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Neurofibromatosis 2 is an autosomal-dominant disease, which is characterized by vestibular schwannomas, cataract, retinal hamartomas as well as tumors of the peripheral and central nerve system, demonstrating a variety of expression. The ophthalmologist plays an important role in making the diagnosis, as several ocular manifestations may be shown during childhood, before tumors of the central nerve system become symptomatic. An early diagnosis of NF 2 may prevent deafness by early surgical intervention. Due to primary and secondary reasons such as age-related processes, different sensations like hearing or vision may be compromised. Neuropathy may lead to vestibular disturbances and loss of muscle control. Therapeutic options include cataract surgery, implantation of cochlear or brainstem implants as well as conservative therapy of the ocular surface in paresis of the VIIth cranial nerve or learning to read from the lips. The human NF2 gene was cloned from chromosome 22 in 1993. The major part of the genetic alterations described so far are point mutations as well as deletions or insertions in or around the exons. Geno-phenotype correlations allow some predictions of the course of the disease to be made.

Aim: The aim of this study was to determine the malformations of the maxillary sinus in neurofibromatosis type 1 patients (NF1)., Material and Methods: Twenty-two patients with NF1 were investigated clinically and radiologically: 11 had an unilateral trigeminal plexiform neurofibroma and 11 had multiple cutaneous neurofibromas. The histological type of NF was ascertained in all cases following tumor resections. The malformation of the maxillary sinus was assessed on plain radiographs and computed or magnetic resonance tomograms. Intraindividual side comparison was used to judge the size of the sinus and its position in the midface., Results: In patients with cutaneous neurofibromas the maxillary sinus appeared symmetrical in size and position. The pneumatization of the sinus had no abnormalities on the radiographs. Malformations of the maxillary sinus were restricted to plexiform neurofibromas. On the side affected by a plexiform NF, the sinus appeared hypoplastic and caudally displaced due to an enlarged ipsilateral orbit. The expansion of the sinus to the lateral side was impaired, obviously due to tumor masses. Consecutively, the alveolar process of the affected side was also displaced leading to a complex malocclusion., Discussion: Malformations of the face are frequently presented as case reports in the literature. Emphasis is given to the elephantiasis-like tumor growth of the face in certain patients with NF1. The underlying pathology has not yet been fully understood. This report provides evidence that in the midfacial region the overgrowth is predominantly caused by the plexiform neurofibroma itself and that the bones can even be hypoplastic and show scoliosis-like malformation compared to the nonaffected side. These findings are relevant when debulking procedures of the face are planned for NF1 patients.

Background: Optic gliomas are frequently associated with neurofibromatosis type 1 (NF1) and belong to the diagnostic criteria of NF1. Different growth rates require differentiated strategies for screening and observation., Patients and Methods: 29 patients (25 children < 11 years, 4 adults > 18 years) with visual pathway tumors and NF1 were examined neurologically, ophthalmogically, by means of MRI and VEP. Results were set into context with preceding investigations (mean follow up time 6.5 years)., Results: 11 children showed a stable condition, 14 an unfavorable process with substantial loss of vision. Children with an unfavorable process showed a lower age at diagnosis (3.2 versus 5.8 years; p < 0.05), more frequently strabism (11/14 versus 1/11; p < 0.05), optic atrophy (12/14 versus 1/11; p < 0.05), pathological VEP (9/9 versus 2/10; p = 0.001), visual field defects (9/9 versus 1/9) and involvement of the optic chiasm (11/14 versus 3/11; p < 0.05) than children with a stable condition. 3 of 4 adults had no visual symptoms despite involvement of the optic chiasm., Conclusions: The crucial prognostic factor is the patient's age at the time of diagnosis. Optic gliomas which become symptomatic in early childhood (< 6 years) grow rapidly and require frequent ophthalmologic investigations and MRI. Tumors diagnosed in late childhood (> 6 years) do not progress, allowing for gradual extension of intervals between ophthalmological investigations.

Background: Neurofibromatosis 2 (NF2) is a rare autosomal dominant disorder (prevalence 1:37.000) associated with changes in tumor suppressor genes. Intraocular manifestations have been reported as subcapsular cataract, retinal hamartomas, epiretinal membranes, keratopathy in facial palsy, and tumors of the nerves I-V are typical ocular manifestations of NF2., Patients and Materials: We prospectively examined 7 patients who met the diagnostic criteria of NF2 with regard to retinal changes using fluorescence angiography and red-free fundus photography., Results: In four patients, we found window defects of the pigment epithelium in the macular or paramacular areas. In one patient we observed a combined pigment epithelial and astrocytic hamartoma. A choked papilla was found in two patients., Conclusions: Presumably, retinal changes in NF2 occur more frequently than has been assumed previously. Our results confirm that in NF2 patients more attention should be paid to abnormalities of the optic disk, the retina and the choroid.

Neurofibromatosis Type 1 and 2 (NF1 und NF2) are different forms of neurofibromatosis, well defined both clinically and genetically. In absence of typical clinical features of NF1 (café-au-lait-spots, cutaneous neurofibromas, Lisch-nodules) or NF2 (vestibular schwanoma) clinical classification is often not possible. Neurofibromas are more common in NF1 and schwannomas are typical for NF2, but pathological histology does not provide sufficient evidence for diagnosis. We describe 14 patients who presented with the clinical picture of multiple spinal tumours. Detailed family history, exact clinical examination including an ophthalmological examination led to the diagnosis of NF2 in four cases. Mutation analysis confirmed the diagnosis of NF2 in one case by identification of a 163 base pair deletion in the NF2 transcript. To investigate the expression of schwannomin and neurofibromin we stained tumour paraffin sections of six patients with antibodies against peptides of the NF1 and the NF2 protein. Based on preserved immunoreactivities we were able to exclude diagnosis of NF1 in three and NF2 in two cases. In four patients the clinical symptoms could confirm the diagnosis of schwannomatosis. Combining the results of clinical, neurogenetical and immunohistochemical examinations we could diagnose NF1 or NF2 in ten patients in total. Immunoreactivity led to the suggestion of NF2 in two patients; the other two patients whose tumours were not stained so far, could as yet not be classified for NF.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease of high penetrance and variable expression. Epidemiologic data on craniofacial manifestations are still lacking. Up until now 74 patients with NF1 have been treated at the Department of Oral and Maxillofacial Surgery of the University of Hamburg. Forty-two patients presented periorbital and orbital neurofibromas varying in extension and in the severity of findings of the affected site. Surgical therapy is mainly based on tumour reduction, frequently combined with face-lifting. In our experience neurofibromas of the neck tend to be pseudo-encapsulated, facilitating the preparation of the tumour. On the other hand, identification and preparation of diffuse infiltrating neurofibromas in the trigeminal nerve region are difficult and local recurrence must be expected.

In dermatological practice, itch is the leading symptom of many skin diseases with a variety of psychophysiological aspects. However, a complete inventory for the qualitative evaluation of these central nervous factors is missing, whereas in pain research, the McGill Pain Questionnaire is well established for this purpose. Thus, therapeutic effects of antipruritic agents are only incompletely described by visual analog scales or parameters of skin physiology. Here, a questionnaire modified in analogy to the McGill pain questionnaire is presented, developed in cooperation between dermatologists and neurophysiologists.

Background: Neurofibromatosis type 2 (NF2) is a disorder with autosomal dominant inheritance which leads to tumor growth in the central and peripheral nervous system. In affected adult patients there is a typical association with ocular abnormalities like juvenile cataract., Methods: Ophthalmologic investigation was carried out in ten children aged one to fourteen years with suspected NF2. The diagnosis was confirmed by further clinical examination and-in one patient-by segregation analysis., Results: Nine of these ten children showed ocular abnormalities such as juvenile subcapsular cataracts, retinal hamartomas, optic nerve sheath tumors, fibrotic maculopathies as well as one case of a perineural calcification of the optic nerve and one case of a cerebral hamartoma on the ground of the third ventricle., Discussion: In six children ophthalmological symptoms were the presenting symptom of the disease. The knowledge of these symptoms allows for the diagnosis of NF2 in children who present with isolated ocular deficits or with other typical criteria of the disease. The early diagnosis of the disease may lead to an improved prognosis with regard to preservation of hearing by surgery of bilateral vestibular schwannoma which occur in more than 90% of the NF2-patients.

Bilateral vestibular schwannomas (VSs) are the hallmark of neurofibromatosis type 2 and the crucial criteria for the diagnosis of this autosomal dominant disorder according to the criteria of the National Institutes of Health Consensus Statement. We describe three patients without VSs aged 47, 52 and 69 years, in whom a NF2 gene carrier status was diagnosed by spinal tumors, a cataract and schwannoma of cranial and peripheral nerves. In one case the diagnosis was ascertained by mutation analysis, which revealed a 163bp deletion in the NF2 cDNA, and by the fact that two daughters had the same deletion and NF2 according to the NIH criteria. Our finding suggests that patients with spinal tumors, multiple brain tumors, associated neurinomas or cataract might be carriers of a mutated NF2-gene. The study suggests that the NIH criteria are too restrictive, since NF2 seems to show up for a broader spectrum of phenotypes.

Neurofibromatosis (NF) is one of the most frequent autosomal-dominant hereditary disorders. The molecular-genetic differentiation of NF 1 and NF 2 has important implications for the ophthalmologist. Among 80 patients with NF 1, Lisch nodules were diagnosed in 83% as typical criteria for the disease. In 6 patients who did not meet the NIH criteria for NF 1 and NF 2, the ophthalmological investigation showed no cataracts or Lisch nodules; thus, the ophthalmological examination can help to confirm a subtype of NF. In 8 out of 22 NF 2 patients a juvenile posterior subcapsular cataract was diagnosed. Our examination demonstrates that the diagnostic value of lens opacities in NF 2 patients--especially for early detection of the disease--must be clarified, especially with regard to the fact that there were no patients with incipient cataract and no neuroradiological criteria for the disease.

Neurofibromatosis is one of the most frequent autosomal-dominant hereditary disorders. Neoplastic, dysplastic and dysraphic lesions characterize the disease from the viewpoint of a neurologist. Depression, suicide, emotional instability, learning disability and behavior disorder are important aspects for the neuropsychiatric evaluation. Treatment of the patients will be facilitated by following the diagnostic criteria and by an interdisciplinary approach to diagnosis. The gene-molecular differentiation of NF I and NF II provides a basis for a more profound understanding of the disease which allows for more than just the clinical description. Cloning of the gene of NF I will give the possibility of predictive diagnosis of NF I. At present an indirect prenatal diagnosis of the genetic disorder is possible by flanking markers of NF I.

37 patients with documented neurofibromatosis (15 children and 22 adults) had MR examination of the cerebrum. To determine the clinical relevance of signalintense foci in MRT EEG, BAEP and a neuropsychological test batteries was carried out. Our investigations showed that signalintense areas, which possibly represent dysplastic lesions, did not correlate with neurological deficits, epileptic seizures and cognitive disabilities. It remains unclear whether these lesions are of a potential malignancy.

Investigation of subclinical infections with Borrelia burgdorferi in risk groups in Switzerland, Austria and southern Germany showed an infection rate of 16%-27%. Random samples of patients admitted to the neurological department of a hospital on the outskirts of Hamburg gave the following results: in 100 sera there was in 27% a positive Elisa-test, in 77 sera the IFT-test was positive in 13%, and in 210 sera 6% showed a positive IFT-test after absorption; the IFT- and IFT-Abs. were compared in 15 sera. The investigation confirms that subclinical infection with Borrelia burgdorferi in northern Germany is not uncommon. The fact that increased levels of IgG and IgM antibodies do not necessarily mean the presence of an acute or chronic disease should be remembered in making decisions about treatment.

Determination of serum prolactin concentration was carried out under standardized conditions on 70 hospitalised patients after different types of epileptic, syncopal and psychogenic seizures. In cases of unconsciousness of unknown cause and of unobserved seizures there is evidence that the determination of postictal prolactin may help to clarify the diagnosis. Excluding patients with epileptic seizures due to alcohol withdrawal only in 70% of the patients was there a significant elevation of serum prolactin. The clinical procedure thus appears to be of importance also in the differential diagnosis of psychogenic seizures. Patients with epileptic seizures due to alcohol withdrawal showed an elevated prolactin concentration in only 45% of cases. Whereas an elevated serum prolactin level indicates the occurrence of a grand mal seizure, a normal prolactin level does not positively exclude epileptic seizures.

15 patients aged 1-39 years with documented neurofibromatosis had MR examinations of the cerebrum within the scope of a basic diagnosis and therapy programme. Clinical examination did not lead to pathologic findings for 7 of the patients; 3 patients suffered from general developmental disabilities. A neurologico-psychiatric examination showed pathological findings in 5 patients. Signal-intense foci in proton density and T2-weighted MR images were found in the globus pallidus, thalamus, hippocampus, cerebellum and midbrain. In 2 patients, these foci could be found as well in T1-weighted images. Differentiation between gliosis areas and low grade astrocytomas was not possible in MR.