Central Neurofibromatosis Research Articles

Screening saves sight: An unusual case of type-1 neurofibromatosis

Neurofibromatosis (NF), described by von Recklinghausen in 1882, consists of at least two distinct disorders: NF1 (von Recklinghausen's or peripheral neurofibromatosis) and NF2, formerly known as 'central neurofibromatosis." The prevalence of NF is approximately 1 in 4,000, and of NF2, 1 in 50,000. Neurofibromatosis type 1 is a multisystemic neurocutaneous disorder with an autosomal dominant hereditary pattern. Ocular manifestations include plexiform neurofibroma of eyelid, Lisch nodules in iris, optic nerve glioma, glaucoma, sphenoid wing dysplasia. Retinal and choroidal involvement are encountered less frequently. Unusual ocular findings include multiple choroidal nevi, combined hamartoma, choroidal Schwannoma, choroidal melanoma and vaso proliferative retinal tumors.Here we report a case of an 18 year old girl diagnosed with neurofibromatosis type 1 who on routine ocular examination was found to have high myopia in both eyes and on fundus examination had a macula ‘on’ inferior retinal detachment with retinal hole in right eye. Inferior retinal detachment is rarely reported in neurofibromatosis type 1. This case emphasizes the importance of conducting ocular examination even in asymptomatic patients with neurofibromatosis, so that early detection and treatment can prevent vision loss secondary to retinal detachment.

A patient with features of both Neurofibromatosis I and Neurofibromatosis II on MR imaging

Neurofibromatosis (NF) type II is a neurocutaneous disease with an autosomal dominant pattern of inheritance with its gene locus on chromosome 22q 12 with bilateral acoustic schwannoma being the hallmark of this disease. NF II is considered central neurofibromatosis while NF I is the peripheral neurofibromatosis. This case report presents a case of a 15 year old female who came with complaint of bilateral tinnitus, hearing loss, low grade fever and weakness in bilateral lower limbs , which on imaging work up showed bilateral acoustic schwannoma, meningioma and small cord ependymoma giving the classical features of neurofibromatosis II along with unique features of cafe au lait spots, cutaneous neurofibromas, plexiform neurofibromas, and focus of altered signal intensity in white matter tracts of left frontal lobe which are unique to NF1. To our knowledge no such previous case report with overlapping features of both NF-1 and NF-2 has been described before.

Sphenoorbital Encephalocele and Globe Subluxation in a Case of Neurofibromatosis 1

Neurofibromatosis (NF) is a genetic abnormality that affects the cell growth of neural tissue, leading to tumor growths that impact skin, nervous system, eyes, and other organs. NF is divided into two primary subgroups: NF Type 1 (NF1) also known as Von Recklinghausen or peripheral NF and NF2 also known as bilateral acoustic NF and central NF. The common ophthalmic manifestations of NF1 include Lisch nodules, optic nerve glioma, and plexiform neurofibroma within the lid and retinal glial hamartoma. We present the case of a 45-year-old male NF1 patient who presented with pulsating eccentric proptosis and globe subluxation along with various other systemic and ophthalmic manifestations. In this case report, we will be highlighting the clinical and radiological findings of the patient.

Peripheral neuropathy in neurofibromatoses

WCN 2013 No: 2699 Topic: 7 Neuromuscular disorders Peripheral neuropathy in neurofibromatoses M. Poloni, R. Barbo. Neurosciences, HPG 23, Bergamo, Italy; Neurosciences, ICH Gavazzeni, Bergamo, Italy Neurofibromas are benign tumors which originate from peripheral nerves and are, together with others pathognomonic symptoms, a common finding in Neurofibromatosis 1 (NF1) conversely Neurofibromatosis 2 (NF2) or central neurofibromatosis is characterized by abnormal growth of Schwann cell tumors called schwannomas (SCH) at vestibular nerves, beyond meningiomas, ependimomas and SCHs of other cranial nerves or different Central Nervous System (CNS) tumors. NF1 is a genetic disorder transmitted thorough chromosome 17 due to neurofibromin alterations and abnormal tumors growth with rare Malignant Peripheral Nerve Tumors (MPNT), while NF2 is linked to merlin abnormalities and is at same genetically transmitted but through chromosome 22. Peripheral neuropathy (PN) appears rarely in NF1, ranging from 0 to 4.3 % of patients in different casistics, while retains only instrumental evidence in NF2 where mononeuropathy, generally as a foot drop or a facial palsy, is relatively common. Three interesting cases of important and distressing peripheral neuropathy, one affected by NF1 and two brothers affected by NF2, have been seen and studied at the NF Ambulatorial Center of Bergamo: we want to share the clinical and instrumental characteristics of these patients, discussing the differential diagnosis and arguing the different pathogenetic mechanisms. doi:10.1016/j.jns.2013.07.1666 Abstract WCN 2013 No: 2686 Topic: 7 Neuromuscular disorders Facial onset sensory and motor neuronopathy: A neurodegenerative TDP-43 proteinopathy? WCN 2013 No: 2686 Topic: 7 Neuromuscular disorders Facial onset sensory and motor neuronopathy: A neurodegenerative TDP-43 proteinopathy? E.P. Bosch, B.P. Goodman, J.A. Tracy, P.J.B. Dyck, C. Giannini. Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA; Neurology, Mayo Clinic Rochester, Rochester, MN, USA; Pathology, Mayo Clinic Rochester,

Genetic diseases affecting the eyelids

The molecular basis of a number of inherited diseases that affect the eyelids has been elucidated over the last two decades. Due to the vast number of these diseases, a clinician may become overwhelmed by the volume of data, making it difficult to incorporate newer information into his or her clinical practice. This article intends to review the recent developments of inherited diseases that affect the eyelids that a typical oculoplastic surgeon will encounter. This review proposes categorizing genetic diseases affecting the eyelids on rarity and whether the disease manifests itself at birth or later in life. Based on this classification system the following 10 diseases (the first five manifesting at birth, the last five later in life) are considered more likely to be encountered by the typical oculoplastic surgeon and reviewed in detail: blepharophimosis-ptosis-epicanthus inversus syndrome, congenital fibrosis of the extraocular muscles, lymphedema-distichiasis syndrome, neurofibromatosis type 1, congenital myasthenic syndrome, oculopharyngeal muscular dystrophy, chronic progressive external ophthalmoplegia, myotonic dystrophy, neurofibromatosis type 2, and basal cell nevus syndrome. The remaining known genetic disorders that affect the eyelids are considered less likely to be encountered by the typical oculoplastic surgeon and are listed in tabular form. It is prudent for the oculoplastic surgeon to be knowledgeable of inherited disorders that affect the eyelids to aid in accurate diagnosis, counseling, and treatment. The development of future therapies may at some point make treatment of these diseases no longer surgical. http://links.lww.com/COOP/A4.

Neurofibromatosis type 2 (NF2)

Other names: central neurofibromatosis; bilateral acoustic neurofibromatosis; bilateral acoustic neurinoma; bilateral acoustic schwannomas. Inheritance: autosomal dominant with almost complete penetrance; frequency is 3/10 newborns; neomutation represent 50% of cases; variable expressivity from mild disease through life (Gardner type) to severe condition at young age (Wishart type: with more than 3 tumours).

Neurofibromatosis

Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in an autosomal dominant fashion, this phacomatosis is classified into two genetically distinct subtypes characterized by multiple cutaneous lesions and tumors of the peripheral and central nervous system. Neurofibromatosis type 1 (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500 individuals and presents with a variety of characteristic abnormalities of the skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2), previously termed central neurofibromatosis, is much more rare occurring in less than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent in the late teens with a sudden loss of hearing due to the development of bi-or unilateral vestibular schwannomas. In addition NF2 patients may suffer from further nervous tissue tumors such as meningiomas or gliomas. This review summarizes the characteristic features of the two forms of NF and outlines commonalities and distinctions between NF1 and NF2.

Intracranial Calcification and Seizures: a Case of Central Neurofibromatosis

Periventricular calcification was found in an eight-year-old boy with seizures. The diagnosis of tuberous sclerosis was considered, but (like his mother) he has central neurofibromatosis. This condition must be considered in the differential diagnosis of children with intracranial calcification and seizures.

Extracranial meningioma of the parapharyngeal space: report of a case and review of the literature

Parapharyngeal tumours are frequently encountered in clinical practice and are often difficult to diagnose upon clinical examination due to the anatomic complexity of the region. We report a rare case of extracranial meningioma of the parapharyngeal space in a patient with no history of von Recklinghausen's disease, family history of meningioma or central neurofibromatosis (NF-2). The purpose of this report is to reiterate and emphasize the role of CT and MRI in the diagnosis of parapharyngeal masses, and to describe the characteristic radiological features of extracranial meningiomas.

Malignancy in a vestibular schwannoma. Report of a case with central neurofibromatosis, treated by both stereotactic radiosurgery and surgical excision, with a review of the literature

Malignant change in schwannoma is rare. Malignant change in a vestibular schwannoma (acoustic neuroma) is even more rare. This paper presents a case of rapidly growing vestibular schwannoma first treated by radiosurgery whose histopathology after surgical excision 42 months later showed malignant changes. Up to now, eight cases of malignancy in eighth nerve tumours have been reported, four of which, including the present case, had previously been treated with radiosurgery and four cases that had not received radiation. Thus, it would seem, the overall incidence is extremely low. Nevertheless, extreme vigilance and careful reporting continues to be necessary.

Loss of heterozygosity on chromosome 22q and 17p correlates with aggressiveness of meningiomas.

According to reported cytogenetic studies, there is a significant association between chromosomal aberrations and aggressiveness in meningiomas. With the method of restriction fragment length polymorphism analysis (RFLP), we examined tumor specific LOH on chromosome 17p and 22q in 30 cases of intracranial meningiomas. There were eight cases of meningiomas with aggressive characteristics, such as invasive meningioma, malignant meningioma, hemangiopericytic meningioma, and multiple meningiomas with central neurofibromatosis. Twenty-five of 30 cases (83%) were constitutionally heterozygous for at least one of the chromosome 22q DNA markers and sixteen of 25 informative cases (64%) displayed loss of heterozygosity (LOH). All of the 8 informative cases (100%) of meningiomas with aggressive characteristics, showed LOH on chromosome 22q whereas non-aggressive cases revealed LOH in eight of 17 informative cases (47%). At the loci on chromosome 17p, only two cases of malignant meningionas showed LOH. Our results suggest that the inactivations of putative tumor suppressor genes on chromosome 22q and 17p may correlate with aggressiveness and malignant transformation of meningiomas.

Cytogenetic analysis of a malignant triton tumor and a malignant peripheral nerve sheath tumor and a review of the literature

Cytogenetic analyses of malignant peripheral nerve sheath tumors (MPNST) and malignant triton tumors (MTT) are few to date. Two separate triton tumor specimens from one patient and a MPNST specimen from another patient, both with peripheral neurofibromatosis (NF-1, von Recklinghausen disease), showed complex near-triploid complements and partial deletion of the short arm of chromosome 1. Notably, a structural abnormality of chromosome 17 was detected in the MPNST, and loss of chromosome 22 was detected in the MTT. The genes for peripheral neurofibromatosis (NF-1) and central neurofibromatosis (NF-2) have been mapped to these two chromosomes respectively.

Retinal changes associated with neurofibromatosis 2

Neurofibromatosis (NF) is now known to be more than one disease. NF2, formerly classified as central neurofibromatosis, is characterized by bilateral vestibular schwannomas, previously termed "acoustic neuromas", and is much less common than NF1. Lens opacities at an early age have been described in approximately 85% of NF2 patients. To determine the frequency of retinal abnormalities in NF2 patients. We prospectively examined 15 consecutive patients who met the diagnostic criteria of NF2. We observed an epiretinal membrane in the macular or paramacular area in 12 of 15 patients, and a combined pigment epithelial and retinal hamartoma in the macula of one patient who also had an epiretinal membrane in the macula of the other eye. Additionally, 11 patients had central posterior cortical, subcapsular, or peripheral cortical lens opacities. Children or young patients with epiretinal membranes, combined pigment epithelial retinal hamartoma, and lens opacities that are not the result of other ocular disorders should have a neurologic evaluation and a careful family history for NF2.

CNS young investigator award lecture: Molecular analysis of the neurofibromatosis 2 tumor suppressor

Neurofibromatosis 2 (NF2), also known as bilateral acoustic neurofibromatosis or central neurofibromatosis, is a severe autosomal dominant disease characterized by the development of multiple nervous system tumors. The tumors of NF2, which include schwannomas, meningiomas and ependymomas, are histologically benign; however, their location and multiplicity led to great morbidity and mortality. These tumors commonly affect the general population in their isolated form, and have been found to undergo loss of chromosome 22 material in many studies; because of this the NF2 gene has been postulated to be a classic tumor suppressor. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins which we have named merlin. To define the molecular basis of NF2 in germline and tumor specimens, we have used single-stranded conformation polymorphism (SSCP) analysis to scan the exons of the NF2 gene. We have located and characterized underlying ca USAtive mutation in 21 of 33 unrelated affected individuals studied, and 32 of 38 schwannomas. DNA sequence analysis revealed that over 90% of NF2 mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. Current studies focus on relating the highly variable NF2 phenotype to its genotype, defining alternative NF2 related phenotypes, and elucidating the parental origin of new mutation in this disease.

Genetic alterations of brain tumors.

Genetic alterations of brain tumors were first detected in bilateral schwannomas (central neurofibromatosis Type II, NF 2) and sporadic vestibular schwannomas (acoustic neuromas). These hereditary tumors, which produce similar clinical syndromes due to the manifestation at the cerebellopontine angle, can be clearly distinguished by their different patterns of genetic changes [1-3]. At a later stage, the investigation of genetic alterations focussed upon neuroepithelial tumors. In particular, the controversial issue whether glioblastomas arise from either previously low grade astrocytomas, or de novo, or whether exist other developmental pathways, was assessed using different histological grades of astrocytic tumors as putative models for malignant tumor progression. In the following, investigations of brain tumor related genes, which provided several insights into modes of tumorigenesis and progression, are briefly reviewed. The importance of gene mapping is demonstrated by giving examples of advances that resulted from the knowledge of chromosome location of the genes involved.

A case of meningioangiomatosis without von Recklinghausen's disease

Meningioangiomatosis is rare disease and is classified as hamartoma in central neurofibromatosis. Unlike most cases of meningioangiomatosis, the very rare case reported here was not associated with von Recklinghausen's disease. We could find only 12 previous cases reported in the literature. A review was carried out of the clinical features, imaging characteristics, and histopathological findings in those 12 plus ours for a total 13 cases. Several types of convulsion were identified as clinical symptoms in 11 of the 13 cases. They were treated surgically. Prognosis was satisfactory in most cases. Proliferation of small blood vessels accompanied by endothelial cells with glial tissue as background and proliferation of fibroblasts or meningothelial cells in the perivascular space were observed to be the most frequent histopathological features.

Central Neurofibromatosis

An unusual case of central neurofibromatosis associated with a unilateral acoustic neuroma, multiple intracranial meningiomas, spinal neurofibroma and visceral involvement is presented. The progressive clinical course of this syndrome is described and discussed with a review of the relevant literature.

MR-tomographische Befunde kranialer Manifestationen der Neurofibromatose

Twelve patients with central neurofibromatosis underwent MR examination of the head. Among these, chiasma glioma was the most common CNS tumour (6/12). Seven patients had multifocal areas of increased T2-signal without mass effect predominantly involving the region of the basal ganglia. No corresponding CT abnormalities were present. These lesions may represent multifocal dysplasia and seem to be characteristic of central neurofibromatosis.

Preservation of hearing in neurofibromatosis 2

Preservation of hearing in the neurofibromatosis 2 (central neurofibromatosis) patient has been infrequently documented. This goal can be attained in selected patients and should be more frequently accomplished in the future with improved diagnostic capabilities and improved surgical techniques. We report three patients in whom this elusive goal has been accomplished.

Radioimmunoassay of glioma-associated antigen in cerebrospinal fluid and its usefulness for the diagnosis and monitoring of human glioma

Quantitative determination of human glioma-associated antigen in cerebrospinal fluids (CSFs) obtained from 66 patients with a variety of neurological diseases was performed by solid-phase radioimmunoassay with a monoclonal antibody (G-22). In this system, the minimum detectable amount of the antigen in the CSF was 8 ng/ml. It was demonstrated that CSF diagnosis of glioblastoma might be possible in the case of small tumors with a diameter of less than 2 cm. CSFs obtained from all 18 patients with glioma were positive and the level varied from 11.2 to 186.1 ng/ml. The antigen level in the cystic fluid of the tumor was higher than that in CSF. There was a tendency for the antigen level in CSF to be correlated with the tumor size and the type of histology. The malignant types of glioblastoma or medulloblastoma showed higher levels than the benign type of ependymoma and astrocytoma. Most types of non-gliomatous brain tumor were negative except immature teratoma, meningioma with central neurofibromatosis, and metastatic brain tumor from lung cancer. We also noted that tumor progression or regression of malignant glioma could be predicted by the monitoring of the antigen in the CSF.