with the FLLA-LVSP. For the upper limb, there was an average presurgery excess volume of 20.19%, which reduced to 2.68% after the FLLA-LVSP (Z score = -6.90, P < 0.001). Similarly, for the lower limb, there was an average presurgery excess limb volume of 21.24% and a reduction to 2.64% postoperatively (Z score = -3.57, P < 0.01). Immediate postoperative microlymphography and Blue Patent Violet test confirmed no lymphatic complications. No episodes of postoperative infection occurred. CONCLUSIONS: The FLLA-LVSP is efficient. An entire leg can be completed within 90 minutes. Recovery time is short, and cosmetic results are immediate. More importantly, the removal of excess tissue is completed without further damage to lymphatic vessels. When used after microsurgery, FLLA-LVSP offers the possibility of removing almost all obstacles to lymphatic flow.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

BACKGROUND: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. METHODS: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. RESULTS: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. CONCLUSIONS: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

A mild phenotype associated with a de novo microdeletion 10q23.1-q23.2: a new patient with a novel feature.

Chromosome 10q23 contains several genes, includingPTENandBMPR1A, the mutations or microdeletion of which are associated with aggressive polyposis and malignancies in children. Deletions in this chromosomal region have also been associated with heart anomalies, developmental delay and macrocephaly. Most of the cases reported involve thePTENandBMPR1Agenes, usually associated with complex and severe anomalies. We report a case of a boy with a de novo interstitial microdeletion in 10q23.1-q23.2 spanning 6.7 Mb with boundaries from 82 087 077 to 88 847 906, not includingPTENandBMPR1A Clinical features consisted of mildly dysmorphic facies, frontal telangiectasias, poor scholastic performance and hyperactivity. Furthermore, the boy presented toe anomalies, which appeared to be novel features associated with 10q23 deletion. Further observations of 10q23.1-q23.2 deletions are necessary to confirm the clinical features observed in the proband, and to show that deletion or mutations not involvingPTENandBMPR1Amay not be associated with severe neurological impairment and malformation anomalies.