Nerve repair and regeneration: Biological tubulization limits and future perspectives.

Peripheral nerve physiology and regeneration has been observed and investigated in literature but surgical applications to reconstruct and restore motor or sensory functions are still in a developmental phase. The peripheral nerve progresses slowly and incompletely compared with other tissues, it may provoke separations of the nerve stumps and the axonal proliferation of the conduits is restricted to 30 mm. Recent surgical attempts to treat proximal nerve injures include direct nerve restoration, transfer, and autografting measures with favorable results. Moreover, studies are suggesting that engineering tissue tubes maybe as effective as nerve grafting to restore separations of more than 4 cm toward optimal nerve repair.

Predictive and protective factors for partial necrosis in DIEP flap breast reconstruction: does nulliparity bias flap viability?

Although success rate of deep inferior epigastric perforator (DIEP) flap breast reconstruction has greatly improved, complications still occasionally occur. Perfusion-related complications (PRCs) (ie, fat necrosis and partial flap necrosis) are the most frequent concern, affecting aesthetic final result of the reconstructed breast. The aim of our study was to retrospectively investigate 287 consecutive DIEP flap breast reconstructions to investigate predictive and protective factors for PRCs.From May 2004 to February 2012, 287 DIEP flap breast reconstructions were performed on 270 patients; 247 unilateral flaps, including Holm vascular zones I to III, were retrospectively selected and analyzed. Tobacco use, mean blood pressure over the first postoperative 48 hours, superficial epigastric vein drainage, medial/lateral row perforator, nulliparity, crystalloid versus combined crystalloid/colloid intravenous fluid infusion therapy, and learning curve were evaluated by univariate and multivariate logistic regression analyses.Perfusion-related complications occurred 32 (12.9%) times, 79 (31.9%) patients were smokers, 48 (19.4%) showed postoperative mean blood pressure less than 75 mm Hg, 29 (11.7%) were nulliparous, and 173 (70%) had superficial epigastric vein drainage. Selected perforators were 110 (44.5%) from lateral row, 137 (55.5%) from medial row; 91 (36.8%) received crystalloid fluid infusion, whereas 156 (63.2%) combined crystalloid/colloid fluid infusion. From univariate analysis emerged significance of nulliparity, perforator row and intravenous fluid infusion for PRC. Nevertheless, multivariate model confirmed only nulliparity as a significant risk factor (P = 0.029), although variable correlations to other predictors were found: both medial row perforator and combined crystalloid/colloid fluid infusion potentially decrease the PRC risk of 11.6% and 27.6%, respectively. Learning curve did not show significant decrease of PRC risk over time.Our study first proved nulliparity as a statistically significant predictor for PRCs in DIEP flap breast reconstruction, possibly due to different superficial abdominal perfusion between pluriparous and nulliparous women, with potential weaker pattern of perforators and smaller angiosomes in the latter. The choice of medial row perforators and combined crystalloid/colloid fluid infusion might reduce PRC risk.

Flexor Tendon Continuity and Negative X-ray: The "Combo" Negative Features in Finger Subamputation.

Background: The subamputation of fingers with vascular compromise presents a surgical challenge. Although tissue continuity may be considered a favourable prognostic element, in our experience, we noticed that there is not always a direct correlation between soft tissue involvement, radiographic appearance and final outcome. Methods: We included, in our study, all cases of vascular pedicle injury in which finger salvage was attempted with microsurgical revascularisation. Exclusion criteria were: integrity of both vascular pedicles, pedicle lesion without global circulatory compromise and patients treated immediately with amputation. Results: Between May 2018 and July 2023, 27 male patients with finger subamputation injuries were treated at our institution. In 11 cases of injured fingers, the only intact tissue was the flexor digitorum profundus (FDP) or flexor pollicis longus (FPL). Our global failure rate was 49%; whereas, in the subgroup of the 11 cases with continuity of the FDP or FPL, the failure rate rose to 73% and when the fingers showed flexor tendon integrity and radiographs demonstrated minimal bone damage, revascularisation failure was observed in all cases (100%). Conclusions: The results of the study show that subamputations with devascularisation, clinically presented with the combination of flexor tendon as the only element of tissue continuity and dislocation or minimal bone/articular injury, have a worse prognosis because of their trauma mechanism. We propose to add them to the Kay-Adani Classification as a subset of the poorest prognostic injuries group (III), to help surgeons to make decisions about the management of subamputation finger injuries.

Tamai zone -I and -II replantation versus reconstruction with local flaps: retrospective analysis for functional and cosmetic results.

A retrospective study were presented to compare functional and cosmetic outcomes in relation to local flap reconstruction or fingertip replantation in cases of zones I and II amputation. Outcomes were evaluated using Semmens Weinstein monofilament, Weber DiskCriminator, total active motion (TAM) assessment and Michigan Hand Questionnaire after a 1-year follow-up.

Bilobed skin paddle fibula flap for large oromandibular defects.

Although the fibula free flap (FFF) is a useful choice for mandible reconstruction, its application for large oromandibular defects is still debated upon. We report the use of FFF with a bilobed perforator-based skin paddle for combined hemiglossectomy, floor-of-the-mouth, tonsillar pillar, and mandibular body defect. A case of an 84-year-old woman with a 2.5 × 3.5-cm exophytic ulcerated mass on the right side of the tongue, extended to omolateral gengival fornix, tonsillar pillar, and mandibular body, is reported. An osteocutaneus FFF with a 7-cm bone strut and a 17 × 10-cm bilobed shaped skin paddle was performed. The longer lobe was used to restore tongue shape, whereas the smaller lobe was used to line the pelvic floor, gingival, and tonsillar pillar. The postoperative period was uneventful. The patient was capable to protrude her neotongue beyond the virtual incisors line and to touch the hard palate at different degrees of mouth opening. The bilobed perforator-based skin paddle FFF is felt to be a sound option for large compound oromandibular defects offering the possibility to safely base the skin component on a single peroneal perforator while achieving effective tongue mobility preservation.

Prefrontal alterations in Parkinson's disease with levodopa-induced dyskinesia during fMRI motor task.

Levodopa-induced dyskinesia represents disabling complication of long-term therapy with dopaminergic drugs in treating Parkinson's disease (PD). Recently, our group demonstrated that PD patients with levodopa-induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevance of this structural abnormality was explored using functional magnetic resonance imaging. Ten dyskinetic PD patients and 10 nondyskinetic PD patients were studied in the OFF phase with functional magnetic resonance imaging while performing externally and internally triggered visuomotor tasks. Although neither group demonstrated behavioral differences during execution of motor tasks, magnetic resonance imaging analysis detected significant changes in target cortical regions. In particular, PD patients with levodopa-induced dyskinesia showed significant overactivity in the supplementary motor area and underactivity in the right inferior prefrontal gyrus during execution of both tasks when compared with PD patients without levodopa-induced dyskinesia. Moreover, these prefrontal functional alterations were significantly correlated with Abnormal Involuntary Movement Scale scores. This functional magnetic resonance imaging study together with our previous volumetric findings highlights the role of the prefrontal cortex in the neuronal mechanisms of dyskinesia.

Brachioradialis Muscle Tendon Transposition in Extensor Pollicis Longus Reconstruction: Anatomical Study and a New Surgical Approach.

BACKGROUND: Complete extension of the thumb and activation of the extensor pollicis longus (EPL) tendon are fundamental to ensure maximum function. Many EPL repair techniques are described in the literature. METHODS: The authors present an alternative technique using the brachioradialis (BR) tendon. Thirty patients with injuries of the EPL tendon in zone 8 were studied. In all cases, neither direct suture repair nor traditional tendon transfer was possible. RESULTS: Thumb extension was restored in all patients with satisfactory extension recovery. All patients achieved excellent extension; good functional results were observed in 2 cases, and in 1 case satisfactory results were achieved using the Geldmacher assessment and the Kapandji assessment. The overall results were rated as excellent, good, fair, or poor according to the Quick Disabilities of the Arm, Shoulder, and Hand Scale. DISCUSSION: The BR tendon was suitable to treat all cases, in particular injuries occurring near Lister's tubercle, due to its appropriate length for tenorrhaphy albeit with a short distal head.

Increased prefrontal volume in PD with levodopa-induced dyskinesias: a voxel-based morphometry study.

Levodopa-induced dyskinesias represent disabling complications from long-term therapy with dopaminergic drugs for treating Parkinson's disease (PD). Although several neuroimaging studies have reported altered striatofrontal function that contributes to the emergence of these motor complications, the neuroanatomical correlates of this disorder are still unknown. Optimized voxel-based morphometry (VBM) was applied to the MRI brain images of 36 PD patients with levodopa-induced dyskinesias, 36 PD patients without levodopa-induced dyskinesias, and 32 age- and sex-matched controls. The VBM analysis comparing dyskinetic and nondyskinetic groups provided evidence of increased gray matter volume of the bilateral inferior frontal gyrus in dyskinetic patients, a finding that was more evident in patients with early-onset PD. No significant differences were detected in the dyskinetic and nondyskinetic groups when compared with the controls. Our findings suggest that the presence of dyskinesias in patients with PD is characterized by an aberrant neural plasticity that could play a role in the pathophysiology of these motor complications.

Voluptuary habits and clinical subtypes of Parkinson's disease: the FRAGAMP case-control study.

We evaluated the possible association between smoking, coffee drinking, and alcohol consumption and Parkinson's disease (PD). The FRAGAMP study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Adjusted ORs were estimated using unconditional logistic regression. Smoking, coffee, and alcohol consumption were also considered as surrogate markers of lifestyle and analysis was carried out considering the presence of at least one, two, or three factors. This latter analysis was separately performed considering Tremor-Dominant (TD) and Akinetic-Rigid (AR) patients. Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. Multivariate analysis showed a significant negative association between PD and cigarette smoking (OR 0.51; 95%CI 0.36-0.72), coffee drinking (OR 0.61; 95%CI 0.43-0.87) and wine consumption (OR 0.62; 95%CI 0.44-0.86); a significant trend dose-effect (P < 0.05) has been found for all the factors studied. We have also found a trend dose-effect for the presence of at least one, two or three factors with a greater risk reduction (83%) for the presence of three factors. However, a different strength of association between TD and AR was found with a greater risk reduction for the AR patients. We found a significant inverse association between PD smoking, coffee, and alcohol consumption. When analysis was carried out considering the association of these factors as possible surrogate markers of a peculiar lifestyle the association was stronger for the AR phenotype.

The FRAGAMP study: environmental and genetic factors in Parkinson's disease, methods and clinical features.

The Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson (FRAGAMP) study is a multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in Parkinson's disease (PD). Cases and controls were enrolled from five Movement Disorder centers in Central-Southern Italy. PD was diagnosed according to Gelb's criteria while the control groups consisted of the spouses of the enrolled patients or of healthy controls matched by age and area of residence. Cases and controls underwent a standardised questionnaire and a blood sample was taken for molecular analyses. At the end of the study 585 cases and 481 control subjects (287 spouse-controls and 194 generic-controls) were enrolled. Patients had a Hoehn-Yahr score of 2.3 +/- 0.8; 85% of them took levodopa and 47% had motor complications. The FRAGAMP study represents one of the largest case-control studies carried out in Europe to investigate the possible role of environmental and genetic factors in PD.

Propeller Flaps for Hand and Digit Reconstruction.

The reconstruction of soft tissue defects of the hand, as seen often after trauma or tumor excision, is a challenge due to the great differentiation of tissues depending on the hand area involved. The classical intrinsic "workhorse flaps" of the hand are associated with a significant donor-site morbidity. Capturing perforator vessels in discrete donor areas can reduce the amount of soft tissue that has to be dissected and included in what now would be a perforator flap, while also insuring robust vascularization of those transferred tissues. Moreover, the presence of perforator vessels both on the dorsal and volar sides of the hand allows harvest of perforator flaps that will respect the like-with-like principle by maintaining the main characteristics of volar and dorsal skin as desired. However, the dissection of these flaps, especially those based on volar palmar and digital perforators, still requires microsurgical skills to preserve the fine vascularization of these flaps. These small flaps are also amenable for application of the propeller flap concept. This is an especially valuable means for preserving the length of an amputated finger where bone is exposed by using more proximal uninjured tissues. Although in general only a short dissection is required to raise a propeller flap in this region, most often the donor site will have to be closed by a skin graft.

Critical analysis of the value of the rabbit median nerve model for biomedical research on peripheral nerve grafts.

The rabbit has been proposed to represent an animal model that allows studying peripheral nerve regeneration across extended gap lengths. We describe here our experiences with the rabbit median nerve model and the obstacles it comes along with. This short communication is meant to inform the community and to prevent other researcher from investing time and animal lives in a model with low translational power.

HOMER1 promoter analysis in Parkinson's disease: association study with psychotic symptoms.

AIMS: HOMER1 gene expression has been linked to abnormal movements in animals receiving chronic administration of antipsychotics. The continuing neurodegeneration of Parkinson's disease (PD) and the prolonged use of L-dopa are associated with motor complications, such as dyskinesia, and psychotic side effects, including hallucinations and paranoid delusions. Approximately 25-40% of patients with idiopathic PD experience hallucinations. Genetic variability within different candidate genes has been implicated in the clinical severity of sporadic PD in many populations. MATERIALS AND METHODS: We investigated 3 polymorphisms located in the 5' flanking region of the HOMER1 gene within a sample of 131 sporadic PD patients from southern Italy, using a 3-SNP genotype and haplotype combination (rs4704559, rs10942891, rs4704560). RESULTS: Our study implicates the effects of allele A of the rs4704559 marker in susceptibility to psychotic symptoms in PD (chi2 = 8.092, 1 d.f., p = 0.004). CONCLUSION: Even though our results are preliminary, this HOMER1 gene variant may represent a biomarker for side effect evaluation in PD patients.

The Median Nerve Injury Model in Pre-clinical Research - A Critical Review on Benefits and Limitations.

The successful introduction of innovative treatment strategies into clinical practise strongly depends on the availability of effective experimental models and their reliable pre-clinical assessment. Considering pre-clinical research for peripheral nerve repair and reconstruction, the far most used nerve regeneration model in the last decades is the sciatic nerve injury and repair model. More recently, the use of the median nerve injury and repair model has gained increasing attention due to some significant advantages it provides compared to sciatic nerve injury. Outstanding advantages are the availability of reliable behavioural tests for assessing posttraumatic voluntary motor recovery and a much lower impact on the animal wellbeing. In this article, the potential application of the median nerve injury and repair model in pre-clinical research is reviewed. In addition, we provide a synthetic overview of a variety of methods that can be applied in this model for nerve regeneration assessment. This article is aimed at helping researchers in adequately adopting this in vivo model for pre-clinical evaluation of peripheral nerve reconstruction as well as for interpreting the results in a translational perspective.

MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy.

PURPOSE: To prospectively assess sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) for differentiating progressive supranuclear palsy (PSP) from Parkinson disease (PD) and Parkinson variant of multiple system atrophy (MSA-P), with established consensus criteria as reference standard. MATERIALS AND METHODS: All study participants provided informed consent; study was approved by the institutional review board. Pons area, midbrain area, MCP width, and SCP width were measured in 33 consecutive patients with PSP (16 possible, 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 healthy control participants on T1-weighted MR images. The pons area-midbrain area ratio (P/M) and MCP width-SCP width ratio (MCP/SCP) were also used, and an index termed MR parkinsonism index was calculated [(P/M).(MCP/SCP)]. Differences in MR imaging measurements among groups were evaluated with Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction. RESULTS: Midbrain area and SCP width in patients with PSP (23 men, 10 women; mean age, 69.3 years) were significantly (P < .001) smaller than in patients with PD (62 men, 46 women; mean age, 65.8 years), patients with MSA-P (five men, 14 women; mean age, 64.0 years), and control participants (25 men, 25 women; mean age, 66.6 years). P/M and MCP/SCP were significantly larger in patients with PSP than in patients in other groups and control participants. All measurements showed some overlap of values between patients with PSP and patients from other groups and control participants. MR parkinsonism index value was significantly larger in patients with PSP (median, 19.42) than in patients with PD (median, 9.40; P < .001), patients with MSA-P (median, 6.53; P < .001), and control participants (median, 9.21; P < .001), without overlap of values among groups. No patient with PSP received a misdiagnosis when the index was used (sensitivity and specificity, 100%). CONCLUSION: The MR parkinsonism index can help distinguish patients with PSP from those with PD and MSA-P on an individual basis.

A new MR imaging index for differentiation of progressive supranuclear palsy-parkinsonism from Parkinson's disease.

INTRODUCTION: Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD. METHODS: Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images. RESULTS: The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients. CONCLUSION: The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo.

Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease.

The dopaminergic modulation of prefrontal function in Parkinson's disease (PD) has been consistently demonstrated. There is evidence that the effects of pharmacological manipulations on cognitive performances are described by an "Inverted-U" shaped curve. Neuroimaging studies performed before and after an overnight withdrawal from therapy showed significant differences between drug states, but did not control for the relative impact of the long duration response to levodopa. Here we evaluate the brain response after a complete pharmacological washout by correlating dopaminergic-related changes of this response to changes in performance during cognitive interference. Twelve idiopathic PD patients were studied with functional MRI while performing a modified version of the Stroop task. Patients were scanned twice: (1) following a prolonged washout procedure ("OFF" state) and (2) 90-120 min after the administration of levodopa ("ON" state). Task-related changes of PD patients were compared to those of matched healthy controls. Healthy controls displayed prefrontal and parietal responses that were positively correlated with task accuracy. In the "OFF" state, PD patients showed significant responses in anterior cingulate and pre-supplementary motor area, which are hypothesized to operate at a higher level of basal dopaminergic modulation. Levodopa administration attenuated such responses and enhanced the response of prefrontal cortex (PFC), which was correlated with improved accuracy. Results demonstrate that the behavioral effects of pharmacological manipulations of the dopamine system are highly dependent on the baseline status of PFC. When a true hypodopaminergic state is induced in PD patients, cognitive interference might significantly benefit from the administration of levodopa via an enhanced PFC response.

Hormonal replacement therapy in women with Parkinson disease and levodopa-induced dyskinesia: a crossover trial.

Eleven postmenopausal women with Parkinson disease and levodopa-induced peak-dose dyskinesias underwent a double-blind, placebo-controlled, crossover study. The active treatment consisted of estrogen replacement therapy for 12 weeks, followed by medroxyprogesterone acetate for 2 weeks. Estrogen replacement therapy-medroxyprogesterone acetate administration significantly improved peak-dose dyskinesia without worsening motor disability, thus suggesting a possible benefit on dyskinesias in postmenopausal women with Parkinson disease.

Irreversible changes occurring in long-term denervated Schwann cells affect delayed nerve repair.

OBJECTIVE Multiple factors may affect functional recovery after peripheral nerve injury, among them the lesion site and the interval between the injury and the surgical repair. When the nerve segment distal to the lesion site undergoes chronic degeneration, the ensuing regeneration (when allowed) is often poor. The aims of the current study were as follows: 1) to examine the expression changes of the neuregulin 1/ErbB system during long-term nerve degeneration; and 2) to investigate whether a chronically denervated distal nerve stump can sustain nerve regeneration of freshly axotomized axons. METHODS This study used a rat surgical model of delayed nerve repair consisting of a cross suture between the chronically degenerated median nerve distal stump and the freshly axotomized ulnar proximal stump. Before the suture, a segment of long-term degenerated median nerve stump was harvested for analysis. Functional, morphological, morphometric, and biomolecular analyses were performed. RESULTS The results showed that neuregulin 1 is highly downregulated after chronic degeneration, as well as some Schwann cell markers, demonstrating that these cells undergo atrophy, which was also confirmed by ultrastructural analysis. After delayed nerve repair, it was observed that chronic degeneration of the distal nerve stump compromises nerve regeneration in terms of functional recovery, as well as the number and size of regenerated myelinated fibers. Moreover, neuregulin 1 is still downregulated after delayed regeneration. CONCLUSIONS The poor outcome after delayed nerve regeneration might be explained by Schwann cell impairment and the consequent ineffective support for nerve regeneration. Understanding the molecular and biological changes occurring both in the chronically degenerating nerve and in the delayed nerve repair may be useful to the development of new strategies to promote nerve regeneration. The results suggest that neuregulin 1 has an important role in Schwann cell activity after denervation, indicating that its manipulation might be a good strategy for improving outcome after delayed nerve repair.