Complication Of Neurofibromatosis Type Research Articles

Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

BackgroundCognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? MethodsWe used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. FindingsNF1 patients experienced substantial decline in motor skill acquisition (F=9.2, p=0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T=2.8, p=0.014), especially evident after the early acquisition phase. InterpretationsCollectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

Treatment of Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a genetic multisystemic disorder involving the skin, the central and peripheral nervous systems, bones, and the cardiovascular and endocrine systems. This condition is caused by inherited or de novo mutations of the NF1 gene at the 17q11.2 chromosomal region, a gene that codes for the protein neurofibromin. Neurofibromin is particularly expressed in neural cells and inhibits the RAS pathway, which regulates cellular proliferation and differentiation. The typically age-dependent emergence of diagnostic signs and the risk for severe complications in the first years of life simultaneously makes a precocious diagnosis crucial and makes the management of children with suspected NF1 challenging. Currently, no standardized specific treatments for NF1 and its complications are available. However, in recent years, increasing knowledge of the pathogenetic mechanisms has motivated the scientific search behind targeted biological agents that might change the course of the disease. Numerous clinical trials for the treatment of the most typical NF1 complications, such as plexiform neurofibromas (Ns) and NF1-related tumors, have been conducted. Consequently, encouraging in vitro and in vivo results are emerging. Insufficient efficacy and safety in in vivo data do notpermit the routine use of these drugs in clinical practice. Radiotherapy appears to be indicated only for high-grade soft-tissue sarcomas, whereas surgical approaches should be considered for malignant peripheral nerve sheath tumors (MPNSTs) and Ns, optic pathway gliomas, and bone dystrophic changes because they might improve quality of life. Further prospective studies, however, are needed to confirm the efficacy, safety, and cost/benefit ratio of new therapeutic approaches and the optimal timing for their use in patients with NF1.

The Impact of Neurofibromatosis Type 1 on the Health and Wellbeing of Australian Adults.

The complications of neurofibromatosis type 1 (NF1) are widespread, unpredictable and variable and each person's experience of this disorder is unique. However, few studies have addressed the impact of NF1 from an individual's perspective. This qualitative study aims to identify the ways in which NF1 impacts upon affected Australian adults. Sixty adults with NF1, with a range of disease severity and visibility participated in a semi-structured interview about the ways in which NF1 impacted upon their life and health. Data were analyzed using grounded theory methodology. Results indicated that NF1 impacts upon affected adults in five major ways: 1) cosmetic burden of disease 2) learning difficulties 3) concerns about the risk of passing NF1 to offspring 4) uncertain disease progression, and 5) pain. Participants identified the aspects of NF1 that bothered them the most, creating a hierarchy of NF1 concerns within the cohort. Importantly, mildly affected adults shared many of the same concerns as those more severely affected. This study enhances our current understanding of the impact of NF1 in adulthood, and augments existing recommendations for the care of these patients.

Multidimensional Ultrasound and Computed Tomography Imaging Support in Bleeding Plexiform Neurofibromatosis of the Scalp: A Case Report and Literature Review.

Active bleeding in plexiform neurofibromatosis can be a life-threatening complication in neurofibromatosis type 1 (NF1). The prompt imaging support of 2D-3D ultrasound (US) and computed tomography (CT) during the active hemorrhage phase of cutaneous neurofibromas has not been previously reported. We report a case with NF1 who experienced a sudden swelling in the parieto-temporal region that corresponded to a massive and active hemorrhage within a plexiform neurofibroma. The US and CT imaging characteristics of this bleeding tumor are shown. Active hemorrhage in a plexiform neurofibroma of the scalp appeared in US as a heterogeneous hypodermal mass. CT demonstrated a fully hyperdense soft tissue mass. These characteristics differ from the non-complicated or old hemorrhagic imaging appearances of scalp plexiform neurofibromas and encourage prompt surgical treatment. This case report demonstrates the usefulness of imaging support in the early diagnosis of this hemorrhagic complication of NF1 in the scalp and also stimulates multispecialty management.

Intima-Type Vasculopathy in Neurofibromatosis Type 1

Introduction: Neurofibromatosis type 1 is an autosomal-recessive, monogenetic disease (NF1 gene 17q22.1) with an incidence of 1:3,000. Clinical symptoms affect skin, eyes, central and peripheral nervous system, and bones. We report about a 10-year-old girl with intima-type vasculopathy followed by peripheral arterial occlusive disease grade 4 according to the neurofibromatosis. Case Report: At the age of 6 years, a difference in the length of legs was noticed and treated with insoles and orthopedic shoes. At the age of 9 years, consultation of an orthopedic specialist revealed genu varum and temporarily epiphysiodesis was done. After 8 months of a therapy refractory, painful soft tissue infection on one foot occurred. Despite local and systemic antimicrobial therapies a dry ulcer on the forefoot and humid necroses between the toes developed. Further diagnostic measures showed demineralization of the lower leg and tarsus as well as old fractures of the metatarsalia. Conventional angiography and angio-magnetic resonance imaging revealed an obliteration of the posterior tibial artery and high-grade stenoses of the anterior tibial artery and the fibular artery with multiple collaterals. In synopsis of the clinical and radiographic findings, a peripheral arterial occlusive disease grade 4 was diagnosed. After ineffective medicamentous and interventional attempts to improve perfusion, amputation of the lower leg was performed. Histological examination of the arterial blood vessels in the amputation stump provided evidence of changes in terms of an intima-type vasculopathy with subtotal to total stenoses due to intimal hyperplasia consistent with vascular neurofibromatosis. Conclusion: Vascular complications in neurofibromatosis type 1 are described in literature as fibromuscular dysplasia in renal arteries and as stenoses or ectasias of the carotids or the cerebral arteries. Vasculopathies of the peripheral arteries leading to the clinical picture of a peripheral arterial occlusive disease are extremely rare, especially in childhood. Differences in length or circumference of extremities, trophic dysfunction, abnormal wound healing, or persistent pain should result in further angiologic diagnostics.

Utility of 18F-FDG PET with a Semi-Quantitative Index in the Detection of Sarcomatous Transformation in Patients with Neurofibromatosis Type 1

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are a serious complications of neurofibromatosis type 1 associated with poor prognosis and deeper lesions can be difficult to diagnose. 18-FDG PET improves the detection of malignancies. However, the criteria for malignancy, notably the SUVmax threshold, are not standardized. Therefore, the aim of the study was to evaluate a semi-quantitative index for the reproducible detection of MPNST with FDG PET.MethodsIt is a multicenter retrospective study conducted between 2000 to 2012. All patients with NF1 referred for suspected MPNST underwent PET. Since SUVmax was not available until 2004 in our centers, we had to settle for the semi-quantitative method used at that time, the uptake ratio between the tumor and the normal liver (T/L ratio) with 1.5 as the cut-off for malignancy. When dedicated PET with SUVmax became available, the semi-quantitative analysis of PET images remained, along with SUVmax.Results113 patients with 145 tumors were included. PET assessment revealed 65 suspected lesions with T/L >1.5 and among these, 40 were MPNSTs. 80 tumors were classified as non-suspicious, and 79 were benign. The 1.5 T/L cut-off had a negative predictive value (NPV) of 98,8% and a positive predictive value of 61,5%. The positive likelihood ratio (LR) was 4,059, the negative LR was 0,032 with 97% sensitivity and 76% specificity.ConclusionsThis study, which is among the largest published, confirms the utility of PET for detecting NF1-associated MPNSTs. A semi-quantitative index, the T/L ratio with a cut-off of 1.5, allowed sensitive and specific differentiation of malignant from benign tumors better than SUVmax. When T/L was <1.5, MPNSTs were ruled out with 98,8% NPV. When T/L was >1.5, there was a strong suspicion of malignancy. This semi-quantitative analytical method is as simple as SUVmax, but is more sensitive, more reproducible and non-user-dependent.

Cerebrovascular stenosis in neurofibromatosis type 1 and utility of magnetic resonance angiography: our experience and literature review

Neurofibromatosis type 1 (NF1) is a multisystem autosomal dominant disorder that primarily involves the skin and the nervous system. Development of cerebral arterial stenosis is a potentially deadly complication of NF1, which is frequently underestimated. The aim of our paper is to report the frequency of this cerebrovascular disease in a series of patients affected by NF1, using magnetic resonance angiography (MRA). A review of the literature was also performed, focused on the usefulness of MRA in NF1 patients. Among 125 patients with NF1 (clinical diagnosis according to the standard National Institutes of Health criteria), 81 (65%) were studied with brain MRI (magnetic resonance imaging) and MRA using a 1.5 T magnet. Multiple intracranial arterial stenoses were found in six patients (7.4%). In our study, MRA proved to be critical, especially for the detection of stenoses in the branches of the Circle of Willis. Few case series have investigated the incidence of vascular complications of NF1, and most of them have used MRI. We suggest adding MRA to the brain imaging of all these patients, as stenoses of the branches of the Circle of Willis are often undetectable by MRI only.

Neurofibromatose tipo 1: relato de um caso clínico

Introduction: Neurofibromatosis type 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. A new mutation occurs in about half of the cases. The diagnosis is based on clinical assessment so family physicians should be aware of the manifestations of the disease. Case presentation: A 29 year-old female patient presented with a history of numerous skin lesions since childhood. The lesions were getting progressively worse. The patient also had learning disabilities. Her mother had similar skin lesions. She was referred to a General Surgery clinic in 2008 because of “multiple moles and warts”. After excision of skin lesions, a pathological diagnosis, of neurofibromas was made in 2009. She was referred to a Neurology clinic and the clinical diagnosis of NF1 was confirmed by the presence of neurofibromas, freckles, and more than 6 cafe au lait spots on the skin. It was also noted that her three year-old son had one cafe au lait patch on his skin. The child was referred to a Dermatology clinic in 2012. At this time the child fulfilled the clinical criteria for the diagnosis of NF1. Commentary: Because of the prevalence (1/2500-3000) and severity of complications of NF1, the early detection of the disease is important. As is evident in this case, clinicians are not always aware of its manifestations, missing opportunities for genetic counselling and preventing complications of the disease.

Does the Presence of Dystrophic Features in Patients With Type 1 Neurofibromatosis and Spinal Deformities Increase the Risk of Surgery?

Retrospective chart and radiographical review. To present the demographics of patients with scoliosis and neurofibromatosis type 1 (NF-1), to record the incidence of dystrophic features, and to determine whether the presence of dystrophic features increase the risk of surgery in patients with NF-1 and associated spinal pathology. The most common of the osseous complications of NF-1 is spinal deformity, occurring in 10% to 30% of individuals with NF-1. Many of these patients will eventually require surgery for curve progression, which makes study of demographics and identification of features predicting the need for surgery essential in this patient population. A retrospective review was performed in patients with NF-1 and spinal deformities, followed in a multidisciplinary neurofibromatosis center. A subset of 56 patients with complete radiographical evaluation was reviewed for identification of risk factors for spine surgery. One hundred thirty-one patients from a population of 694 patients with NF-1 (19%) had scoliosis. Mean age at diagnosis of scoliosis was 9 years (range; 1-17 yr). Scoliosis and need for surgery were equally distributed between males and females. In the group of 56 patients, 63% had 3 or more dystrophic features. The presence of 3 or more dystrophic features was the strongest predictor of the need for surgery (odds ratio = 14.34; P < 0.001). Individual features most predictive of need for surgery were the presence of vertebral scalloping (odds ratio = 13.19; P < 0.001) followed by the presence of dural ectasia (odds ratio = 6.38; P = 0.005). Patients with no dystrophic features were unlikely to progress to need for surgery. Scoliosis and need for surgery were equally distributed between males and females. The presence of 3 or more dystrophic features was highly predictive of the need for surgery, with the most significant individual predictors being vertebral scalloping and dural ectasia. A combination of radiographical and MRI features can be used to predict need for spinal surgery. 3.

Persistent Hypertension Despite Successful Dilation of a Stenotic Renal Artery in a Boy With Neurofibromatosis Type 1

Hypertension is one of the major complications in neurofibromatosis type 1 (NF1). It is known to be caused by renal artery stenosis or pheochromocytoma. However, more than half of hypertensive patients with NF1 do not have either disorder. We report here on a 13-year-old male with NF1 who had hypertension and a stenosis of the right renal artery associated with elevated renal vein renin on the diseased side. He underwent percutaneous transluminal renal angioplasty. In spite of successful dilation of the artery and normalized renin level, high blood pressure persisted beyond 6 months requiring antihypertensive medication. His wide pulse pressure suggested arterial stiffness due to NF1 vasculopathy. We posit that the cause of hypertension in this patient was considered to be arterial stiffness ascribed to NF1 vasculopathy rather than renal artery stenosis. Increased pulse pressure supports the hypothesis. This marker of arterial stiffness can be assessed non-invasively and should be evaluated routinely in NF1.

Evaluation of Tibial Osteopathy Occurrence in Neurofibromatosis Type 1 Italian Patients

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype. Patients of both groups were subdivided by gender and re-evaluated for these items. Statistical comparison was carried out between the two groups of patients for each feature. We collected data on type of treatment and on the clinical conditions of NF1-TO patients after follow-up. Patient's age at NF1 diagnosis was significantly younger in NF1-TO subjects compared with NF1 subjects without TO, and the incidence of T2H was significantly reduced in NF1-TO males compared with NF1 males without TO. The presence of TO does not imply that there is an increased risk of developing typical complications of NF1 (e.g., optic pathway glioma, plexiform neurofibroma, etc.), however, it does allow us to make an earlier diagnosis of NF1.

Melena, A Complication of Neurofibromatosis Type 1 Often Overlooked

Purpose: Neurofibromatosis Type 1 (NF1) is an autosomal dominant disease that causes many types of skin and central nervous system tumors. The gastrointestinal tract is involved in about 10-25% of presentations. Of those, less than 40% typically have gastrointestinal bleeding. We report a case of a patient with NF1 presenting with melena found to have a tumor present at the ileo-cecal valve. Methods: A 44 year-old African American female with a past medical history of NF1 and hypertension presented to her primary care physician with a complaint of six days of melena progressing to passing red blood clots. The last occurrence was two days prior to arrival. In addition, she complained of generalized fatigue and lightheadedness upon standing. Labs revealed that her hemoglobin had dropped from 12 g/dL to 6.2 g/dL over a three-month period. The patient denied any abdominal pain, nausea, vomiting, dysphagia, weight loss, or diarrhea. She stated that she had a previous episode of melena about 20 years prior. At that time, an EGD and colonoscopy were performed revealing only an “ulcer” per the patient. The patient was referred immediately to our gastroenterology clinic for esophagogastroduodenoscopy (EGD) and potential colonoscopy if no etiology of the bleed was found. The EGD was performed revealing no source of anemia or melena. As a result a colonoscopy was performed that showed a large, approximately four centimeter semi-pedunculated mass with a flat base involving about 50% of the lumen at the ileo-cecal valve (see Image 1). The lesion contained ulceration with a red spot, but without a visible vessel, clot, or active bleeding. Multiple biopsies were obtained, but were inconclusive. The patient was referred to general surgery for resection. Results: Gastrointestinal bleeding is a rare, but potentially life threatening complication of neurofibromatosis. Treatment is surgical resection - eliminating the risk of bleeding and provides opportunity for malignancy evaluation. Conclusion: Melena is a complication of neurofibromatosis that can be life threatening if overlooked. Therefore, clinicians must keep neurofibromatosis tumors involving the gastrointestinal tract as part of their differential diagnosis in patients with neurofibromatosis who present with gastrointestinal bleeding.Figure: Image 1: Mass at the ileo-cecal valve.

Subarachnoid hemorrhage in neurofibromatosis type 1: Case report of extracranial cerebral aneurysm rupture into a meningocele

Described here is a case of subarachnoid hemorrhage due to rupture of an extracranial vertebral artery (V3 segment) aneurysm in a patient with neurofibromatosis type 1 (NF-1). The pathophysiology of this never-before reported complication of NF-1 is examined in the light of a focused literature review and with illustrations characteristic of this unique case, involving complex malformations of the spine and meningeal spaces, as well as of the vertebral artery wall itself. All these abnormalities are directly related to the underlying NF-1 disease.

Hearing Improvement after Bevacizumab in Patients with Neurofibromatosis Type 2

Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors. We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline. VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2. VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.

Neurofibromatose tipo 1: mais comum e grave do que se imagina

To study prevalence of clinical features among Brazilian patients diagnosed with neurofibromatosis type 1(NF1), comparing these features with international data to evaluate the severity and visibility of the disease and quantify less frequent manifestations such as short stature, macrocephaly, muscle strength, voice abnormalities and oral motor disorders. 183 patients diagnosed with NF1, attended at the Neurofibromatosis Outpatient Reference Center, were evaluated for clinical manifestations and complications of NF1. Severity and visibility were verified using the Riccardi and Ablon scales respectively. Voice abnormalities and oral motor disorders were quantified using the Vox-Metria software and maximal voluntary muscle strength (MVMS) was quantified using a handgrip dynamometer. Clinical manifestations of NF1 observed were comparable to those described in literature. However, more then 50% of patients presented severity and visibility classified as moderate and severe. The incidence of macrocephaly and short stature was higher among the Brazilian patients. Voice abnormalities and oral motor disorders were quantified for the first time, with hoarseness and oral motor disorders observed in more then 60% the patients. Maximal voluntary muscle strength was found to be reduced in 67% of patients. The main clinical features of these patients are similar to those reported in previous studies. More then one-half of the patients presented moderate and severe levels of NF1 (severity and visibility), including short stature, macrocephaly, voice abnormalities and oral motor disorders and decreased muscle strength. These results are in disagreement with the traditional concept that NF1 is a benign disease and also disclosed some clinical aspects not previously reported.

Statins, bone, and neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a dominantly inherited multi-system disorder. Major features include pigmentary abnormalities, benign tumors of the nerve sheath (neurofibromas), malignant tumors, learning disabilities, and skeletal dysplasia. The NF1 gene functions as a tumor suppressor, but haploinsuffiency probably accounts for some aspects of the non-tumor phenotype. The protein product, neurofibromin, is a Ras GTPase-activating protein, and various Ras pathway inhibitors are being tested in preclinical models and clinical trials for effectiveness in treating NF1 complications. This month in BMC Medicine, a paper by Kolanczyk et al describes a preclinical mouse model for tibial dysplasia and provides evidence that the drug lovastatin – in use to treat cardiovascular disease – may be beneficial, opening the door to clinical trials in humans.

Parental Reports of Health-Related Quality Of Life in Young Children with Neurofibromatosis Type 1: Influence of Condition Specific Determinants

To assess the health-related quality of life of 34 Dutch children 12 to 72 months of age with neurofibromatosis type 1 (NF1) using the Infant/Toddler Quality of Life Questionnaire (ITQOL) and to investigate the potential impact of clinical factors on parental reports of health-related quality of life. A parent-completed form including the ITQOL, NF1-specific questions, and sociodemographic questions was sent. ITQOL scale scores were compared for the study population against Dutch reference values. The influence of general and clinical characteristics on ITQOL scale scores was evaluated with multivariate analysis. A significant impact was observed on most aspects of quality of life, particularly for growth and development, general health perceptions and parental impact. The lowest scores were observed in children with complications because of NF1. ITQOL scale scores were affected by parental educational level, familial NF1, and parental reports of complications of NF1 and perceived disease severity. Important aspects of health-related quality of life were observed to be negatively affected in children with NF1, as measured by the ITQOL. Family-related and disease-related variables appeared to influence the quality of life in children with NF1.

Type 1 neurofibromatosis complicated by pulmonary artery hypertension: a case report

We describe the case of a patient with neurofibromatosis type 1 (NF1) complicated by severe pulmonary aterial hypertension (PAH); only seven cases have been reported on this association so far, and PAH seems to be related to the vascular involvement of neurofibromatosis. The histology of our patient's lung tissue showed thickening of arteries and veins by medial and/or intimal hypertrophy and fibrosis. In order to exclude a familiar PAH, the analysis of the bone morphogenetic protein receptor 2 gene was carried out, but no mutations were found. On the basis of histological findings and of the results of genetic study we believe that PAH was a complication of NF1 in our patient and we suggest to screen patients with NF1 for the presence of PAH by means of trans-thoracic echocardiogram.

Neurofibromatosis type 1: New insights into neurocognitive issues

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder with a prevalence of approximately 1 in 3500 people. Academic difficulties and school failure are the most common reported complication of NF1 in childhood and are present in 40% to 60% of the cases. They are often the most significant cause of lifetime morbidity in this population. Recent advances in the recognition and characterization of the cognitive phenotype in NF1 patients have provided a better understanding of the neuropsychologic deficits that account for the impairments in cognitive performance and social interaction. Additionally, recent advances in the understanding of molecular and cellular mechanisms underlying the cognitive deficits in NF1, as well as developments in neuroimaging and molecular genetic techniques are starting to yield a global and integrative picture of the molecular, cellular, and brain system processes affected by this condition. This review focuses on these advances, as well as recent preclinical studies that point towards potential pharmacologic interventions for NF1 patients.

Malignant peripheral nerve sheath tumour of the cervical vagus nerve in a neurofibromatosis type 1 patient

One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear.