Surgical management of cervical spine manifestations of neurofibromatosis Type 1: long-term clinical and radiological follow-up in 22 cases

Object Patients with neurofibromatosis Type 1 (NF-1) at the cervical spine present significant surgical challenges due to neural compression, multiplicity of tumors, and complex spinal deformities. Iatrogenic instability following resection of tumors is underappreciated in the literature. The focus of this study was to understand the indications for stabilization in this specific group of patients. Methods The authors performed a retrospective review of 20 cases involving NF-1 patients with symptomatic cervical spine neurofibromas who underwent surgical decompression and tumor resection, with or without instrumentation, between 1991 and 2008. They also included 2 additional cases involving patients treated before 1991. Imaging findings and data pertaining to clinical presentation, intraoperative management, and postoperative assessment were compiled to clarify the indications for stabilization. An ordinal pain scale based on patient self-assessment was used. Neurological function was evaluated using American Spinal Injury Association Impairment Scale scores. Results The patient group comprised 13 men and 9 women. Their median age at presentation was 42.5 years; their median age at initial diagnosis of NF-1 was 30 years (range 8–74 years). The median duration of follow-up (since presentation) was 7 years (range 1–32 years). Progressive myelopathy was the main presenting symptom. Spinal cord compression was identified in 13 patients on presentation. Complete removal of the symptomatic tumors was performed in 11 patients. Ten patients underwent instrumented fusion during their first surgery. Six of these 10 required a second surgery—with fixation in 4 cases and without in 2. Of the 12 patients who did not receive instrumented fusion in their first surgery, 8 required a second surgery—with fixation in 5 cases and without in 3. Neurological deterioration due to progressive deformity was the indication for the second surgery in 3 of the 5 patients who required instrumented fusion only in their second surgery; the other 2 patients presented with neurological deterioration secondary to tumor progression. Four patients needed a third operation and instrumented fusion: 3 for deformity-related deficit and 1 for tumor progression. Based on the latest follow-up, 21 patients were stable clinically and radiologically, and 1 patient had died. Conclusions This specific group of patients represents a significant surgical challenge. In this retrospective analysis, emphasis is placed on early stabilization of the cervical spine to prevent late deformity as part of the comprehensive management of patients with NF-1.

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LG-11ENDOCRINE LONG TERM FOLLOW-UP OF CHILDREN WITH NEUROFIBROMATOSIS TYPE 1(NF1) AND PPTIC PATHWAY GLIOMA (OPG)

Neuro-Oncology ◽

10.1093/neuonc/now075.11 ◽

2016 ◽

Vol 18 (suppl 3) ◽

pp. iii80.4-iii81

Author(s):

Ilaria Sani ◽

Assunta Albanese

Keyword(s):

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Long Term Follow Up

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Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01796-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

C. Ejerskov ◽

M. Raundahl ◽

P. A. Gregersen ◽

M. M. Handrup

Keyword(s):

Cognitive Impairment ◽

Learning Disability ◽

Diagnostic Criteria ◽

Clinical Features ◽

Neurofibromatosis Type 1 ◽

Plexiform Neurofibroma ◽

Neurofibromatosis Type ◽

Language Delay

Abstract Background The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications. Method A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed. Results We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. Conclusion Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

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Follow-Up of Optic Pathway Gliomas in Children with Neurofibromatosis Type 1

Neuropediatrics ◽

10.1055/s-2008-1073043 ◽

1994 ◽

Vol 25 (06) ◽

pp. 295-300 ◽

Cited By ~ 34

Author(s):

Ch. Kuenzle ◽

M. Weissert ◽

E. Roulet ◽

H. Bode ◽

S. Schefer ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Optic Pathway ◽

Optic Pathway Gliomas

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Characteristics, Treatment Patterns, Healthcare Resource Use, and Costs among Pediatric Patients Diagnosed with Neurofibromatosis Type 1 and Plexiform Neurofibromas: A Retrospective Database Analysis of a Medicaid Population

10.21203/rs.3.rs-98302/v1 ◽

2020 ◽

Author(s):

Xiaoqin Yang ◽

Kaushal Desai ◽

Neha Agrawal ◽

Kirti Mirchandani ◽

Sagnik Chatterjee ◽

...

Keyword(s):

Resource Use ◽

Neurofibromatosis Type 1 ◽

Pediatric Patients ◽

Healthcare Resource ◽

Neurofibromatosis Type ◽

Treatment Patterns ◽

Healthcare Resource Use ◽

The Mean

Abstract Background: Neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN) can cause substantial morbidity by disfigurement and compression of vital structures. Real-world data on the burden and cost of disease among pediatric patients with NF1 and PN is limited. The objectives of this study were to describe the characteristics, treatment patterns, healthcare resource use (HCRU), and costs of these patients.Results: A total of 383 patients were included in the retrospective analysis of patients aged ≤18 with at least 1 ICD-10-CM diagnosis code for both NF1 and PN enrolled in the MarketScan® Multistate Medicaid database from October 1, 2014 to December 31, 2017. The mean follow-up was 448 days. The mean age was 11.4 years and 52.0% of patients were male. Most patients were diagnosed by a specialist (63.5%). During the follow-up period, pain medications were used by 58.5% of patients, 25.1% were treated with chemotherapy, 7.1% received surgery for PN, 1.6% received MEK inhibitors, and 0.8% received radiation. Mean per patient per year inpatient, outpatient, emergency room, pharmacy, and other visits were 1.4, 17.3, 1.6, 13.6, and 25.8, respectively. Mean ±SD (median) total per patient per year healthcare costs (2018 USD) were $17,275 ±$61,903 ($2,889), with total medical costs of $14,628 ±$56,203 ($2,334) and pharmacy costs of $2,646 ±$13,303 ($26). Inpatient costs were the largest drivers of medical cost, with a mean per patient per year cost of $6,739.Conclusions: This study showed that many pediatric patients diagnosed with NF1 and PN were treated with supportive care only, highlighting a substantial unmet medical need. This study also highlights the considerable economic burden among patients with NF1 and PN.

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Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review

10.21203/rs.3.rs-96774/v2 ◽

2021 ◽

Author(s):

Cecilie Ejerskov ◽

Maj Raundahl ◽

Pernille Axel Gregersen ◽

Mette Møller Handrup

Keyword(s):

Cognitive Impairment ◽

Learning Disability ◽

Diagnostic Criteria ◽

Clinical Features ◽

Neurofibromatosis Type 1 ◽

Plexiform Neurofibroma ◽

Neurofibromatosis Type ◽

Language Delay

Abstract BackgroundThe mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications.MethodA systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed.ResultsWe identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. ConclusionPatients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

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NIMG-66. LONG-TERM FOLLOW-UP OF NEUROFIBROMATOSIS TYPE 1 PATIENTS USING WHOLE-BODY MRI DEMONSTRATES DYNAMIC CHANGES IN INTERNAL NEUROFIBROMA SIZE

Neuro-Oncology ◽

10.1093/neuonc/noz175.735 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi176-vi176

Author(s):

Ina Ly ◽

Raquel Thalheimer ◽

Wenli Cai ◽

Miriam Bredella ◽

Vanessa Merker ◽

...

Keyword(s):

Tumor Growth ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Whole Body ◽

Childhood And Adolescence ◽

Entire Study ◽

Whole Body Mri

Abstract BACKGROUND Neurofibromas affect 40–50% of neurofibromatosis type 1 (NF1) patients and can cause significant morbidity and mortality. They grow more rapidly during childhood and adolescence but studies in adults are limited by their retrospective nature and follow-up time < 3 years. The long-term natural history of neurofibromas remains unknown. No guidelines exist on the need and frequency of surveillance imaging for patients. Whole-body MRI (WBMRI) can detect whole-body tumor burden, including internal neurofibromas. METHODS 17 adult NF1 patients who underwent WBMRI between 2007–2010 (Scan 1) underwent repeat WBMRI between 2018–2019 (Scan 2). Internal neurofibromas were segmented on short tau inversion recovery (STIR) sequences and tumor volume was calculated using a computerized volumetry and three-dimensional segmentation software. Circumscribed tumors were defined as discrete; invasive tumors or those involving multiple nerves were defined as plexiform. Tumor growth and shrinkage were defined as volume change ≥ 20% over the entire study period. RESULTS Median patient age was 43 years during Scan 1 and 53 years during Scan 2. Median time between Scan 1 and 2 was 9 years. A total of 140 neurofibromas were assessed. 24% of tumors grew by a median 63% (6.8% per year). 54% of tumors spontaneously decreased in volume by a median 60% (7% per year) without treatment. On a per-patient basis, 18% of patients had overall tumor growth and 41% overall tumor shrinkage. 8 new tumors developed in 7 patients. 16 tumors resolved entirely without medical or surgical intervention. Growth behavior did not correlate with discrete or plexiform morphology. CONCLUSION A subset of internal neurofibromas in adult NF1 patients grow significantly over a long-term period, suggesting that continued monitoring of these patients may be warranted. Surprisingly, more than half of neurofibromas shrink spontaneously without intervention. Continued patient enrollment and correlation of imaging findings with functional outcomes are underway.

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Spondyloptosis of the Cervical Spine in a Patient with Neurofibromatosis Type 1

JBJS Case Connector ◽

10.2106/jbjs.cc.l.00135 ◽

2013 ◽

Vol 3 (1) ◽

pp. e5 ◽

Cited By ~ 1

Author(s):

Senthil T. Nathan ◽

Francesco T. Mangano ◽

Alvin H. Crawford

Keyword(s):

Cervical Spine ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type

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Mosaic Neurofibromatosis Type 1 in Children: A Single-Institution Experience

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475417708163 ◽

2017 ◽

Vol 21 (5) ◽

pp. 379-382 ◽

Cited By ~ 2

Author(s):

Irene Lara-Corrales ◽

Mitra Moazzami ◽

Maria Teresa García-Romero ◽

Elena Pope ◽

Patricia Parkin ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Cross Sectional Study ◽

Clinical Findings ◽

Loss Of Function ◽

Cross Sectional ◽

Uncommon Presentation ◽

Sick Children

Background: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by loss-of-function mutation in the NF1 gene. Segmental or mosaic NF1 (MNF) is an uncommon presentation of the NF1 result of postzygotic mutations that present with subtle localised clinical findings. Objectives: Our study’s objectives were to describe the clinical characteristics of children with MNF. Methods: We conducted a cross-sectional study of children diagnosed with MNF at the Hospital for Sick Children in Toronto, Canada, from January 1992 to September 2012. Data were abstracted from health records and analysed using a standardised data collection form approved by our hospital Research Ethics Board. Results: We identified 60 patients with MNF; 32 of 60 (53.3%) were female. Mean ± SD age at first assessment was 10.6 ± 4.6 years. The most common initial physical manifestation in 39 of 60 (65.0%) patients was localised pigmentary changes only, followed by plexiform neurofibromas only in 10 of 60 (16.7%) and neurofibromas only in 9 of 60 (15.0%). Unilateral findings were seen in 46 of 60 (76.7%) patients. Most common associations identified included learning disabilities (7/60; 12%) and bony abnormalities (6/60; 10.0%). Conclusions: MNF is an underrecognised condition with potential implications for patients. Children mostly present with pigmentary anomalies only. Most patients do not develop associated findings or complications before adulthood, but long-term follow-up will help determine outcomes and possible associations. Recognition and confirmation of the diagnosis is important to provide follow-up and genetic counselling to patients.

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