Neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a common inherited complex multi-system disorder associated with the growth of various benign and malignant tumors, being Pilocytic Astrocytomas (PA) a common benign central nervous system (CNS) tumour occurring in this setting. Although this is a common association, simultaneous development of multiple lesions is an infrequent finding, especially in non-optic or hypothalamic locations 1).

Neurofibromatosis 1 occurs with approximately 1 : 2000 to 1 : 5000 in individuals.

About 40% of Neurofibromatosis type 1 patients develop spinal tumors, of whom some have familial spinal neurofibromatosis (FSNF), a variant form of NF1 in which patients present with multiple bilateral spinal tumors but have few other clinical features of the disease 2).

The diagnosis of most NF1 patients is based on clinical manifestations.

Cognitive dysfunction accompanied by neurofibromatosis type 1 is one of the significant characteristics of this neurocutaneous disorder and has a serious impact on patients' quality of life. Although studies on cognitive function in children with neurofibromatosis type 1 have revealed that attentional impairment is a key deficit in these patients, few studies have examined their neuropsychological profile, especially whether the attentional function is also abnormal and specific in adult patients with neurofibromatosis type 1. In this study, we used the revised attention network test to examine the function of three attentional networks-alerting, orienting and executive control-in 20 adult patients with neurofibromatosis type 1 in comparison to 20 normal controls. Adult patients with neurofibromatosis type 1 showed significant greater conflict effect for the executive control network, but no significant differences were found for alerting and orienting network relative to normal controls. These results provide evidence that there is an attentional deficit which is specifically associated with the executive control network in adult patients with neurofibromatosis type 1 3).

Requires at least two major criteria below : 2 or more neurofibromas or 1 plexiform neurofibroma, 6 or more café-au-lait patches, axillary or groin freckling, optic pathway glioma, lisch nodules in the Iris, a distinctive osseous lesion, a first degree relative with NF1.

Spinal tumors occur in approximately 40% of patients with NF1.

see Hypothalamic glioma.

see Neurofibromatosis type 1 related hydrocephalus.

Vaassen et al., reported an 11-year-old Neurofibromatosis type 1 patient with a large plexiform neurofibroma of the neck that had led to a sharp-angled kinking of the cervical spine and subsequent myelopathy. Although surgical stabilization of the cervical vertebral column was urgently recommended, the vertebral column was inaccessible due to extensive tumor growth. In this situation, treatment with the MEK inhibitor trametinib was initiated which resulted in a 22% reduction in tumor volume after 6 months of therapy and finally enabled surgery. These data show that MEK inhibitors may not lead to complete disappearance of NF1-associated plexiform neurofibromas but can be an essential step in a multimodal therapeutic approach for these tumors. The course of this patient suggests that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1 4).

A 41 year-old female patient with neurofibromatosis type 1 and uncontrolled human immunodeficiency virus (HIV) type 1 infection presents with a first generalized seizure and associated headache and ataxia. Imaging studies revealed two large intra-axial tumours, nodular-cystic in the supratentorial compartment and solid in the infratentorial compartment. Both lesions were gross-totally removed in two surgeries performed with an interval of one-week. Despite their different imaging patterns, they were histologically and genetically identical.

Forte et al., present a unique case of two histologically and genetically identical pilocytic astrocytomas occurring simultaneously in supratentorial and infratentorial locations. They suggest that intrinsic tumour development predisposition associated to NF1 might have been enhanced by HIV-related immunosuppression in this case. Strict oncological surveillance is essential in patients with tumour predisposition syndromes combined with immunosuppression 5).

1) , 5)
Forte D, Nabais A, Pontinha C, Mafra M, Mateus L. Simultaneous supratentorial and infratentorial pilocytic astrocytoma in an adult patient with concurrent neurofibromatosis type 1 and HIV infection. World Neurosurg. 2018 Jun 13. pii: S1878-8750(18)31225-7. doi: 10.1016/j.wneu.2018.06.011. [Epub ahead of print] PubMed PMID: 29908379.
Upadhyaya M, Spurlock G, Kluwe L, Chuzhanova N, Bennett E, Thomas N, Guha A, Mautner V. The spectrum of somatic and germline NF1 mutations in NF1 patients with spinal neurofibromas. Neurogenetics. 2009 Jul;10(3):251-63. doi: 10.1007/s10048-009-0178-0. Epub 2009 Feb 17. PubMed PMID: 19221814.
Wang X, Wu Q, Tang H, Zhao F, Yang Z, Wang B, Li P, Wang Z, Wu Y, Fan J, Liu P. Selective impairment of the executive attentional network in adult patients with neurofibromatosis type 1. Neuroreport. 2019 Aug 14. doi: 10.1097/WNR.0000000000001275. [Epub ahead of print] PubMed PMID: 31425345.
Vaassen P, Dürr N, Röhrig A, Willing R, Rosenbaum T. Trametinib Induces Neurofibroma Shrinkage and Enables Surgery. Neuropediatrics. 2019 May 29. doi: 10.1055/s-0039-1691830. [Epub ahead of print] PubMed PMID: 31141829.
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  • Last modified: 2019/08/21 08:32
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