Cotrel-Dubousset instrumentation in neurofibromatosis spinal problems

Cotrel-Dubousset (CD) instrumentation has been employed in 12 patients with neurofibromatosis with spinal deformity (ten regular scoliosis, one dysplastic kyphoscoliosis, and one multilevel laminectomy). The follow-up period averaged 33 months. In regular scoliosis frontal correction averaged 69%, axial derotation averaged 33%, and sagittal normalcy was produced without immobilization and without pseudoarthrosis. Successful arthrodesis was obtained in a dysplastic patient after initial failure via anterior concave struts and posterior CD instrumentation with immobilization. Stabilization and fusion of one patient with multiple-level thoracic laminectomy was achieved without immobilization. CD instrumentation is effective in the surgical management of neurofibromatous spinal abnormalities.     

Evaluation of gastrointestinal hemorrhage in patients with neurofibromatosis

Over a 3-year period, two patients with neurofibromatosis were referred to our medical center for evaluation of repeated episodes of melena. Upper endoscopy was unrevealing in each case, as was colonoscopy. Arteriography during active hemorrhage was helpful in localizing the source of bleeding in one patient but not in the other. The source of bleeding in each patient was obvious at surgical exploration. Large neurofibromas protruded from the seorsal surface of a short region of jejunum in both cases and an additional segment of ileum in one case. Hemorrhage had occurred as a result of erosion of mucosa stretched over these tumors. Local resection of the involved segments produced long-term control of the hemorrhage. Since these tumors were grossly visible on the serosal surface of the involved intestinal segments, laparoscopic evaluation could have been used to hasten diagnosis in each case.     

Management of multiple tumors in neurofibromatosis type 2 patients

Introduction

Neurofibromatosis type 2 is characterized by the presence of bilateral vestibular schwannomas. However, other nervous system tumors may also occur. Therefore, the management of NF2 patients is complex and requires a multidisciplinary discussion in a specialized center.

Intraspinal rib penetration in four patients in neurofibromatosis vertebral deformities

We describe the clinical and radiological features observed in four patients with neurofibromatosis-related scoliosis or kyphoscoliosis who developed rib penetration into the intervertebral foraminae. Rib penetration should be searched for on standard and elective x-rays in patients with moderate curvatures. The diagnosis can be confirmed by computed tomography or magnetic resonance imaging of the spine. In case of major deviation, x-rays must be carefully examined, with an accurate search for spinal cord compression to avoid missing the diagnosis. Surgical treatment must consist in ablation of the posterior ends of the dislocated ribs associated with anterior and posterior fusion. It should be performed early to avoid the development of spinal cord compression.     

Decreased bone mineral density in patients with neurofibromatosis 1

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases. Although there is a considerable variability in clinical expression, NF1 is almost fully penetrant in adult patients and may be associated with a variety of skeletal anomalies. Spinal deformities are the most common skeletal manifestation, with an incidence estimated from 10–25% in various studies. Some NF1 patients have a dystrophic form of scoliosis, which is characterized by early age at onset and rapid progression. Complications have been reported during spinal instrumentation of dystrophic curves due to soft, non-resistant vertebral bony tissue, suggesting that an alteration of bone quality may occur in NF1 patients. Recent studies have suggested that decreased bone mineral density (BMD) may occur among patients with NF1. We performed a cross-sectional study on 104 adults with NF1, using quantitative ultrasonometry (QUS) to investigate whether decreased BMD is a general phenomenon in NF1 patients. The data reveal that BMD, as measured by age- and gender- adjusted Z-scores, is significantly lower in NF1 patients than in the normal reference population. The decrease in BMD appears to be even more marked among NF1 patients with scoliosis that requires surgical treatment. The findings indicate that NF1 produces a generalized alteration of bone in addition to the focal osseous dysplasias of the vertebrae, tibia, and sphenoid wing that characterize this condition. The pathological mechanism underlying these bony changes remains to be elucidated.     

Modulation of spinal deformities in patients with neurofibromatosis type 1

STUDY DESIGN: A consecutive case retrospective chart and radiographic review. OBJECTIVES: To determine the incidence of nine radiographic dystrophic features acquired during the process of modulation, and to analyze the statistical correlation of these acquired dystrophic features with clinical progression of a spinal deformity. SUMMARY OF BACKGROUND DATA: In patients with neurofibromatosis, spinal deformities with seemingly few initial dystrophic features have shown a tendency to acquire dystrophic changes during long-term follow-up periods. Similarly, deformities with dystrophic changes can acquire further dystrophic features. This phenomenon is termed "modulation," a feature unique to spinal deformities in neurofibromatosis. These dystrophic changes may evolve slowly or aggressively, and may spread to other regions as well. METHODS: A review was done of the clinical records, photographs, radiographs, and other imaging studies of 457 patients referred between 1982 and 1995 with the diagnosis of neurofibromatosis Type 1. One hundred twenty-eight patients were diagnosed with a spinal deformity. Ninety-one patients who had a complete set of clinical and radiographic data were included in the study. Location and type of curve as well as the extent of spinal deformity were studied for their effect on the tendency for modulation. Initial spinal radiographs were analyzed for nine radiographic dystrophic features: rib penciling, vertebral rotation, posterior vertebral scalloping, anterior vertebral scalloping, lateral vertebral scalloping, vertebral wedging, spindling of the transverse process, widened interpedicular distance, and enlarged intervertebral foramina. Subsequent radiographs were analyzed critically for evolution, progression, or spread of these features. Correlation of acquisition in these dystrophic features with clinical progression in the spinal deformity, as measured in increments of scoliosis and kyphosis, was analyzed. RESULTS: In 81% of patients with spinal deformity diagnosed before 7 years of age and in 25% of patients with such a diagnosis after 7 years of age, evidence of modulation was observed. Location, side, and extent of the deformity and patient gender did not influence the propensity of the deformity to modulate. Correlation of modulation with clinical progression of the deformity showed rib penciling to be the only singular factor statistically influencing risk of progression. Of the deformities that acquired three or more penciled ribs, 87% showed significant clinical progression. No other radiographic dystrophic feature individually influenced progression. However, when three or more of the dystrophic skeletal features were acquired, the risk of progression reached statistical significance in 85% of patients. CONCLUSIONS: Spinal deformities in patients with neurofibromatosis 1 should be regarded as deformities in evolution. One should resist assigning these evolving deformities to either the dystrophic or nondystrophic end of the spectrum without considering the possibility of modulation across the spectrum. A spinal deformity that develops before 7 years of age should be followed closely for evolving dystrophic features (i.e., modulation). When a curve acquires either three penciled ribs or a combination of three dystrophic features, clinical progression is almost a certainty.     

Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2

OBJECT: The results of two longitudinal studies of growth rates of vestibular schwannomas (VSs) in patients with neurofibromatosis Type 2 (NF2) differ as to whether VS growth rates decrease or increase with increasing patient age. The authors undertook this study to assess the relationship between VS growth rates and patient age and type of constitutional NF2 mutation; they also examined variability in VS growth rates among multiple patients in families with NF2. METHODS: Gadolinium-enhanced magnetic resonance images obtained in 18 patients with inherited NF2 from 11 unrelated families were retrospectively analyzed. The patients had been observed for a median of 4 years. Volumes of the VSs were measured using a two-component box model (intrameatal and extrameatal parts measured separately). Single-strand conformation polymorphism analysis and Southern blot analysis were used to identify constitutional NF2 mutations. Growth rates of the VSs were highly variable, but tended to decrease with increasing patient age both at onset of signs or symptoms of NF2 (r2 = 0.35, p = 0.026) and at diagnosis (r2 = 0.33, p = 0.012). The VS growth rates did not vary significantly with the type of constitutional NF2 mutation or the number of non-VS cerebral or spinal tumors. The VS growth rates were highly variable within families and did not correspond to clinical indices of NF2 disease severity, such as patient age at symptom onset and the number of non-VS cerebral and spinal tumors. CONCLUSIONS: The growth rates of VSs in patients with NF2 are highly variable, but tend to decrease with increasing patient age. Clinical treatment of multiple patients in families with NF2 cannot be based on the expectations of similar VS growth rates, even when other clinical aspects of disease severity are similar.     

Prognostic value and management of spinal tumors in neurofibromatosis type 2 patients

Purpose

Neurofibromatosis type 2 (NF2) is a well-studied disease. Although spinal tumors are frequent, many issues concerning their prognosis and management still have to be clarified. The authors studied the clinical impact and radiological progression of spinal tumors in patients with NF2 to determine their prognostic value.

Methods

A total of 80 NF2 patients were followed in the Lille University Hospital between 1987 and 2011. Clinical, radiological and genetic data were retrospectively recorded and analyzed. Patients underwent annual cranial and spinal MRI. Both the location and size of each tumor were reported. The diagnosis of NF2 was confirmed either because the patient met the Manchester criteria or by the presence of genetic mutation.

Results

The mean follow-up period was 8.8 years (range 1 to 24 years; SD: ±0.8), and the mean age at diagnosis was 27.2 years (range 6 to 73 years; SD: ±1.7). Among all patients, 48 harbored spinal tumors. Twenty of them were symptomatic, and 21 were operated on. Patients with spinal tumors had a lower age at diagnosis (p?=?0.02), a higher number of intracranial meningiomas (p?=?0.028) and schwannomas (p?=?0.03), and more nonsense and frameshift mutations (p?=?0.04).

Conclusion

Spinal tumors are common in NF2, and all patients should be regularly monitored by spinal MRI. The presence of spinal tumors seems to be a factor indicating poor prognosis. Clinical and radiological monitoring of spinal tumors could lead to early treatment both when clinical symptoms are present and in case of proven radiological evolution, maintaining a favorable functional prognosis as long as possible.     

Genitourinary neurofibromatosis in childhood

Neurofibromatosis in children occurs uncommonly and involvement of the bladder is exceedingly rare. The syndrome is transmitted as an autosomal dominant trait and is characterized by cutaneous pigmentation and tumors of neural crest origin. Hypertension has been documented in association with neurofibromatosis in the form of renovascular disease in children and with pheochromocytomas in adults. We report on 2 children with extensive neurofibromas of the bladder, upper tract damage and genital enlargement. One case was misdiagnosed as posterior urethral valves and the other case as clitoral hypertrophy. The literature of urogenital neurofibromatosis is reviewed with particular attention to bladder lesions, hypertension, malignant potential and treatment options.     

Orbital neurofibromatosis

The origin of neurofibromatosis (the neuroectoderm, the mesectoderm, or both primordia?) is not known. The protean manifestations of the disease cannot be explained, and classification of the various forms of orbital neurofibromatosis on the basis of specific neural involvement has never been attempted. Further studies of the pathogenesis are therefore urgently needed. Differentiation between types of orbital tumors may benefit from advanced computer scanning and nuclear magnetic resonance techniques. The results of surgical treatment, although much improved in recent years, are still unsatisfactory. Concentration of patients with neurofibromatosis in specialized centers is therefore indicated.     

Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study

Nine duodenal carcinoids from patients with von Recklinghausen's neurofibromatosis (VRNF) were investigated for their morphologic, immunocytochemical, and ultrastructural characteristics, and were compared with seven similar tumors from patients without VRNF. Strong similarities were found between tumors in each group. Irrespective of their association with VRNF, duodenal carcinoids arose in adults and usually produced jaundice, upper intestinal bleeding, or obstruction. Tumors larger than 2.0 cm had already metastasized when first detected. All tumors showed a mixed architectural pattern; five tumors associated with VRNF were of the psammomatous type, as opposed to two of those without VRNF. While no tumors showed argentaffinity, stray argyrophil cells were present only in the three tumors not associated with VRNF. All of the tumors showed immunocytochemical evidence of somatostatinomas, and only one VRNF-associated tumor showed immunoreactivity for an additional regulatory substance, as opposed to three of those not associated with VRNF. Thus, while VRNF-associated duodenal carcinoids are not otherwise distinctive, they tend to be pure somatostatinomas (eight of nine cases), whereas similar tumors unassociated with VRNF are frequently multihormonal (three of seven cases). While many more duodenal carcinoids need to be investigated systematically for their immunocytochemical profile, detection of a pure somatostatinoma in the duodenum should alert one to the possibility of coexistent VRNF.     

Benign brain stem lesions in pediatric patients with neurofibromatosis: case reports

The symptoms and clinical courses of 4 patients with neurofibromatosis and lesions of the brain stem identifiable on computed tomographic and/or magnetic resonance imaging scans are described. Two patients underwent biopsy and both had low-grade astrocytomas with no evidence of anaplasia. Both received radiation and chemotherapy. The other 2 patients have been monitored without biopsy or treatment. Three patients are alive and clinically stable, having been followed up for an average of 4 years; neuroimaging studies have shown no change in their tumors. The fourth patient died of a supratentorial primitive neuroectodermal tumor. Imaging studies had shown no change in his brain stem lesion, which at autopsy was found to be a focal collection of fibrillary astrocytes. These data suggest that some patients with brain stem lesions and neurofibromatosis may have a prognosis distinctly different from that of the typical patient with a brain stem glioma. We recommend caution against aggressive operative and adjuvant therapy for brain stem lesions in patients with neurofibromatosis, unless progression of the lesion is documented clinically and/or by imaging.     

Scoliosis surgery in neurofibromatosis

Twenty-three patients who were treated by posterior spinal fusion with neurofibromatous scoliosis were reviewed to study the adequacy of spinal fusion, rate of pseudarthrosis, and incidence of complications. Twenty patients achieved a solid fusion with posterior surgery alone. Thirteen patients required one or more posterior augmentation procedures because of progressive deformity. Three patients with dystrophic kyphoscoliosis required an anterior spinal fusion in addition to the posterior fusion to achieve a solid fusion mass. The type of graft material, Harrington instrumentation, and degree of kyphosis or scoliosis had no effect on the rate of pseudarthrosis. Preoperative neuroradiographic evaluation was found to be warranted for all patients with neurofibromatous scoliosis.