The different forms of neurofibromatosis

In the last two decades our knowledge of the natural history, genetics and management of the different forms of neurofibromatosis has changed. Of the numerical classifications of neurofibromatosis proposed in the past, only neurofibromatosis type 1 (Nf1) and neurofibromatosis type 2 (Nf2) have been shown to be distinct at clinical and molecular levels. Mosaicism has been demonstrated both in patients with Nf1 and in patients with Nf2, and features of segmental or mosaic Nf1 and Nf2 have been defined. The outlying phenotypes and the molecular genetics of other, rarer, types of neurofibromatosis have been delineated: these are hereditary spinal neurofibromatosis, Schwannomatosis, familial intestinal neurofibromatosis, autosomal dominant ”café-au-lait spots alone”, autosomal dominant ”neurofibromas alone”, Watson syndrome, Noonan/neurofibromatosis syndrome and the so-called syndrome of multiple naevi, multiple schwannomas and multiple vaginal leiomyomas. In this article I will review the different forms of neurofibromatosis, focusing on those aspects that most commonly challenge the neurosurgeon. Received: 3 February 1999     

MRI of Lumbar and Sacral Plexus Nerve Sheath Tumours

Seven patients with peripheral nerve sheath tumours affecting the lumbo-sacral plexus were examined with MR imaging utilizing a 1.5T magnet and spin echo pulse sequences. The majority of tumours were homogeneous in signal intensity and isointense with adjacent muscle on T₁ weighted images and showed markedly increased signal intensity on T₂ weighted images with central areas of relatively low signal intensity. An attempt to obtain a pathological correlation with the areas of low signal on T₂ weighted images was unsuccessful. The use of Gadolinium DTPA in one patient resulted in irregular enhancement of both a neurogenic sarcoma and smaller neurofibromas. The multiplanar imaging capabilities, high soft tissue contrast, non-invasiveness, lack of ionizing radiation and the characteristic appearance of neural tumours makes MR ideal for imaging these lesions.     

Malignant peripheral nerve sheath tumor of the back

A 65-year-old woman developed a tumor on the medial aspect of the lumbosacral spine. The diagnosis on biopsy was neurogenic sarcoma, T3N0M0. Despite wide surgical excision and regular follow-up, the patient developed a local recurrence requiring several supplementary operations before her death 4 years after the initial diagnosis. This case illustrates the highly aggressive and recurrent nature of these rare neurogenic tumors; they require early multidisciplinary management and regular careful follow-up. Received: 13 November 1999 / Accepted: 23 February 2000     

神经纤维瘤病I型的MRI研究

目的：回顾神经纤维瘤病I型（NF1）患者MRI表现，分析MR扫描序列及其诊断价值，以建立合适的MR成像方案，为NF1影像诊断提供有价值的依据。方法：对30例临床确诊为NF1患者采用本组MR成像方案进行扫描，主要包括：轴面SE序列T2WI；平扫矢状面SE脉冲序列T1WI；增强轴面或矢状面SE脉冲序列T1WI；轴面或冠状面液体衰减反转恢复（FLAIR）序列，同时分析病变的发病部位、数目、形态、信号的变化和病变的强化情况等。结果：MRI可见下列3种表现：（1）多发性脑内错构瘤：30例中25例在SE脉冲序列T2WI和FlAIR脉冲序列见高信号病灶，病灶主要位于苍白球、小脑和脑干。另外，25例中20例可见海马回、海马旁回等区晕状高信号改变。（2）视通道或下丘脑胶质瘤：视神经、视交叉增粗、扭曲；视交叉或下丘脑肿块，SE脉冲序列T2WI和FlAIR序列表现为不规则分叶状混杂信号肿块，在增强SE脉冲序列T1WI有明显不规则强化。（3）脊柱多发性神经纤维瘤：SE脉冲序列T2WI和脂肪抑制短时反转恢复（STIR）序列显示高信号沿脊神经分布的多发性肿瘤。结论：MRI能够作为1种 常规的影像检查方法对NF1患者进行诊断和追踪。本组MR成像方案能较好地显示NF1的多发性或多灶性病变。     

Volume growth rate of acoustic neurinomas

Summary Of 79 acoustic neurinomas seen between June 1980 and June 1984, at least two CT scans were available for each of 23 tumours (21 patients); the scans were performed at intervals of at least 6 months. The volume growth rate of the tumours was either moderate, with a volume doubling time ranging from 205 to 545 days, or slow, with a doubling time ranging from 1090 days to no observable growth. No single clinical, radiological or histological feature correlated with any type of growth rate. however, some conclusions were drawn. If a primary CT scan is negative, at least 1 year should elapse before it is worthwhile taking another scan, even though audiological findings suggest growth; after an an apparently radical removal, at least 3 years should elapse before a check CT scan is worthwhile; and if a small acoustic neurinoma is diagnosed, but for some reason not operated upon, a second CT scan should be carried out 1 year later in order to reassess the case.     

Gastrointestinal involvement in neurofibromatosis: Angiographic presentation

A large neurofibroma associated with gastrointestinal hemorrhage was demonstrated by visceral arteriography. The findings are correlated with those of resected pathologic specimen.     

Developmental dosing with a MEK inhibitor (PD0325901) rescues myopathic features of the muscle-specific but not limb-specific Nf1 knockout mouse

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder While NF1 is primarily associated with predisposition for tumor formation, muscle weakness has emerged as having a significant impact on quality of life. NF1 inactivation is linked with a canonical upregulation Ras-MEK-ERK signaling. This in this study we tested the capacity of the small molecule MEK inhibitor PD0325901 to influence the intramyocellular lipid accumulation associated with NF1 deficiency. Established murine models of tissue specific Nf1 deletion in skeletal muscle (Nf1_MyoD^?/?) and limb mesenchyme (Nf1_Prx1^?/?) were tested.Developmental PD0325901 dosing of dams pregnant with Nf1_MyoD^?/? progeny rescued the phenotype of day 3 pups including body weight and lipid accumulation by Oil Red O staining. In contrast, PD0325901 treatment of 4?week old Nf1_Prx1^?/? mice for 8?weeks had no impact on body weight, muscle wet weight, activity, or intramyocellular lipid. Examination of day 3 Nf1_Prx1^?/? pups showed differences between the two tissue-specific knockout strains, with lipid staining greatest in Nf1_MyoD^?/? mice, and fibrosis higher in Nf1_Prx1^?/? mice.These data show that a MEK/ERK dependent mechanism underlies NF1 muscle metabolism during development. However, crosstalk from Nf1-deficient non-muscle mesenchymal cells may impact upon muscle metabolism and fibrosis in neonatal and mature myofibers.     

Neurofibromatosis type 2 service delivery in England

Neurofibromatosis type 2 (NF2) is a complex disease characterized by the development of multiple schwannomas, especially vestibular schwannomas, as well as other types of benign tumours including meningioma and spinal ependymoma. Due to its multisystem nature, the management of NF2 requires a multidisciplinary approach. In England, the delivery of care for NF2 patients has been centralized to four-“hub” centres in Manchester, Cambridge, Oxford and London each having associated “spoke” centres. Each centre has a core multidisciplinary team consisting of genetics, otolaryngology, neurosurgery, paediatrics, neurology, audiology, radiology, psychology, physiotherapy, specialist nurses and administrative staff. In addition, the core team has access to plastic surgery, ophthalmology, peripheral nerve surgery and adult and paediatric oncology. There are weekly multidisciplinary clinics each with six to eight patients. Each patient is discussed during a team meeting and the management decisions that are made are then discussed with the patients. All patients are reviewed at least annually and have annual head magnetic resonance imaging (MRI) and three yearly spinal MRI. Annual audiological assessment is performed. Cochlear implantation and auditory brainstem implantation are offered if indicated. Surgery, stereotactic radiosurgery and bevacizumab therapy are available for the management of intracranial and spinal tumours. The integration of the service in England has provided significant benefits to patient care and, in the long term, will provide robust patient outcome data that will provide an evidence base to assist in optimizing management of patients with NF2.     

Childhood and adolescent meningiomas: a report of 38 cases and review of literature

Summary Background  The aim is to study the clinical, radiological and pathological features of childhood and adolescent meningiomas and analyse outcome prognosticators. Method  A retrospective analysis of the case records of patients less than 20 years of age operated for a meningioma in our institute since 1982 was performed. The variables analysed included age, sex, presentation, associated neurofibromatosis (NF), imaging characteristics, extent of resection and histopathology. Results  The study group included 20 males and 18 females with a mean age of 15.53 years. Eleven children (28.9%) had evidence of NF of whom three had NF2 with bilateral vestibular schwannomas. The common presenting symptoms were seizures (76.3%), raised intracranial tension (71%), and focal neurological deficits (39.4%). The location of the operated tumours were as follows: ten skull base (24.4%), ten falx/parasagittal (24.4%), eight spinal (19.5%), five convexity (12.2%), three posterior fossa (7.3%), three intraventricular (7.3%) and two optic nerve sheath (4.9%). Two children (4.9%) had cystic meningiomas. Grade I excision was achieved only in twenty tumours (48.8%). On histopathology, thirty (73.2%) were grade I, nine (21.9%) were grade II and two (4.9%) were grade III meningiomas. Seven tumours recurred of which six were located at the skull base. During the mean follow up period of 4.74 years, the majority, 32 (84.2%) had a good outcome and five (13.2%) had a poor outcome. One child (2.6%) expired due to post-operative sepsis. Conclusion  Childhood meningiomas are uncommon but not rare lesions with a marginal male predominance. Absence of large series with long follow up precludes any definite conclusions on the clinical course and outcome. Uniform observations made in different series including ours, include a higher incidence of the skull base location and tumours with atypical histopathology. Favourable prognostic factors include younger age (<than 10 years), superficial location, total excision and absence of neurofibromatosis. Location and extent of excision appear to be more important than histopathology grade in predicting outcome.     

Benign retroperitoneal schwannoma presenting as colitis： A case report

We report a case of a patient presenting with clinical, radiological and endoscopic features of colitis due to a compressive left para-aortic mass. Total open surgical excision was performed, which resulted in complete resolution of colitis. Histopathology and immunohistochemistry revealed benign retroperitoneal schwannoma. These neural sheath tumors rarely occur in the retroperitoneum. They are usually asymptomatic but as they enlarge they may compress adjacent structures, which leads to a wide spectrum of non-specific symptoms, including lumbar pain, headache, secondary hypertension, abdominal pain and renal colicky pain. CT and MR findings show characteristic features, but none are specific. Schwannoma can be isolated sporadic lesions, or associated with schwannomatosis or neurofibromatosis type Ⅱ （NF2）. Although they vary in biological and clinical behavior, their presence is, in nearly every case, due to alterations or absence of the NF2 gene, which is involved in the growth regulation of Schwann cells. Both conditions were excluded by thorough mutation analysis. Diagnosis is based on histopathological examination and immunohistochemistry. Total excision is therapeutic and has a good prognosis. Schwannomatosis and NF2 should be excluded through clinical diagnostic criteria. Genetic testing of NF2 is probably not justified in the presence of a solitary retroperitoneal schwannoma.