Safety and Efficacy of Calcipotriene Plus Betamethasone Dipropionate Topical Suspension in the Treatment of Extensive Scalp Psoriasis in Adolescents Ages 12 to 17 Years

The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open‐label, 8‐week study, adolescents with psoriasis (ages 12–17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once‐daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic–pituitary–adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator‐assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow‐up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once‐daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.     

Visualisation of intracerebral haemorrhage with flat-detector CT compared to multislice CT: results in 44 cases

The aim of the study was to test the reliability of intracerebral haemorrhage (ICH) detection with C-arm-mounted flat-detector computed tomography (FD-CT) in the angio suite as compared to multislice CT (MSCT). In this study 44 patients with 45 ICH were included. All patients were investigated with MSCT and FD-CT during angiographic evaluation. As a control group we included 16 patients without ICH. In each haematoma we assessed volumetric data of the ICH and counted the numbers of ICH-positive slices. Using interobserver ratings, we additionally investigated the potential of FD-CT to serve as a diagnostic tool to detect ICH. In FD-CT three haematomas were not detected because of motion and beam-hardening artefacts in the region close to the skull base. The r value for the degree of interobserver agreement for the number of slices was 0.95 for MSCT and 0.94 for FD-CT. Measurements of the area and the calculated volume of the ICH showed high inter- and intraobserver agreement. Our results indicate that FD-CT is a helpful tool in the daily emergency management of ICH patients as detection of ICH was found to be nearly as reliable as in MSCT. Limitations of this technology are motion and beam-hardening artefacts that may mask small haematomas located in the posterior fossa or the skull base.     

Influence of size of regions of interest on PET evaluation of caudate glucose consumption.

The aim of this study was to analyze the influence of variations in the size of regions of interest (ROIs) on values of caudate glucose consumption [regional cerebral metabolic rate of glucose (rCMRglc)] assessed by PET. In addition, we tried to establish the influence of ROI size on levels of significance assessing differences in mean caudate glucose consumption between two groups of subjects. For this purpose, rCMRglc was measured using [18F]fluorodeoxyglucose and the PC-4096 PET camera with an in-plane resolution of 7.1 mm in 12 normal subjects and 12 subjects with early Huntington disease. Caudate rCMRglc was histographically determined using 10 different ROI widths ranging from 2 mm, corresponding to the peak value of caudate rCM-Rglc, to 20 mm. The increase in ROI width from 2 to 20 mm led to a significant decrease of caudate rCMRglc by approximately 66% in the normal subjects and in the patients. The Student t value assessing the differences in mean caudate rCMRglc between the two groups decreased gradually from 5.61 for an ROI width of 2 mm to 3.78 for an ROI width of 20 mm. This corresponds to a worsening of the level of significance from 10(-5) to 10(-3), i.e., by a factor of 100. These data show that (given the resolution of presently used PET cameras) the selection of peak values of caudate rCMRglc is the best way to discriminate between groups of subjects supposed to differ with respect to caudate rCMRglc.     

Observation of unaveraged giant MEG activity from language areas during speech tasks in patients harboring brain lesions very close to essential language areas: expression of brain plasticity in language processing networks?

We describe a series of 12 patients who suffered from lesions adjacent to the classic Broca and Wernicke areas and were examined by magnetoencephalography (MEG) for presurgical language localization while performing a protocol of different language tasks. In these patients very large MEG activity of up to 5pT was observed, which was located not only in the adjacent language processing brain areas but also in more distant areas, which are part of the language processing neuronal network. The high amplitude and the focal spatial extent of this activity allowed MEG source localization from the unaveraged data. In nine patients sources of this high amplitude activity were even found in the homologous language areas on the contralateral, the nondominant side of the brain. The physiological interrelationship of these large MEG changes needs to be investigated in more detail in further studies especially in the context of possible mechanisms for brain plasticity to overcome inhibitory activity of the impaired language area.     

Radiosurgery of Small Skull-Base Lesions

BACKGROUND AND PURPOSE: Intensity-modulated stereotactic radiotherapy (IMSRT) has shown the ability to conform the dose to concavities and to better avoid critical organs for large tumors. Given the availability of an electronically driven micro-multileaf collimator, both intensity-modulated stereotactic radiosurgery (IMSRS) and dynamic conformal arc (DCA) technique (DCA) can be performed at the Novalis Shaped Beam Surgery Center, University of Erlangen-Nuremberg, Germany, since 12/2002. This study evaluates both techniques in small skull-base tumors treated with radiosurgery. MATERIAL AND METHODS: Between 12/2002 and 04/2004, a total of 109 radiosurgical procedures were performed in 77 patients, equally distributed between patients with acoustic neuroma (AN), pituitary adenoma (PA) and meningeoma (M). Six index patients (n = 2 AN, n = 1 PA, n = 3 M) routinely planned for dynamic arc stereotactic radiosurgery were replanned using the IMSRS approach (BrainScan, BrainLAB, Heimstetten, Germany). The RTOG radiosurgery quality assurance guidelines, isodose volumes, doses to organs at risk (OAR), and dose delivery criteria were compared. RESULTS: DCA was superior to IMSRS for homogeneity and coverage. IMSRS could keep the high-dose-irradiated volumes (90% isodose volume) lower than DCA in the PA and AN with very small volumes, but all other lower dose volumes were larger for IMSRS. Dose maxima to OAR were higher for IMSRS. Treatment delivery time for IMSRS would clearly exceed treatment time for DCA by a factor of 2-3. The integral absorbed dose to the brain was much higher in the IMSRS than in the DCA approach (factor 2-3). CONCLUSION: RTOG radiosurgery guidelines were best met by the DCA rather than IMSRS approach for the treatment of small skull-base lesions. The IMSRS approach will increase the time for planning, dose delivery and integral dose to the brain. Thus, IMSRT techniques are recommended for fractionated stereotactic radiotherapy to larger volumes rather than for radiosurgery in small skull-base lesions.     

Application accuracy of automatic registration in frameless stereotaxy

OBJECTIVE: We compared the application accuracy of an infrared-based neuronavigation system when used with a novel automatic registration with its application accuracy when standard fiducial-based registration is performed. METHODS: The automatic referencing tool is based on markers that are integrated in the headrest holder we routinely use in our intraoperative magnetic resonance imaging (MRI) setting and can be detected by the navigation software automatically. For navigation targeting we used a Plexiglas phantom with 32 notched rods of different heights. The phantom was fixed in the head holder and multiple optimized gradient echo slices containing the clamp-integrated markers were acquired. After that we measured a T1 MPRAGE sequence with a slice thickness of 1.0 mm for navigation. The deepest points of the surface of the rods were defined as target points in image space. In three measurement series we referenced the phantom once with 4, once with 7 fiducials and twice automatically. In one series we performed only one automatic registration. The localization error was measured 3 times per rod and registration. RESULTS: The median localization errors for standard registration with 7 fiducials were between 1.2 and 3.05 mm. With 4 fiducials, medians were in the range from 1.87 to 2.21 mm. For the automatic registration we obtained median localization errors between 0.88 and 2.13 mm. In 6 of the 8 samples that were compared the automatic registration showed an application accuracy that was highly significantly better (p < 0.001 in most cases) than that of fiducial-based standard registration. CONCLUSION: The application accuracy found for automatic referencing is at least not worse than that for standard registration no matter whether 4 or 7 fiducial markers were used. Therefore, its use in the operating room is feasible. In combination with intraoperative MRI it may become a favorable alternative to standard fiducial-based registration especially when an intraoperative update of navigation data is necessary.     

New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography.

We used a current localization by spatial filtering-technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke-Geschwind model. In three cases, however, we also found early Broca activation indicating that speech-related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech-related brain areas in individuals, investigating the time-course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients.     

Intraoperative compensation for brain shift.

BACKGROUND: Tumor removal, brain swelling, the use of brain retractors, and cerebrospinal-fluid drainage all result in an intraoperative brain deformation that is known as brain shift. Thus, neuronavigation systems relying on preoperative image data have a decreasing accuracy during the surgical procedure. Intraoperative image data represent the correct anatomic situation, so their use may compensate for the effects of brain shift. METHODS: In a series of 16 brain tumor patients, we used intraoperative magnetic resonance (MR) imaging to obtain 3-D data, which were then transferred to the microscope-based neuronavigation system. With the help of bone fiducial markers these images were registered intraoperatively, updating the neuronavigation system. RESULTS: In all patients the updating of the neuronavigation system with the intraoperative MR data was successful. It led to reliable neuronavigation with high accuracy; the mean registration error of the update procedure in all patients was 1.1 mm. The updating procedure added about 15 minutes to the operation time. In all patients the area suggestive of remaining tumor was reached and the additional tumor could be resected, resulting in a complete tumor removal in 14 patients. In the remaining patients extension of the tumor into eloquent brain areas prevented a complete excision. CONCLUSIONS: The update of a neuronavigation system with intraoperative MR images reliably compensates for the effects of brain shift. This method allows completion of tumor removal in some difficult brain tumors.