[Predictive Factors and Treatment of Aseptic Pseudoarthrosis of the Humeral Shaft]. / Prediktívne faktory a liecba aseptickej pseudoartrózy diafýzy humeru.

PURPOSE OF THE STUDY Aseptic pseudoarthrosis (nonunion, PSA) of the humeral shaft is one of the serious complications in the treatment of fractures in this area. In a retrospective study, the authors described different methods of treating patients with this complication using predictive factors. MATERIAL AND METHODS Based on the definition of nonunion and the criteria, 14 patients (N=14) with the mean age of 56 years (32-78), namely 8 men and 6 women were included in the study. All patients were followed up clinically and radiologically at 1, 3, 6, 9, 12 months and every 3 months until the condition stabilized. The follow-up period was 11-72 months, with the average of 22 months. According to the AO classification, the fractures were classified as: 4-A1, 1-A2, 4-A3, 1-B1, 3-B2 and 1-C2. Based on the Weber-Cech classification, 2 cases of pseudoarthrosis were hypertrophic, 4 oligotrophic and 8 atrophic. According to the Non-Union Scoring System (NUSS), 5 patients reached the score under 25 points, 3 patients received 25-50 points, 4 patients 51-75 points and two patients over 76 points. In five cases, the fracture displacement index (FDI) was above 100%. In 11 patients, PSA was in the proximal and middle third and in three patients in the distal third of the humerus. METHODS Of the whole group (N=14), the nail was used in 5 cases (36%) - in 3 cases NUSS of up to 50 points and in 2 cases over 76 points. The plate was used in 9 cases (64%). In patients with NUSS of up to 50 points - in 1 case after conservative treatment, in 1 case for augmentation of nail, in 3 cases for augmentation of Prévot nails. In 4 cases with NUSS of 51-75 points a plate was replaced. Osteosynthesis was always supplemented by Judet's decortication or resection of atrophic bone and spongioplasty by autologous graft. RESULTS Shoulder function measured by the Constant Murley score (C-M) improved from 53 to 89 points (from the range of 36-76 points to the range of 75-100 points). The function of the elbow joint also improved, namely from the Mayo Elbow Performance Score (MEPS) of 65 points to 90 points (from the range of 45-70 points to the range of 80-100 points). In 11 cases (79%) the nonunion was healed and in 3 cases (21%) the failure to heal was reported. In the group with unhealed nonunions, in one case with NUSS of 51-75 points a thermoplastic casting was used and in two patients with NUSS above 76 points a palliative surgery was performed using a 12mm interlocking intramedullary nail. DISCUSSION The results of our study focused on the treatment of aseptic nonunion of the humeral shaft confirm the conclusions arrived at by other authors. As to the osteosynthesis materials, the plate remains the gold standard and provides sufficient stability for bone healing. For unhealed treatment-resistant PSA, we offer a stable intramedullary nail instead of prosthetic replacement or amputation, which provides good stability required for limb function. CONCLUSIONS When planning the treatment of aseptic pseudoarthrosis of the humeral shaft, it is necessary to have a thorough knowledge of etiopathogenesis with all predictive factors. The NUSS classification provides good guidance in treating this complication. Key words: aseptic nonunion, NUSS classification, predictive factors.

Case series of congenital pseudarthrosis of the tibia unfulfilling neurofibromatosis type 1 diagnosis: 21% with somatic NF1 haploinsufficiency in the periosteum.

Up to 84% of patients with congenital pseudarthrosis of the tibia (CPT) present with neurofibromatosis type 1 (NF1) (NF1-CPT). However, the etiology of CPT not fulfilling the NIH diagnostic criteria for NF1 (non-NF1-CPT) is not well understood. Here, we collected the periosteum tissue from the pseudarthrosis (PA) site of 43 non-NF1-CPT patients and six patients with NF1-CPT, together with the blood or oral specimen of trios (probands and unaffected parents). Whole-exome plus copy number variation sequencing, multiplex ligation-dependent probe amplification (MLPA), ultra-high amplicon sequencing, and Sanger sequencing were employed to identify pathogenic variants. The result showed that nine tissues of 43 non-NF1-CPT patients (21%) had somatic mono-allelic NF1 inactivation, and five of six NF1-CPT patients (83.3%) had bi-allelic NF1 inactivation in tissues. However, previous literature involving genetic testing did not reveal somatic mosaicism in non-NF1-CPT patients so far. In NF1-CPT patients, when the results from earlier reports and the present study were combined, 66.7% of them showed somatic NF1 inactivation in PA tissues other than germline inactivation. Furthermore, no diagnostic variants from other known genes (GNAS, AKT1, PDGFRB, and NOTCH3) related to skeletal dysplasia were identified in the nine NF1 positive non-NF1-CPT patients and six NF1-CPT patients. In conclusion, we detected evident somatic mono-allelic NF1 inactivation in the non-NF1-CPT. Thus, for pediatric patients without NF1 diagnosis, somatic mutations in NF1 are important.

Pseudarthrosis and Rod Fracture Rates After Transforaminal Lumbar Interbody Fusion at the Caudal Levels of Long Constructs for Adult Spinal Deformity Surgery.

BACKGROUND: Interbody fusion at the caudal levels of long constructs for adult spinal deformity (ASD) surgery is used to promote fusion and secure a solid foundation for maintenance of deformity correction. We sought to evaluate long-term pseudarthrosis, rod fracture, and revision rates for TLIF performed at the base of a long construct for ASD. METHODS: We reviewed 316 patients who underwent TLIF as a component of ASD surgery for medical comorbidities, surgical characteristics, and rate of unplanned reoperation for pseudarthrosis or instrumentation failure at the TLIF level. Fusion grading was assessed after revision surgery for pseudarthrosis at the TLIF level. RESULTS: Rate of pseudarthrosis at the TLIF level was 9.8% (31/316), and rate of rod fractures was 7.9% (25/316). The rate of revision surgery at the TLIF level was 8.9% (28/316), and surgery was performed at a mean of 20.4 ± 16 months from the index procedure. Current smoking status (odds ratio 3.34, P = 0.037) was predictive of pseudarthrosis at the TLIF site. At a mean follow-up of 43 ± 12 months after revision surgery, all patients had achieved bony union at the TLIF site. CONCLUSIONS: At 3-year follow-up, the rate of pseudarthrosis after TLIF performed at the base of a long fusion for ASD was 9.8%, and the rate of revision surgery to address pseudarthrosis and/or rod fracture was 8.9%. All patients were successfully treated with revision interbody fusion or posterior augmentation of the fusion mass, without need for further revision procedures at the TLIF level.

Association of osteopenia and osteoporosis with higher rates of pseudarthrosis and revision surgery in adult patients undergoing single-level lumbar fusion.

OBJECTIVE: Patients with osteopenia or osteoporosis who require surgery for symptomatic degenerative spondylolisthesis may have higher rates of postoperative pseudarthrosis and need for revision surgery than patients with normal bone mineral densities (BMDs). To this end, the authors compared rates of postoperative pseudarthrosis and need for revision surgery following single-level lumbar fusion in patients with normal BMD with those in patients with osteopenia or osteoporosis. The secondary outcome was to investigate the effects of pretreatment with medications that prevent bone loss (e.g., teriparatide, bisphosphonates, and denosumab) on these adverse outcomes in this patient cohort. METHODS: Patients undergoing single-level lumbar fusion between 2007 and 2017 were identified. Based on 1:1 propensity matching for baseline demographic characteristics and comorbidities, 3 patient groups were created: osteopenia (n = 1723, 33.3%), osteoporosis (n = 1723, 33.3%), and normal BMD (n = 1723, 33.3%). The rates of postoperative pseudarthrosis and revision surgery were compared between groups. RESULTS: The matched populations analyzed in this study included a total of 5169 patients in 3 groups balanced at baseline, with equal numbers (n = 1723, 33.3%) in each group: patients with a history of osteopenia, those with a history of osteoporosis, and a control group of patients with no history of osteopenia or osteoporosis and with normal BMD. A total of 597 complications were recorded within a 2-year follow-up period, with pseudarthrosis (n = 321, 6.2%) being slightly more common than revision surgery (n = 276, 5.3%). The odds of pseudarthrosis and revision surgery in patients with osteopenia were almost 2-fold (OR 1.7, 95% CI 1.26-2.30) and 3-fold (OR 2.73, 95% CI 1.89-3.94) higher, respectively, than those in patients in the control group. Similarly, the odds of pseudarthrosis and revision surgery in patients with osteoporosis were almost 2-fold (OR 1.92, 95% CI 1.43-2.59) and > 3-fold (OR 3.25, 95% CI 2.27-4.65) higher, respectively, than those in patients in the control group. Pretreatment with medications to prevent bone loss prior to surgery was associated with lower pseudarthrosis and revision surgery rates, although the differences did not reach statistical significance. CONCLUSIONS: Postoperative pseudarthrosis and revision surgery rates following single-level lumbar spinal fusion are significantly higher in patients with osteopenia and osteoporosis than in patients with normal BMD. Pretreatment with medications to prevent bone loss prior to surgery decreased these complication rates, although the observed differences did not reach statistical significance.

Congenital pseudarthrosis of the tibia: Results of circular external fixation treatment with intramedullary rodding and periosteal grafting technique.

OBJECTIVE: This study investigated the clinical and functional results of treating congenital pseudarthrosis of the tibia (CPT) using the combined techniques of hamartoma resection, periosteal grafting, circular external fixator application, and intramedullary rodding. METHODS: The clinical and radiological data of 17 patients (mean age at the treatment time: 7.6 months (range: 4.6-9.7 months) with CPT, treated by a single surgeon between 1997 and 2017, were retrospectively analyzed. All data regarding surgical interventions, complications, deformity analysis parameters, limb length discrepancy (LLD), ankle joint range of motion, and residual deformities were reviewed. All the patients were followed up at least two years after the last surgical intervention. The mean follow-up time was 8.5 years (range: 2.2 to 15.7 years). RESULTS: Union was achieved with the index treatment in 15 of the 17 cases (88.2%). The mean age of the patients at the last follow-up visit was 14.2 years (range: 7.6 to 22.1). The mean LLD was 2.1 cm. Nine patients had radiological ankle valgus at the last follow-up. In the entire series, eight patients did not display any complications, four cases reported minor complications, and five cases were complicated by refractures. CONCLUSION: Circular external fixator application combined with periosteal grafting is a superior method of CPT treatment. This method provides a healthy biological healing environment while correcting the mechanical problems. The combination of periosteal and cancellous bone grafts with intramedullary rods and an external fixator addresses issues that complicate obtaining and maintaining a union during the CPT treatment. LEVEL OF EVIDENCE: Level IV, Therapeutic study.

Congenital pseudarthrosis of the tibia: the outcome of a pathology-oriented classification system and treatment protocol.

Congenital pseudarthrosis of the tibia is defined as a non-union of a tibial fracture that develops in a dysplastic bone segment of the tibial diaphysis. Pathologically, a fibrous hamartoma surrounds the bone at the congenital pseudarthrosis of the tibia site. The cases of 25 children, who have congenital pseudarthrosis of the tibia, were included in this study. Their ages ranged from 15 months to 15 years at the time of treatment. Neurofibromatosis-1 was present in 24 children. They were managed according to our classification system and treatment protocol. The treatment for mobile pseudarthrosis (types 1 and 2) included complete excision of the pathological periosteum, insertion of autogenous iliac crest bone graft, and combined fixation using intramedullary rod and Ilizarov external fixator. For type 3 pseudarthrosis (stiff pseudarthrosis), a pre-constructed Ilizarov fixator was applied for simultaneous distraction of the pseudarthrosis and deformity correction without open surgery. Evaluation of results was mainly radiological and included achievement of union, leg length equalization, deformity correction and prevention of refracture. Consolidation of the pseudarthrosis and osteotomies was achieved in all cases (100%). Refracture occurred in one case (4%) at the site of previous pseudarthrosis. Residual limb length discrepancy more than 2.5 cm occurred in two cases (8%). Valgus deformity of the ankle was present in 12 cases (48%) and was treated by supramalleolar osteotomy. Follow-up ranged from 24 to 48 months (average 36.9 months) after fixator removal. The results of our treatment protocol, based on our classification system, have been consistently good and predictable in all cases of congenital pseudarthrosis of the tibia. Mobility of the pseudarthrosis is an important factor in choosing the type of interference.

Identification and characterization of NF1 and non-NF1 congenital pseudarthrosis of the tibia based on germline NF1 variants: genetic and clinical analysis of 75 patients.

BACKGROUND: Congenital pseudarthrosis of the tibia (CPT) is a rare disease. Some patients present neurofibromatosis type 1 (NF1), while some others do not manifest NF1 (non-NF1). The etiology of CPT, particularly non-NF1 CPT, is not well understood. Here we screened germline variants of 75 CPT cases, including 55 NF1 and 20 non-NF1. Clinical data were classified and analyzed based on NF1 gene variations to investigate the genotype-phenotype relations of the two types of patients. RESULTS: Using whole-exome sequencing and Multiplex Ligation-Dependent Probe Amplification, 44 out of 55 NF1 CPT patients (80.0%) were identified as carrying pathogenic variants of the NF1 gene. Twenty-five variants were novel; 53.5% of variants were de novo, and a higher proportion of their carriers presented bone fractures compared to inherited variant carriers. No NF1 pathogenic variants were found in all 20 non-NF1 patients. Clinical features comparing NF1 CPT to non-NF1 CPT did not show significant differences in bowing or fracture onset, lateralization, tissue pathogenical results, abnormality of the proximal tibial epiphysis, and follow-up tibial union after surgery. A considerably higher proportion of non-NF1 patients have cystic lesion (Crawford type III) and used braces after surgery. CONCLUSIONS: We analyzed a large cohort of non-NF1 and NF1 CPT patients and provided a new perspective for genotype-phenotype features related to germline NF1 variants. Non-NF1 CPT in general had similar clinical features of the tibia as NF1 CPT. Germline NF1 pathogenic variants could differentiate NF1 from non-NF1 CPT but could not explain the CPT heterogeneity of NF1 patients. Our results suggested that non-NF1 CPT was probably not caused by germline NF1 pathogenic variants. In addition to NF1, other genetic variants could also contribute to CPT pathogenesis. Our findings would facilitate the interpretation of NF1 pathogenic variants in CPT genetic counseling.

Physeal and Subphyseal Distraction Osteogenesis in Atrophic-type Congenital Pseudarthrosis of the Tibia: Efficacy and Safety.

PURPOSE: To examine the efficacy, safety, and clinical outcomes of distraction osteogenesis through the physis (PDO) or through subphyseal osteotomy (SPDO) in patients with atrophic-type congenital pseudarthrosis of tibia with proximal tibial dysplasia. METHODS: To validate the efficacy and safety of PDO and SPDO, radiographic and clinical parameters were compared between 5 patients who underwent proximal tibial metaphyseal or metadiaphyseal lengthening as a control (group 1) and 7 patients who underwent PDO or SPDO (group 2). Postoperative complication was also compared between the groups. RESULTS: A significant difference in terms of healing index (group 1, 83.3±24.7 d/cm; group 2, 35.0±11.1 d/cm; P=0.001) and percentage increase (11.0%±3.7% vs. 23.1%±10.5%, P=0.034) was observed between the 2 groups. According to the Paley classification, group 1 included 1 "problems" case and 3 "obstacles" cases, whereas group 2 included 2 "problems" cases and 1 "obstacles" case. According to the Lascombes classification, group 1 included 2 grade IIIb cases and 3 grade IV cases, whereas group 2 included 6 grade I cases and 1 grade IIa case. Severe complications were significantly higher in group 1 compared with the group 2 (P=0.007). CONCLUSIONS: This study demonstrated that PDO or SPDO can be effectively and safely performed for tibial lengthening in atrophic-type congenital pseudarthrosis of tibia patients with proximal tibial dysplasia. LEVEL OF EVIDENCE: Level III.

Management of a pseudarthrosis with sagittal malalignment in a patient with ochronotic spondyloarthropathy.

PURPOSE: Ochronotic spondyloarthropathy is an uncommon disease, and its association to sagittal malalignment in the context of a pseudarthrosis has never been described. METHODS: We present the case of a 56-year-old female, who underwent previously L4L5 laminectomy for central canal stenosis and started later on to complain of progressively severe low back pain with a significant forward imbalance while walking. X-rays showed non-compensated sagittal malalignment due to thoracolumbar kyphosis, CT scan revealed multilevel central intradiscal calcifications with important vacuum disc at L4L5, and MRI showed T1 and T2 hypointensity signal at the same level with bone marrow oedema. Alkaptonuric ochronosis was suspected and confirmed by the presence of homogentisic acid in the urine, and the diagnosis of L4L5 pseudarthrosis with associated severe sagittal malalignment in the context of ochronotic spondyloarthropathy was established. RESULTS: The patient underwent surgery with a posterior-only approach with a long-segment pedicle screw construct from T10 to the pelvis with a 360° fusion with a cage at L4L5. Samples taken from the disc and ligaments confirmed the diagnosis of ochronotic spondyloarthropathy macroscopically and microscopically. She could walk on day 2 with a satisfactory clinical and radiological result at 2 years. CONCLUSION: This is the first case in the literature to describe a post-laminectomy pseudarthrosis leading to a significant sagittal malalignment in a patient with ochronotic spondyloarthropathy. Management of such a case is challenging as the spine is partially ankylosed; therefore, a long construct is advisable to avoid ankylosing disorders related complications.

Neurofibromatosis type 1-related pseudarthrosis: Beyond the pseudarthrosis site.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting approximately 1 in 2,000 newborns. Up to 5% of NF1 patients suffer from pseudarthrosis of a long bone (NF1-PA). Current treatments are often unsatisfactory, potentially leading to amputation. To gain more insight into the pathogenesis we cultured cells from PA tissue and normal-appearing periosteum of the affected bone for NF1 mutation analysis. PA cells were available from 13 individuals with NF1. Biallelic NF1 inactivation was identified in all investigated PA cells obtained during the first surgery. Three of five cases sampled during a later intervention showed biallelic NF1 inactivation. Also, in three individuals, we examined periosteum-derived cells from normal-appearing periosteum proximal and distal to the PA. We identified the same biallelic NF1 inactivation in the periosteal cells outside the PA region. These results indicate that NF1 inactivation is required but not sufficient for the development of NF1-PA. We observed that late-onset NF1-PA occurs and is not always preceded by congenital bowing. Furthermore, the failure to identify biallelic inactivation in two of five later interventions and one reintervention with a known somatic mutation indicates that NF1-PA can persist after the removal of most NF1 negative cells.

Recurrent unilateral peripheral facial palsy in a patient with an enlarged styloid process.

BACKGROUND: Recurrent peripheral facial paresis is a rare symptom that may be caused by multiple pathologic conditions. METHODS: We report a case of recurrent peripheral facial palsies caused by an ipsilateral enlarged styloid process. A surgical excision of the process was performed. RESULTS: The treatment was well tolerated. Postoperatively, no further recurrent paresis was observed. CONCLUSION: To the best of our knowledge, this is the first case study of an enlarged styloid process with facial paresis. A detailed workup, including imaging, should be performed in cases with recurrent facial paresis and/or cases with a history of trauma and facial paresis and, of course, to exclude a neoplastic etiology.

Pseudarthrosis in adult and pediatric spinal deformity surgery: a systematic review of the literature and meta-analysis of incidence, characteristics, and risk factors.

We conducted a systematic review with meta-analysis and qualitative synthesis. This study aims to characterize pseudarthrosis after long-segment fusion in spinal deformity by identifying incidence rates by etiology, risk factors for its development, and common features. Pseudarthrosis can be a painful and debilitating complication of spinal fusion that may require reoperation. It is poorly characterized in the setting of spinal deformity. The MEDLINE, EMBASE, and Cochrane databases were searched for clinical research including spinal deformity patients treated with long-segment fusions reporting pseudarthrosis as a complication. Meta-analysis was performed on etiologic subsets of the studies to calculate incidence rates for pseudarthrosis. Qualitative synthesis was performed to identify characteristics of and risk factors for pseudarthrosis. The review found 162 articles reporting outcomes for 16,938 patients which met inclusion criteria. In general, the included studies were of medium to low quality according to recommended reporting standards and study design. Meta-analysis calculated an incidence of 1.4% (95% CI 0.9-1.8%) for pseudarthrosis in adolescent idiopathic scoliosis, 2.2% (95% CI 1.3-3.2%) in neuromuscular scoliosis, and 6.3% (95% CI 4.3-8.2%) in adult spinal deformity. Risk factors for pseudarthrosis include age over 55, construct length greater than 12 segments, smoking, thoracolumbar kyphosis greater than 20°, and fusion to the sacrum. Choice of graft material, pre-operative coronal alignment, post-operative analgesics, and sex have no significant impact on fusion rates. Older patients with greater deformity requiring more extensive instrumentation are at higher risk for pseudarthrosis. Overall incidence of pseudarthrosis requiring reoperation is low in adult populations and very low in adolescent populations.

Congenital Clavicular Pseudoarthosis-How to Differentiate It From the More Common Clavicular Fractures.

Congenital pseudoarthrosis of the clavicle is a rare entity that can be confused for a traumatic injury. We present 4 cases of congenital clavicular pseudoarthrosis and discuss its imaging findings that can help differentiate it from the more common clavicular facture. We also reviewed its epidemiology, embryology, and management based on available and most recent literature.

Symptomatic pseudoarthrosis secondary to a stress fracture of the acromion.

Fractures of the acromion are uncommon clinical entities, and stress fractures are even more rare, with few cases reported. Due to their rarity, stress fractures are often misdiagnosed. Here, we report a case of an elderly patient with an acromion stress fracture, which was overlooked, resulting in nonunion followed by the displacement of the distal portion of the acromion. The purpose of this report was to discuss this rare fracture, highlighting the importance of an accurate evaluation of radiological imaging as well as clinical data. (www.actabiomedica.it).

Pseudoarthrosis of second metatarsal fracture.

Metatarsal fractures make up the greatest portion of foot fractures in children. Most of them are treated with closed reduction and non-weightbearing cast immobilization.Usually, these fractures heal uneventfully and delay union and pseudoarthrosis are rare. We report a case of a 10-year-old child with non-union of the second metatarsal following a traumatic fracture, caused by an accident 10 months before, and treated successfully by osteosynthesis with plate and screws. Good clinical outcome was achieved at 2 years follow-up.

Current treatment of congenital pseudarthrosis of the tibia: a systematic review and meta-analysis.

To compare the current treatments for congenital pseudarthrosis of tibia, a total of 33 studies were reviewed. Vascularized fibular graft with external fixation or combined fixation had the fastest time till initial union (P<0.05). Bone morphogenetic protein had no advantage in terms of initial union, time till union, and refracture rates. This meta-analysis supports that fixation methods with corticocancellous bone autograft utilizing the combined technique of Ilizarov external fixation and intramedullary rod stabilization ensure a statistically significant reduction in the number of refractures compared with standalone fixation methods and would be the preferred method for preventing long-term complications in patients with congenital pseudarthrosis of tibia.

Epidemiological Analysis of Major Complications Requiring Medical Intervention in Patients with Neurofibromatosis 1.

Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1.