NIVALDO ALONSO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/04 - Laboratório de Microcirurgia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/04 - Laboratório de Microcirurgia, Hospital das Clínicas, Faculdade de Medicina - Líder
15 resultados
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- Cranial Fossa Volume and Morphology Development in Apert Syndrome(2020) LU, Xiaona; FORTE, Antonio Jorge; WILSON, Alexander; STEINBACHER, Derek M.; ALPEROVICH, Michael; ALONSO, Nivaldo; PERSING, John A.Background: Apert syndrome causes normal or enlarged intracranial volume overall as patients grow. This study aimed to trace the segmental anterior, middle, and posterior cranial fossae volume and structural morphology in these patients, to help discern a more focused and individualized surgical treatment plan for patients with Apert syndrome. Methods: This study included 82 preoperative computed tomographic scans (Apert, n = 32; control, n = 50) divided into five age-related subgroups. The scans were measured using image processing and three-dimensional modeling software. Results: The middle cranial fossa volume was increased and was the earliest change noted. It was increased by 45 percent (p = 0.023) compared with controls before 6 months of age and remained increased into adulthood (161 percent, p = 0.016), with gradually increasing severity. The anterior and posterior cranial fossae volumes also increased, by 35 percent (p = 0.032) and 39 percent (p = 0.007), respectively. Increased depth of cranial fossae contributed most to the increase in volumes of patients with Apert syndrome, with correlation coefficients of 0.799, 0.908, and 0.888 for anterior, middle, and posterior cranial fossa, respectively. The intracranial volume was increased 12 percent (p = 0.098) across the entire test age range (0 to 26 years old), but only had statistical significance during the age range of 6 to 18 years (22 percent, p = 0.001). Conclusions: Malformation of the middle cranial fossa is an early, perhaps the initial, pivotal cranial morphologic change in Apert syndrome. Increased cranial fossae depth is an inherent characteristic of the maldevelopment. Normalization of cranial volume and circumference overall may not achieve a normal skull structure, as it does not correct regional craniocerebral disproportion.
- Skull Base Cephalometric Changes in Cranial Expansion by Springs(2011) DORNELLES, Rodrigo de Faria Valle; CARDIM, Vera Lucia Nocchi; PINTO, Ana Carolina Brandao de Campos Fonseca; ALONSO, NivaldoBackground: The use of springs in cranial expansion has demonstrated to be effective for craniosynostosis treatment. The spring-exerted expansile action has been observed when springs are placed both in the sagittal and parasagittal regions, mainly in scaphocephaly. In this study, a variation in cephalometric measurements under expansible spring action on the skull base was analyzed. Methods: Thirteen 4-week-old New Zealand white rabbits were divided into 4 groups: group 1, in which only amalgam markers were used (control); group 2, in which amalgam markers were used, and a sagittal suturectomy was performed; group 3, in which amalgam markers were used, and a sagittal suturectomy was performed with placement of expansible springs in the interparietal region; and group 4, in which markers were used, and a linear parasagittal craniectomy was performed with spring placement. All animals were killed at weeks 2, 4, 8, and 12. Radiologic control with cephalometric study was performed. Results: Distraction of amalgam markers in the groups with springs was greater than in those without springs. A proportional change in the angles measured through craniometry was observed in these groups. Conclusions: The experimental rabbit model was shown to be adequate to the analysis proposed by the study. Under the action of springs, the groups with sagittal and parasagittal osteotomy were found to present a similar distraction of amalgam markers. A concomitant change in cephalometric measurements occurred, suggesting a change in the skull base mediated by expansible springs placed both in the sutural and nonsutural sites.
- Normal angulation of skull base in Apert syndrome(2018) LU, Xiaona; FORTE, Antonio Jorge; SAWH-MARTINEZ, Rajendra; WU, Robin; CABREJO, Raysa; STEINBACHER, Derek M.; ALPEROVICH, Michael; ALONSO, Nivaldo; PERSING, John A.Apert syndrome is characterized by the severe craniofacial deformities. The subsequent process of skeletal maldevelopment is likely to be influenced by multiple interactions at several levels, at a given time. In this study, we aimed to explore the evolution of cranial basal dysmorphology and the chronology of these deformities in Apert syndrome, by objectively analyzing three-dimensional measurements. Fifty-four CT scans from unoperated patients (Apert, n = 18; control, n = 36) were included in this study, with age range from 3 days to 24 years. Before 6 months of age, Apert's anterior cranial base was widened 60%. Between 6 months and 2 years of age, the whole cranial base length, anterior cranial base length and posterior cranial base length decreased 8%, 8% and 14%, respectively. The greater sphenoid wing angle was wider by 26.0 degrees, and continued into adulthood. The cranial base angles did not produce significant changes throughout life. The extra cranial distances synchronously and almost proportionally shortened after later infancy. The anterior and posterior cranial base length shortened at an almost proportional rate. The malformations of the skull vault are additive effects with cranial base fusion on skull length restriction, but the angulation of the skull base is virtually normal.
- What Is the Difference in Cranial Base Morphology in Isolated and Syndromic Bicoronal Synostosis?(2020) LU, Xiaona; FORTE, Antonio Jorge; WILSON, Alexander T.; PARK, Kitae Eric; ALLAM, Omar; MOZAFFARI, Mohammad Ali; ALPEROVICH, Michael; STEINBACHER, Derek M.; ALONSO, Nivaldo; PERSING, John A.Background: The association of isolated craniosynostosis and the influence of syndromic forms confound the understanding of craniofacial morphologic development. This study attempts to clarify the individual influences of isolated bicoronal synostosis, Apert syndrome, and Crouzon syndromes on skull base morphology. Methods:: One hundred seventeen computed tomographic scans were included (nonsyndromic bicoronal synostosis,n= 36; Apert syndrome with bicoronal synostosis,n= 25; Crouzon syndrome with bicoronal synostosis,n= 11; controls,n= 45). Cephalometric measurements were analyzed using Materialise software. Results: Nonsyndromic bicoronal synostosis patients developed a shortened cranial base length, with a significantly shortened distance between nasion and sella (p= 0.005). The cranial base angles of nonsyndromic bicoronal synostosis in both the cranial side (N-S-BA) and facial side (N-SO-BA) increased significantly, by 17.04 degrees (p <0.001) and 11.75 degrees (p <0.001), respectively. However, both the N-S-BA and N-SO-BA angles of Apert syndrome and Crouzon syndrome were narrowed more than that of nonsyndromic bicoronal synostosis [by 12.11 degrees (p <0.001) and 12.44 degrees (p <0.001), respectively, in Apert syndrome; and by 11.66 degrees (p= 0.007) and 13.71 degrees (p= 0.007), respectively, in Crouzon syndrome]. However, there is no statistically significant difference of these two angles between Apert syndrome and Crouzon syndrome, when they were only associated with bicoronal synostosis. Contrary to the relatively normal subcranial space of nonsyndromic bicoronal synostosis, both Apert and Crouzon syndromes developed a reduced subcranial space. Conclusions: Isolated bicoronal synostosis resulted in a flattened cranial base, whereas Apert syndrome and Crouzon syndrome developed a normal cranial base angle when only associated with bicoronal synostosis. The syndromic skulls had additional significantly reduced subcranial space.
- FGFR2 Mutation Confers a Less Drastic Gain of Function in Mesenchymal Stem Cells Than in Fibroblasts(2012) YEH, Erika; ATIQUE, Rodrigo; ISHIY, Felipe A. A.; FANGANIELLO, Roberto Dalto; ALONSO, Nivaldo; MATUSHITA, Hamilton; ROCHA, Katia Maria da; PASSOS-BUENO, Maria RitaGain-of-function mutations in FGFR2 cause Apert syndrome (AS), a disease characterized by craniosynostosis and limb bone defects both due to abnormalities in bone differentiation and remodeling. Although the periosteum is an important cell source for bone remodeling, its role in craniosynostosis remains poorly characterized. We hypothesized that periosteal mesenchymal stem cells (MSCs) and fibroblasts from AS patients have abnormal cell phenotypes that contribute to the recurrent fusion of the coronal sutures. MSCs and fibroblasts were obtained from the periostea of 3 AS patients (S252W) and 3 control individuals (WT). We evaluated the proliferation, migration, and osteogenic differentiation of these cells. Interestingly, S252W mutation had opposite effects on different cell types: S252W MSCs proliferated less than WT MSCs, while S252W fibroblasts proliferated more than WT fibroblasts. Under restrictive media conditions, only S252W fibroblasts showed enhanced migration. The presence of S252W mutation increased in vitro and in vivo osteogenic differentiation in both studied cell types, though the difference compared to WT cells was more pronounced in S252W fibroblasts. This osteogenic differentiation was reversed through inhibition of JNK. We demonstrated that S252W fibroblasts can induce osteogenic differentiation in periosteal MSCs but not in MSCs from another tissue. MSCs and fibroblasts responded differently to the pathogenic effects of the FGFR2(S252W) mutation. We propose that cells from the periosteum have a more important role in the premature fusion of cranial sutures than previously thought and that molecules in JNK pathway are strong candidates for the treatment of AS patients.
- Morphological Basis for Airway Surgical Intervention in Apert Syndrome(2021) LU, Xiaona; FORTE, Antonio Jorge; PARK, Kitae Eric; ALLAM, Omar; ALPEROVICH, Michael; STEINBACHER, Derek M.; TONELLO, Cristiano; ALONSO, Nivaldo; PERSING, John A.Objective Previous studies have explored the restricted nasopharyngeal airway in Apert syndrome patients. This study aims to investigate the segmented airway volume changes with age and directly analyze their correlations with subcranial dimensions and angulations. Methods Ninety-seven preoperative computed tomography scans (Apert, n = 44; control, n = 53) were included in this study, and divided into 5 age-related subgroups. Computed tomography scans were measured using Mimics and 3-matics software. Results Before 6 months of age, the nasal cavity in Apert syndrome is reduced by 47% (P = 0.002), which gradually approximates normal thereafter; however, there remained a 30% reduction, compared with controls. It is highly correlated with the anteroposterior length of subcranial space, and the position of maxilla and palate. The pharyngeal airway volume in Apert syndrome patients, younger than 6 months, was larger than normal by 129% (P = 0.013). However, between 2 and 6 years of age, the pharyngeal airway becomes smaller than normal, with a 57% (P = 0.010) reduction in childhood and 52% (P = 0.005) in adolescence. It is closely correlated with the intercondylar and intergonial widths. Conclusions Airway compromise in Apert syndrome patients is attributable more to the nasal cavity in infants, but in the older child, it is the pharyngeal region. The restricted nasal airway in Apert syndrome is correlated with the subcranial space length and width, but independent of cranial base flexion. The pharyngeal airway volume in Apert syndrome is not as highly correlated with craniofacial morphology. Rather, it is impacted by the growth of mandible, which often requires surgical intervention later in childhood.
- Frontal-orbital advancement for the management of anterior plagiocephaly(2012) MATUSHITA, Hamilton; ALONSO, Nivaldo; CARDEAL, Daniel Dante; ANDRADE, Fernanda deThe main purposes of this manuscript are to provide an overview of various modalities of surgical correction of anterior plagiocephaly and to emphasize their differences with the classic open frontal-orbital advancement. Advancement of technology provides development of many other ways to achieve the same results. The authors describe the classic open frontal-orbital advancement and compare with other proposed techniques for correction of frontal plagiocephaly. The main limitation of the use of new forms of treatment of the anterior plagiocephaly is the age of the patient. There is still no consensus on criteria for quantitative evaluation of surgical results, and new forms of treatment do not present results with long follow-up. Frontal-orbital advancement is the preferred procedure to correct unicoronal synostosis due to its universal indication regardless of the age and degree of deformation of the anterior plagiocephaly.
- Orbital and Periorbital Dysmorphology in Untreated Pfeiffer Syndrome(2022) LU, Xiaona; FORTE, Antonio Jorge; ALLAM, Omar; PARK, Kitae Eric; WILSON, Alexander; ALPEROVICH, Michael; STEINBACHER, Derek M.; TONELLO, Cristiano; ALONSO, Nivaldo; PERSING, John A.Background: Visual impairment secondary to orbital and periorbital dysmorphology is frequent in Pfeiffer syndrome patients. The etiopathogenesis of this aberrancy, however, remains unclear. Methods: Untreated Pfeiffer syndrome patients (n = 31) and normal control subjects (n = 43) were compared. Craniometric and volumetric analyses related to the orbital and periorbital anatomy were performed using Materialise (Leuven, Belgium) software. Results: Overall, orbital cavity volume of Pfeiffer patients is reduced by 28 percent (p < 0.001), compared to normal, starting before 3 months of age (p = 0.004). Globe volume was diminished by 10 percent (p = 0.041) before 3 months of age, yet tended to catch up thereafter. However, the retrobulbar soft-tissue volume remained smaller beyond 1 year of age (17 percent, p = 0.003). Globe volume projection beyond the bony orbit increased in all observed ages (82 percent, p < 0.001). The volumes of sphenoid bone, maxilla, and mandible proportionately were restricted by 24 to 25 percent (p = 0.003 to 0.035) before 3 months of age. The volume of maxilla and mandible gradually approximate normal; however, the sphenoid bone volume in Pfeiffer patients remains less than normal (p = 0.002) into childhood. The anteroposterior length of both the zygoma and the maxilla was reduced by 14 percent (p < 0.001). Anterior positioning of the zygoma is less by 23 percent (p < 0.001) in Pfeiffer patients overall, with anterior positioning of maxilla reduced similarly by 23 percent (p < 0.001). Conclusions: Pfeiffer syndrome patients develop decreased retrobulbar soft-tissue and globe volume, along with a restricted orbital cavity volume in infancy. Significant hypoplasia of the sphenoid bone is associated with more severe central facial (maxilla) retrusion, compared to lateral facial structures (zygoma).
- Orbitofacial morphology changes with different suture synostoses in Crouzon syndrome(2022) LU, Xiaona; FORTE, Antonio Jorge; JUNN, Alexandra; DINIS, Jacob; ALPEROVICH, Michael; ALONSO, Nivaldo; PERSING, John A.This study aims to investigate the influence of different cranial vault suture synostoses on orbital and periorbital morphological development in Crouzon syndrome. Computed tomography (CT) scans of Crouzon syndrome patients who had not undergone operation were subgrouped as follows: type I: bicoronal synostosis; type II: sagittal synostosis; type III: pansynostosis; type IV: perpendicular combinations of suture synostoses; and type V: bilateral squamosal synostosis. CT scans were measured using Materialise software. CT scans of 80 Crouzon syndrome patients and 72 normal controls were included. Orbital bony cavity volume was reduced in all subgroups (16-24%), including type V bilateral squamosal synostosis (16%, p = 0.003), although the reduction in type II sagittal synostosis Crouzon patients failed to reach statistical significance (p = 0.071). Globe volume was reduced only in type I bicoronal synostosis (9%, p = 0.018), while the retrobulbar soft tissue volume decreased in type III pansynostosis group by 11% (p = 0.005). Globe volume projection beyond the orbital rim was increased in all groups (p < 0.001), with the greatest increase in type IV perpendicular combination of sutures synostoses, by 100% (p < 0.001). The anteroposterior length of maxilla was significantly shortened in type I (10%, p = 0.028) and type III (9%, p = 0.022) but developed normally in other groups, although the maxilla was posteriorly displaced in all groups (all p <= 0.026). The influence of squamosal synostosis on craniofacial malformation is not equivalent to that of a major vault suture. Therefore, subtype suture fusion individualized surgical interventions, after initial occipital expansion, likely provide additional benefits in mitigating oculo-orbital disproportion.
- Classification of Subtypes of Apert Syndrome, Based on the Type of Vault Suture Synostosis(2019) LU, Xiaona; SAWH-MARTINEZ, Rajendra; FORTE, Antonio Jorge; WU, Robin; CABREJO, Raysa; WILSON, Alexander; STEINBACHER, Derek M.; ALPEROVICH, Michael; ALONSO, Nivaldo; PERSING, John A.Background: Apert syndrome patients are different in clinical pathology, including obstructive sleep apnea, cleft palate, and mental deficiency. These functional deficiencies may be due to anatomic deformities, which may be caused by different forms of associated suture fusion. Therefore, a classification system of Apert syndrome based on the type of craniosynostosis pattern might be helpful in determining treatment choices. Methods: CT scans of 31 unoperated Apert syndrome and 51 controls were included and subgrouped as: class I. Bilateral coronal synostosis; class II. Pansynostosis; and class III. Perpendicular combination synostosis: a. unilateral coronal and metopic synostosis; b. sagittal with bilateral/unilateral lambdoid synostosis; and c. others. Results: Class I is the most common (55%) subtype. The cranial base angulation of class I was normal; however, the cranial base angulation on the cranium side of the skull in class II increased 12.16 degrees (P = 0.006), whereas the facial side cranial base angle of class IIIa decreased 4.31 degrees (P = 0.035) over time. The external cranial base linear measurements of class I showed more evident reduction in anterior craniofacial structures than posterior, whereas other subtypes developed more severe shortening in the posterior aspects. Conclusions: Bicoronal synostosis is the most common subtype of Apert syndrome with the normalized cranial base angulation. Combined pansynostosis patients have flatter cranial base, whereas the combined unilateral coronal synostosis have a kyphotic cranial base. Class I has more significant nasopharyngeal airway compromise in a vertical direction, whereas classes II and III have more limited oropharyngeal space.