[Trigeminal neuralgia : Modern diagnostic workup and treatment]. / Trigeminusneuralgie : Moderne Diagnostik und Therapie.

The present article gives an update of relevant aspects in the diagnosis and therapy of trigeminal neuralgia from the neurological, neuroradiological and neurosurgical point of view. The diagnosis of trigeminal neuralgia is clinical, but high-quality imaging is mandatory to identify secondary causes and a neurovascular contact. New methods such as DTI (diffusion tensor imaging) allow a more differentiated assessment of the consequences of a vascular contact on the trigeminal nerve. Carbamazepine and oxcarbazepine continue to be first choice for the medical treatment, but have been supplemented by additional options such as pregabaline, lamotrigine, and onabotulinumtoxin A. In patients insufficiently responding to medical treatment, there are neurosurgical treatment options giving very good results. The best long-term results have been described for microvascular decompression, but percutaneous and radiosurgical treatments also are good options, especially in patients with an increased surgical risk profile, in secondary trigeminal neuralgia, and in case of recurrence after microvascular decompression.

Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses.

In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[(18)F]fluoroethyl)-1-tyrosine ((18)F-FET) positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns. Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome. (18)F-FET PET-guided biopsies were used for stepwise histopathological evaluation. Molecular-genetic evaluation included O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase (IDH1/2) mutational and 1p/19q codeletion status. Progression-free survival (PFS) was estimated with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models. 98 adult patients were included. Homogeneous increasing, focal decreasing and homogeneous decreasing TAC were seen in 51, 19 and 28 patients. The corresponding 1-year (2-years) PFS were 92% (85%), 89% (51%) and 50% (28%; p = 0.002). IDH1/2 mutations were more frequent in tumors with homogeneous increasing (90%) and focal decreasing (79%) TAC, but were rare in those exhibiting homogeneous decreasing TAC (25%; p < 0.001). Overall, TAC patterns, IDH1/2 mutational and 1p/19q codeletion status were powerful and independent prognostic factors. Dynamic (18)F-FET PET might be an important and independent imaging biomarker for patients with suspected WHO grade II gliomas and offers perspectives for stratified diagnostic and therapeutic strategies. Tumors with focal decreasing TAC need highly targeted surgical interventions to avoid undergrading and undertreatment.

Microsurgical fenestration of idiopathic intramedullary cysts in adult patients.

PURPOSE: The aim of this study is to describe the findings in one of the largest series of microsurgically treated intramedullary cysts investigated by magnetic resonance imaging (MRI), focusing on the peri- and intraoperative setup including detailed neurological and radiological outcome analyses. METHODS: Retrospective analysis of patients with intramedullary cyst who had undergone microsurgical fenestration at our department between 2006 and 2011. Preoperative three-dimensional constructive interference of steady-state MRI was conducted to optimize surgical planning. Intraoperative electrophysiological monitoring included motor-evoked potentials, somatosensory-evoked potentials, and electromyogram. Clinical outcome as well as pre-, postoperative and long-term MRI scans were evaluated. RESULTS: Eight female patients (median age 58.0 years, range 32-72 years) with a median clinical follow-up of 48.0 months (range 2-69 months) were included. Seven cysts were located in the conus medullaris, one in the cervical spine. Overall, 25.0% (2/8) showed complete remission of preoperative symptoms, 62.5% (5/8) improved, and 12.5% (1/8) asymptomatic patients remained unchanged. Pain syndromes (4/4) as well as motor deficits (2/2) improved in all affected patients and bladder dysfunction (3/4) displayed a high tendency for improvement. Postoperative MRI scans showed permanently decreased cyst volumes by ~80%. CONCLUSION: Microsurgical fenestration of intramedullary cysts using preoperative high-resolution imaging and intraoperative electrophysiological monitoring is a safe and effective treatment option for symptomatic patients.

The value of magnetic resonance imaging for the detection of the bleeding source in non-traumatic intracerebral haemorrhages: a comparison with conventional digital subtraction angiography.

INTRODUCTION: Conventional digital subtraction angiography (DSA) is currently regarded as the gold standard in detecting underlying vascular pathologies in patients with intracerebral haemorrhages (ICH). However, the use of magnetic resonance imaging (MRI) in the diagnostic workup of ICHs has considerably increased in recent years. Our aim was to evaluate the diagnostic accuracy and yield of MRI for the detection of the underlying aetiology in ICH patients. METHODS: Sixty-seven consecutive patients with an acute ICH who underwent MRI (including magnetic resonance angiography (MRA) and DSA during their diagnostic workup) were included in the study. Magnetic resonance images were retrospectively analysed by two independent neuroradiologists to determine the localisation and cause of the ICH. DSA was used as a reference standard. RESULTS: In seven patients (10.4%), a DSA-positive vascular aetiology was present (one aneurysm, four arteriovenous malformations, one dural arteriovenous fistula and one vasculitis). All of these cases were correctly diagnosed by both readers on MRI. In addition, MRI revealed the following probable bleeding causes in 39 of the 60 DSA-negative patients: cerebral amyloid angiopathy (17), cavernoma (9), arterial hypertension (8), haemorrhagic transformation of an ischaemic infarction (3) and malignant brain tumour with secondary ICH (2). CONCLUSION: Performing MRI with MRA proved to be an accurate diagnostic tool in detecting vascular malformations in patients with ICH. In addition, MRI provided valuable information regarding DSA-negative ICH causes, and thus had a high diagnostic yield in ICH patients.

Osteoarthritis of the knee at 3.0 T: comparison of a quantitative and a semi-quantitative score for the assessment of the extent of cartilage lesion and bone marrow edema pattern in a 24-month longitudinal study.

OBJECTIVE: To compare a semi-quantitative and a quantitative morphological score for assessment of early osteoarthritis (OA) evolution. MATERIALS AND METHODS: 3.0 T MRI of the knee was performed in 60 women, 30 with early OA (each 15 with Kellgren-Lawrence grade 2 and 3) and 30 age-matched controls at baseline and at 12 and 24 months. Pathological condition was assessed with the whole-organ magnetic resonance imaging score (WORMS). Cartilage abnormalities and bone marrow edema pattern (BMEP) were also quantified using a previously introduced morphological quantitative score. These data were correlated with changes in clinical parameters and joint space width using generalized estimation equations (GEE). RESULTS: At baseline, OA patients had significantly (p < 0.05) more and larger cartilage lesions and BMEP. During follow-up, cartilage lesions increased significantly (p < 0.05) in the patients compared with controls: WORMS showed progression only at the lateral patella, whereas the quantitative score revealed progression additionally at the trochlea and at the medial compartment. Both scores showed a significant (p < 0.05) increase in BMEP at the lateral femur in OA patients. In addition, quantitative scores of BMEP of the whole knee decreased significantly (p < 0.05) after 12 months and increased after 24 months in the patients, but showed an increase in controls at all follow-up examinations. Only weak correlations between structural imaging findings and clinical parameters were observed. CONCLUSION: Quantitative assessment of cartilage lesions and BMEP is more sensitive to changes during the course of the disease than semi-quantitative scoring. However, structural imaging findings do not correlate well with the clinical progression of OA.

Separating distinct aspects of the voluntary selection between response alternatives: N2- and P3-related BOLD responses.

Voluntary selection between response alternatives belongs to cognitive abilities controlling and regulating goal-directed behaviour. Voluntary selection processes are associated with increased neural activity, especially in medial and lateral frontal brain regions as well as the inferior parietal gyrus. However, the precise function of each brain region as well as the spatiotemporal characteristic of the brain regions involved is not yet clear. The aim of the present study was to disentangle distinct aspects of voluntary selection and their underlying neural processes. Hence, event-related potentials (ERPs) and functional MRI data were acquired simultaneously. Brain regions modulated by the task-induced amplitude variation of ERPs (N2, P3) were identified. The results showed N2-related hemodynamic responses, especially in medial and lateral frontal brain regions. Among other things, medial frontal brain regions are related to conflict monitoring, control of voluntary action and decision making. By contrast, the P3-amplitude proved to be predominantly related to increased BOLD responses in the temporo-parietal junction and lateral frontal brain regions. These brain regions are thought to play a decisive role in an attentional network involved in detecting auditory and visual stimuli. Overall, the results of the study indicated a whole network of brain regions to be associated with voluntary selection processes. In addition, at least some frontal brain regions seemed to be involved at an earlier stage than temporo-parietal regions, probably indicating a top-down process.

Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients.

Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.

Diffusion Tensor Imaging for Surgical Planning in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND AND STUDY AIMS/OBJECTIVE: Despite its invasiveness, computed tomography myelography (CTM) is still considered an important supplement to conventional magnetic resonance imaging (MRI) for preoperative evaluation of multilevel cervical spondylotic myelopathy (CSM). We analyzed if diffusion tensor imaging (DTI) could be a less invasive alternative for this purpose. MATERIAL AND METHODS: In 20 patients with CSM and an indication for decompression of at least one level, CTM was performed preoperatively to determine the extent of spinal canal/cerebrospinal fluid (CSF) space and cord compression (Naganawa score) for a decision on the number of levels to be decompressed. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were correlated with these parameters and with MRI-based increased signal intensity (ISI). Receiver operating characteristic analysis was performed to determine the sensitivity to discriminate levels requiring decompression surgery. European Myelopathy Score (EMS) and neck/radicular visual analog scale (VAS-N/R) were used for clinical evaluation. RESULTS: According to preoperative CTM, 20 levels of maximum and 16 levels of relevant additional stenosis were defined and decompressed. Preoperative FA and particularly ADC showed a significant correlation with the CTM Naganawa score but also with the ISI grade. Furthermore, both FA and ADC facilitated a good discrimination between stenotic and nonstenotic levels with cutoff values < 0.49 for FA and > 1.15 × 10-9 m2/s for ADC. FA and especially ADC revealed a considerably higher sensitivity (79% and 82%, respectively) in discriminating levels requiring decompression surgery compared with ISI (55%). EMS and VAS-N/R were significantly improved at 14 months compared with preoperative values. CONCLUSION: DTI parameters are highly sensitive at distinguishing surgical from nonsurgical levels in CSM patients and might therefore represent a less invasive alternative to CTM for surgical planning.

Changes of brain DTI in healthy human subjects after 520 days isolation and confinement on a simulated mission to Mars.

INTRODUCTION: Long-term confinement is known to be a stressful experience with multiple psycho-physiological effects. In the MARS500 project, a real-time simulation of a space-flight to Mars conducted in a hermetically isolated habitat, effects of long-term confinement could be investigated in a unique manner. The aim of this study was to evaluate effects of long-term-confinement on brain cytoarchitecture. MATERIAL & METHODS: The participants of the MARS500 project underwent 3T-MR imaging including a dedicated DTI-sequence before the isolation, right after ending of confinement and 6 months after the experiment. Voxelwise statistical analysis of the DTI data was carried out using tract-based-spatial statistics, comparing an age-matched control group. RESULTS: At all three sessions, significant lower fractional anisotropy (FA) than in controls was found in the anterior parts of the callosal body of the participants. Furthermore, after ending of confinement a wide-spread FA reduction could be seen in the right hemisphere culminating in the temporo-parietal-junction-zone. All these areas with decreased FA predominantly showed an elevated radial diffusivity and mean diffusivity while axial diffusivity was less correlated. DISCUSSION: Long-term confinement does have measurable effects on the microstructure of the brain white matter. We assume effects of sensory deprivation to account for the regional FA reductions seen in the right TPJ. The differences in the Corpus callosum were interpreted as due to preliminary conditions, e.g. personality traits or training effects. FA and radial diffusivity were the predominant DTI parameters with significant changes, suggesting underlying processes of myelin plasticity.

The free choice whether or not to respond after stimulus presentation.

The concept of 'willed' actions has attracted attention during the last few years. Free choices have been associated with activations on the medial frontal surface, the dorsolateral prefrontal cortex and the parietal lobe. Self-paced movements and free selection between various motor responses were typically used to investigate voluntary behavior. The aim of the present study was to determine neural correlates of voluntary motor responses and the voluntary inhibition of motor responses in a group of healthy subjects. Hence, a go/nogo/voluntary selection paradigm was used. In the voluntary selection condition subjects decided freely whether or not to respond with a button press after stimulus presentation. Functional MRI data and event-related potentials were acquired simultaneously in order to reliably investigate spatial and temporal characteristics of these responses. The results showed decision-related enhanced neural responses predominantly in the medial frontal gyrus/supplementary motor area, lateral frontal brain regions and the inferior parietal gyrus. Additional activations associated with voluntary movements were detected in the frontal eye field as well as brain regions directly linked to motor responses (e.g. somatosensory cortical areas). Altogether, decision processes were shown to be relatively independent of the kind of response chosen.

Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers.

Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only a few studies investigated the brain activation patterns following CCK-4, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. We studied the functional correlates of CCK-4-induced anxiety in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with placebo in a single-blind design. Functional brain activation patterns were determined for the CCK-4-challenge, the placebo response and anticipatory anxiety (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus, precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas, cerebellum, and brainstem. In contrast, random effects group analysis for placebo and AA using the same level of significance generated no significant results. Using a more liberal level of significance, activations could be observed in some brain regions such as the dorsal part of the ACC during AA (random effects analysis, P < 0.005). Overall functional responses did not differ between panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala activation. However, ROI analysis pointed towards higher scores in fear items in these subjects. In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4-induced fear.

Measurement of structural integrity of the spinal cord in patients with amyotrophic lateral sclerosis using diffusion tensor magnetic resonance imaging.

BACKGROUND: The value of conventional magnetic resonance imaging (MRI) for amyotrophic lateral sclerosis (ALS) is low. Functional and quantitative MRI could be more accurate. We aimed to examine the value of diffusion tensor imaging (DTI) with fractional anisotropy (FA) measurements of the cervical and upper thoracic spinal cord in patients with ALS. PATIENTS AND METHODS: Fourteen patients with ALS and 15 sex- and age-matched controls were examined with DTI at a 3T MRI scanner. Region-of-interest (ROI) based fractional anisotropy measurements were performed at the levels C2-C4, C5-C7 and Th1-Th3. ROIs were placed at different anatomical locations of the axial cross sections of the spinal cord. RESULTS: FA was significantly reduced in ALS patients in anterolateral ROIs and the whole cross section at the C2-C4 level and the cross section of the Th1-Th3 level. There was a trend towards a statistically significant FA reduction in the anterolateral ROIs at the C5-C7 level in ALS patients. No significant differences between patients and controls were found in posterior ROIs. CONCLUSION: FA was reduced in ROIs representing the motor tracts in ALS patients. DTI with FA measurements is a promising method in this circumstance. However, for DTI to become a valuable and established method in the diagnostic workup of ALS, larger studies and further standardisation are warranted.

Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making.

While the precise role of the anterior cingulate cortex (ACC) is still being discussed, it has been suggested that ACC activity might reflect the amount of mental effort associated with cognitive processing. So far, not much is known about the temporal dynamics of ACC activity in effort-related decision making or auditory attention, because fMRI is limited concerning its temporal resolution and electroencephalography (EEG) is limited concerning its spatial resolution. Single-trial coupling of EEG and fMRI can be used to predict the BOLD signal specifically related to amplitude variations of electrophysiological components. The striking feature of single-trial coupling is its ability to separate different aspects of the BOLD signal according to their specific relationship to a distinct neural process. In the present study we investigated 10 healthy subjects with a forced choice reaction task under both low and high effort conditions and a control condition (passive listening) using simultaneous EEG and fMRI. We detected a significant effect of mental effort only for the N1 potential, but not for the P300 potential. In the fMRI analysis, ACC activation was present only in the high effort condition. We used single-trial coupling of EEG and fMRI in order to separate information specific to N1-amplitude variations from the unrelated BOLD response. Under high effort conditions we were able to detect circumscribed BOLD activations specific to the N1 potential in the ACC (t=4.7) and the auditory cortex (t=6.1). Comparing the N1-specific BOLD activity of the high effort condition versus the control condition we found only activation of the ACC (random effects analysis, corrected for multiple comparisons, t=4.4). These findings suggest a role of early ACC activation in effort-related decision making and provide a direct link between the N1 component and its corresponding BOLD signal.

Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses.

Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.

Outcome in unresectable glioblastoma: MGMT promoter methylation makes the difference.

In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ â†’ TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ â†’ TMZ treatment between March 2006 and August 2008. Last follow-up was performed in June 2016. MGMT promoter methylation was determined using methylation-specific PCR (MSP) and sodium bisulfite sequencing. Analyses were done by intention to treat. Prognostic factors were obtained from proportional hazard models. At the time of the final analysis 55 patients showed progressive disease and 53 patients had died. MGMT promoter was methylated (unmethylated) in 30 (26) patients. Methylation of the MGMT promoter was the strongest favorable predictor for overall survival (OS, median: 20.3 vs. 7.3 months, p < 0.001, HR 0.30, 95% CI 0.16-0.55), and PFS (median: 15.0 vs. 6.1 months, p < 0.001, HR 0.31, 95% CI 0.17-0.57) and was also associated with higher frequencies of treatment response and prolonged post-recurrence survival (PRS, median: 4.5 vs. 1.4 months, p < 0.002, HR 0.39, 95% CI 0.21-0.71). Knowledge of MGMT promoter methylation status is essential for patients' counseling, prognostic evaluation, and for the design of future trials dealing with unresectable glioblastomas.

Discontinuous patterns of brain activation in the psychotherapy process of obsessive-compulsive disorder: converging results from repeated FMRI and daily self-reports.

This study investigates neuronal activation patterns during the psychotherapeutic process, assuming that change dynamics undergo critical instabilities and discontinuous transitions. An internet-based system was used to collect daily self-assessments during inpatient therapies. A dynamic complexity measure was applied to the resulting time series. Critical phases of the change process were indicated by the maxima of the varying complexity. Repeated functional magnetic resonance imaging (fMRI) measurements were conducted over the course of the therapy. The study was realized with 9 patients suffering from obsessive-compulsive disorder (subtype: washing/contamination fear) and 9 matched healthy controls. For symptom-provocative stimulation individualized pictures from patients' personal environments were used. The neuronal responses to these disease-specific pictures were compared to the responses during standardized disgust-provoking and neutral pictures. Considerably larger neuronal changes in therapy-relevant brain areas (cingulate cortex/supplementary motor cortex, bilateral dorsolateral prefrontal cortex, bilateral insula, bilateral parietal cortex, cuneus) were observed during critical phases (order transitions), as compared to non-critical phases, and also compared to healthy controls. The data indicate that non-stationary changes play a crucial role in the psychotherapeutic process supporting self-organization and complexity models of therapeutic change.

Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [(18)F]FET-PET imaging in intracranial WHO grade II and III gliomas.

Oligodendroglial components (OC) and loss of heterozygosity on chromosomes 1p and 19q (LOH 1p/19q) are associated with better outcome in patients with glioma. We aimed to assess the fitness of [(18)F]fluoroethyltyrosine positron-emission-tomography (FET-PET) for noninvasively identifying these important prognostic/predictive factors. One hundred forty-four patients with MRI-suspected WHO grade II and III glioma underwent FET-PET scans prior to histological diagnosis. FET-PET analyses included maximal tumoral uptake (SUV(max)/BG), biological tumor volume (BTV), mean tumoral uptake (SUV(mean)/BG), total tumoral uptake (SUV(total)/BG), and kinetic analysis. Suspicion of OC was based on static and dynamic FET-uptake parameters. PET results were correlated with histology and 1p/19q status. OC tumors exhibited significantly higher uptake values, compared with astrocytomas (AC) (SUV(max)/BG 3.1 vs 2.3, BTV 15.5 mL vs 7.2 mL, SUV(total)/BG 38.5 vs 17.4, P < .01 each; SUV(mean)/BG 2.2 vs 2.1, P < .05). These differences were more pronounced in WHO grade II gliomas. Comparable results were found with respect to 1p/19q status. Kinetic analysis misclassified 18 of 34 low-grade OC tumors as high-grade glioma but misclassified only 5 of 45 of the low-grade ACs. FET-based suspicion of OC resulted in concordance rates of both 76% for the prediction of OC and LOH 1p/19q. FET-uptake was significantly higher in gliomas with OC, compared with AC, and likewise in 1p/19q codeleted, compared with noncodeleted tumors. However, FET-PET analysis did not reliably predict the presence of OC/LOH 1p/19q in the individual patient, mostly because of an overlap in PET characteristics of OC tumors and high-grade AC. Histological examination is still required for an accurate diagnosis.

Prevalence of pathologic findings in the maxillary sinus in cone-beam computerized tomography.

OBJECTIVE: The aim of this study was to assess the prevalence of pathologic findings in the maxillary sinus by using cone-beam computerized tomography (CBCT). STUDY DESIGN: One thousand twenty-nine consecutive CBCT scans were retrospectively inspected for pathologic findings in the maxillary sinus by 3 observers. Findings were differentiated by mucosal thickening, partial opacification with liquid accumulation, total opacification, and polypoidal mucosal thickening. Position and diameter of the maxillary sinus ostium were assessed. Correlations for pathologic findings and the factors of age and gender were calculated. Patients with clinical manifestations of sinusitis or total opacification in either sinus were reevaluated. RESULTS: A total prevalence for pathologies in the maxillary sinus of 56.3% was found in this study. The most frequent pathology was mucosal thickening. Patients >60 years of age showed significantly more pathologies in the maxillary sinus (P = .02), and male patients showed significantly more pathologies than female patients (P = .01). Clinical signs of sinusitis could be confirmed on CBCT images for all patients. CONCLUSIONS: Pathologies in the maxillary sinus are frequently found in CBCT imaging and have to be treated or followed-up accordingly. CBCT is applicable for diagnosis and treatment planning of clinically present sinusitis.

The characterization of Lucilia cuprina acetylcholinesterase as a drug target, and the identification of novel inhibitors by high throughput screening.

Acetylcholinesterase (AChE, EC3.1.1.7.) is the molecular target for the carbamate and organophosphate pesticides that are used to combat parasitic arthropods. In this paper we report the functional heterologous expression of AChE from Lucilia cuprina (the sheep blowfly) in HEK293 cells. We show that the expressed enzyme is cell-surface-exposed and possesses a glycosyl-phosphatidylinositol membrane anchor. The substrates acetyl-, propionyl- and butyrylthiocholine (AcTC, PropTC, ButTC), and also 11 further thiocholine and homo-thiocholine derivatives were chemically synthesized to evaluate and compare their substrate properties in L. cuprina AChE and recombinant human AChE. The Michaelis-Menten constants K(M) for AcTC, PropTC and ButTC were found to be 3-7-fold lower for the L. cuprina AChE than for the human AChE. Additionally, 2-methoxyacetyl-thiocholine and isobutyryl-thiocholine were better substrates for the insect enzyme than for the human AChE. The AcTC, PropTC and ButTC specificities and the Michaelis-Menten constants for recombinant L. cuprina AChE were similar to those determined for AChE extracted from L. cuprina heads, which are a particularly rich source of this enzyme. The median inhibition concentrations (IC(50) values) were determined for 21 organophosphates, 23 carbamates and also 9 known non-covalent AChE inhibitors. Interestingly, 11 compounds were 100- to >4000-fold more active on the insect enzyme than on the human enzyme. The substrate and inhibitor selectivity data collectively indicate that there are structural differences between L. cuprina and human AChE in or near the active sites, suggesting that it may be possible to identify novel, specific L. cuprina AChE inhibitors. To this end, a high throughput screen with 107,893 compounds was performed on the L. cuprina head AChE. This led to the identification of 195 non-carbamate, non-organophosphate inhibitors with IC(50) values below 10µM. Analysis of the most potent hit compounds identified 19 previously unknown inhibitors with IC(50) values below 200nM, which were up to 335-fold more potent on the L. cuprina enzyme than on the human AChE. Some of these compounds may serve as leads for lead optimization programs to generate fly-specific pesticides.