Gunnar Nyberg

Fractionated, stereotactic proton beam treatment of cerebral arteriovenous malformations

Objectives – To evaluate the therapeutic efficiency and adverse effects of stereotactic proton beam treatment of cerebral arteriovenous malformations (AVM).

PET-Methionine of Skull Base Neuromas and Meningiomas

Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as neuromas or meningiomas were studied with positron emission tomography (PET) using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the uptake of methionine in the tumours increased more rapidly and reached a higher level, and showed a slow decline after a peak occurring about 5 min after the injection. All the meningiomas exhibited considerably higher accumulation of the tracer compared with the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding structures (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in all meningiomas, which were all of the syncytial type. The neuromas showed lower contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean 1.48). Some neuromas displayed an irregular pattern with regions of decreased tracer uptake corresponding to small cystic areas within the neuroma. There was no overlap in methionine uptake between the two tumour groups. The results indicate that PET-methionine may contribute to the evaluation, treatment planning and follow-up of patients with skull base meningiomas and neuromas.

Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker

76Br-bromodeoxyuridine has previously been suggested as a PET tracer to characterize proliferation potential. However, in animal studies a large fraction of the tissue radioactivity is due to 76Br-bromide, which remains extracellular for extensive periods and contributes significantly to the level of radioactivity. The present project aimed at investigating whether in human brain tumors, sufficient amounts of 76Br-bromodeoxyuridine would be incorporated into DNA, to motivate further attempts with this tracer. Eight patients with brain tumors: 3 meningiomas, 2 astrocytoma grade IV, 1 astrocytoma oligodendroglioma grade II-IV and 2 metastases, were examined with PET and 76Br-BrdU on three occasions: immediately after injection of the tracer, at 4-6, and at 18-20 hours after administration. After the first PET study, diuresis was introduced and maintained for about 12 hours. About 20 hours after tracer administration, 200 mg/m(2) bromodeoxyuridine was administered to 7 patients median 5.8 (range 1-22) hours prior to operation allowing the immunohistochemical analysis of the proliferation potential. During the operation, tumor samples were taken and radioactivity in DNA extracted and measured. The uptake of radioactivity was higher in the tumors than in brain parenchyma. However, in the operative samples only 1-27% (average: 9%) of the radioactivity was found in the DNA fraction. The plasma radioactivity remained high throughout the study with only minimal signs of elimination by the diuresis. 76Br-BrdU is extensively metabolized to 76Br-bromide, and only a minor fraction of the radioactivity is found in the DNA fraction, making it unlikely that this tracer can be used for assessment of proliferation potential.

High-resolution array-CGH profiling of germline and tumor- specific copy number alterations on chromosome 22 in patients affected with schwannomas

Schwannomas may develop sporadically or in association with NF2 and schwannomatosis. The fundamental aberration in schwannomas is the bi-allelic inactivation of the NF2 gene. However, clinical and molecular data suggest that these tumors share a common pathogenetic mechanism related to as yet undefined 22q-loci. Linkage studies in schwannomatosis, a condition related to NF2, have defined a candidate 22q-locus and excluded the NF2 gene as the causative germline mutation. Thus, analysis of aberrations in schwannomas may lead to the identification of putative gene(s) involved in the development of schwannoma/schwannomatosis. We profiled a series of 88 schwannomas and constitutional DNA using a tiling path chromosome 22 array. Array-CGH is a suitable method for high-resolution discrimination between germline and tumor-specific aberrations. Previously reported frequencies of 22q-associated deletions in schwannomas display large discrepancies, ranging from 30% to 80%. We detected heterozygous deletions in 53% of schwannomas and the predominant pattern was monosomy 22. In addition, three tumors displayed terminal deletions and four harbored overlapping interstitial deletions of various sizes encompassing the NF2 gene. When profiling constitutional DNA, we identified eight loci that were affected by copy number variation (CNV). Some of the identified CNVs may not be phenotypically neutral and the possible role of these CNVs in the pathogenesis of schwannomas should be studied further. We observed a correlation between the breakpoint position, present in tumor and/or constitutional DNA and the location of segmental duplications. This association implicates these unstable regions in rearrangements occurring both in meiosis and mitosis.

Long-term Mobile Phone Use and Acoustic Neuroma Risk.

Background: There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. Methods: We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). Results: Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. Conclusions: The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

Role of Tobacco Use in the Etiology of Acoustic Neuroma

Two previous studies suggest that cigarette smoking reduces acoustic neuroma risk; however, an association between use of snuff tobacco and acoustic neuroma has not been investigated previously. The authors conducted a case-control study in Sweden from 2002 to 2007, in which 451 cases and 710 population-based controls completed questionnaires. Cases and controls were matched on gender, region, and age within 5 years. The authors estimated odds ratios using conditional logistic regression analyses, adjusted for education and tobacco use (snuff use in the smoking analysis and smoking in the snuff analysis). The risk of acoustic neuroma was greatly reduced in male current smokers (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23, 0.74) and moderately reduced in female current smokers (OR = 0.70, 95% CI: 0.40, 1.23). In contrast, current snuff use among males was not associated with risk of acoustic neuroma (OR = 0.94, 95% CI: 0.57, 1.55). The authors’ findings are consistent with previous reports of lower acoustic neuroma risk among current cigarette smokers than among never smokers. The absence of an association between snuff use and acoustic neuroma suggests that some constituent of tobacco smoke other than nicotine may confer protection against acoustic neuroma.

Surgical Treatment of Patients With Facial Neuromas : A Report of 26 Consecutive Operations

Objective: To analyze surgical treatment and outcome in patients with facial neuromas at a tertiary referral hospital. Study Design: A chart review of 26 patients treated between 1971 and 2006, with questionnaire follow-up ranging from 2 to 19 years. All patients except one were operated with radical tumor removal approaches. Results: Approximately 54% of the patients presented with symptoms related to the VIIth cranial nerve (facial palsy and facial spasm), 58% with symptoms related to the VIIIth cranial nerve (hearing deficit, tinnitus, and vertigo), and 8% related to the Vth cranial nerve (facial pain and facial sensory deficit). Approximately 39% presented with no facial symptoms. Twenty-one patients received a facial nerve graft from the greater auricular nerve or the sural nerve; 1 patient had an accessory-facial anastomosis. One patient had a subtotal tumor removal preserving the facial nerve. Three patients were not grafted. Most tumors (88%) affect the geniculate ganglion. Approximately 82% of the grafted patients regained a House-Brackmann facial nerve function (HB) grade III; 14% regained HB grades IV to V. No serious morbidity or mortality was reported. No recurrences have been reported where a total tumor removal was performed. Conclusion: Surgical removal of facial neuroma is a safe procedure with a low complication rate and a low recurrence rate. First symptoms are diverse and are predominantly derived from the facial and vestibulocochlear nerve. Facial nerve grafting is reliable, giving the patient an acceptable facial nerve function (HB III).

Auditory brainstem implants (ABIs) – 20 years of clinical experience in Uppsala, Sweden

Abstract Conclusions: Even though sound perception may be limited after treatment with an auditory brainstem implant (ABI), it provides benefits and should be selectively offered to patients. Importantly the patients must be motivated, given reasonable expectations of outcome and offered long-term rehabilitation with a considerable ‘learn to listen’ period with the implant device. Objectives: To describe the clinical experiences and results of 24 ABI surgeries performed in Uppsala University Hospital between 1993 and 2013. Methods: Most patients (n = 20) suffered from neurofibromatosis type 2 (NF2); a few patients (n = 4) were paediatric non-NF2 patients. The files were searched for information on the presurgery size of the vestibular schwannoma, whether the patient had undergone gamma knife treatment, the surgical approach, the side effects of the surgery and of the use of the implant, the electrode activation pattern and implant use, and categories of auditory performance (CAP) score. Results: Our results show that many patients greatly benefited from an ABI, and most of the patients used their implants even though the hearing improvements usually consisted of awareness of surrounding sounds and improved lip-reading. No severe side effects were observed from implant stimulation.

Loud Noise Exposure and Acoustic Neuroma

The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.

Consensus statement: Long-term results of ABI in children with complex inner ear malformations and decision making between CI and ABI

Consensus statement : Long-term results of ABI in children with complex inner ear malformations and decision making between CI and ABI