The earliest descriptions of neurofibromatosis or neurofibromatosis-like disease date back to the thirteenth century in Austria and to the sixteenth century (Mulvihill 1990). In 1822, Wishart, a Scottish surgeon, published the first description of a deaf and blind boy with multiple tumours of the dura and the cranial nerves, which combination has long been recognized as the principal form of neurofibromatosis (Rubinstein 1986). Virchow reported in 1847 the first family with neurofibromatosis in several generations (Huson et al. 1989).
In 1882, Friedrich von Recklinghausen, a German pathologist and professor in Strassburg, presented in his article " Ueber die multiplen Fibrome der Haut und ihre Beziehung zu den multiplen Neuromen" two autopsied patients and recognized the neural origin of the neurofibroma, which is the most common lesion in NF (Crump 1981). This identification caused the disorder also to be known as von Recklinghausen´s disease. The first systematic genetic stydy of NF was carried out by Thomson in 1900. Borberg (1951) and Crowe (1956) reported the first large clinical studies of neurofibromatosis. They also established the autosomal dominant mode of inheritance of neurofibromatosis and the high penetrance of the disease and showed that about half of the probands represented new mutations. Since then, several clinical and genetic poppulation-based studies of neurofibromatosis have been performed, and the etiology and genetics of the different forms of NF have been evaluated.
The significance of central nervous system symptoms and lesions in neurofibromatosis became apparent soon after the recognition of this disorder. Before the era of CT and MRI, imaging information of the central nervous system was obtained by plain radiographs and tomography of the skull and the orbits. PEG with polytomography, angiography, orbital phlebography and radionuclide scanning were also used, and only secondary signs of pathological conditions could be seen, such as enlargement of the skull and orbital foramina, thinning, erosion or sclerosis of bone, pathological vascular markings, sutural widening or defects, orbital deformities and calcifications. The neuroradiological methods of investigating tumours involving the optic pathways varied according to whether the lesion was intraorbital or intracranial. (Savoiardo et al. 1981). For spinal lesions, plain films, tomography, myelography with either negative or positive contrast medium, angiography and radionuclide scanning were used. Abnormal spinal curvature, bony anomalies and secondary lesions, such as widening of the intervertebral foramina or the spinal canal, could be easily detected, but it was not possible to decide if the widening was due to a tumour or to dural ectasia.
Several lesions of NF, both cerebral and spinal, have become visible or their visualization has been greatly facilitated by the modern imaging methods, CT and especially MR. T2 hyperintense brain lesions and intramedullary tumours in both NF1 and NF2 have been recognized, and the extent of the lesions, e.g. spinal neurofibromas, can now be easily evaluated with MRI. The use of intravascular contrast agents has further improved the diagnosis of CNS lesions. Imaging of the CNS and follow-up of the disease can be performed with MRI without any risk of ionizing radiation, which is important especially in children.
Neurofibromatosis was traditionally divided into two entities, central NF and peripheral NF, until it was established in the 1980´s that these entities represent two entirely different clinical disorders due to mutations in two different genes. The National Institute of Health (NIH) Consensus Development Conference held in1987 in Bethesda, Md, USA (NIH 1988) suggested, on the basis of clinical features, two distinct types to be differentiated: NF1 and NF2, and defined the diagnostic criteria for both of them. NF1 was synonymous to the classical von Recklinghausen´s disease, while NF2 corresponded to the predominantly intracranial (central) type of neurofibromatosis.
Riccardi (1987) refined the classification further and suggested that neurofibro-matosis should be divided into eight subgroups. NF1 (von Recklinghausen NF or peripheral NF) has as its major features multiple café-au-lait spots, peripheral neurofibromas and pigmented iris hamartomas (Lisch nodules). NF2 (central NF or bilateral acoustic neurofibromatosis) is characterized by bilateral acoustic neurinomas, meningeomas and spinal medullary tumors. NF 1 and NF2 together account for more than 99% of all cases on neurofibromatosis (Braffman & Naidich 1994).
More recently, Carey and Viskochil (1999) proposed a further classification of NF based on both clinical and molecular genetic criteria. Other forms than NF1 and NF1 are cosiderered as variants of NF, e.g. segmental neurofibromatosis (former NF5) manifests in restricted areas of the body, usually unilaterally.
Of all the different types of neurofibromatosis, NF1 or classical neurofibromatosis or von Recklinghausen´s disease accounts for 90% of all cases (Huson 1987). Its diagnostic criteria were established in consensus meetings in 1987 and 1997, and are now used universally. For the diagnosis of NF1, the patient should fulfil two or more of the following criteria (Gutmann et al. 1997):
six or more café-au-lait macules with a diameter of > 1.5 cm in postpubertal and > 0.5cm in prepubertal individuals
two or more neurofibromas of any type, or one plexiform neurofibroma
multiple freckles in the axillary area or the groins
optic glioma
two or more Lisch nodules (iris hamartomas)
a distinct osseous lesion, such as sphenoid dysplasia or thinning of the bone cortex with or without pseudoarthrosis
an affected first-degree relative (parent, sibling, offspring) with NF1
Most of the diagnostic criteria are well visible and easy to use. CNS-related criteria have not been needed, although T2 hyperintensities of the brain have been suggested as an additional diagnostic criterion (Curless et al. 1998, De Bella et al. 2000a)