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O Sabri

Publications and source records attributed to O Sabri.

At least 19 recordsLinked to original sources
PubMed2006

Profound midbrain atrophy in patients with Wilson's disease and neurological symptoms?

Wilson's disease (WD) is characterized by impaired hepatic copper secretion and subsequent copper accumulation in many organs predominantly liver and brain, secondary to loss of function mutations in the copper transport protein ATP7B. If the disease is recognized too late or treatment is not adequate, brain copper accumulation leads to progressive neurodegeneration with a variety of clinical symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain atrophy, however, has not been recognized as one of the prime features of patients with WD. Here we report quantification of midbrain diameter in 41 patients with WD. Data were correlated to the severity of neurological symptoms and the integrity of dopaminergic neurons measured via dopamine transporter binding. For control, we measured midbrain diameter in 18 patients with no evidence for brainstem dysfunction and 5 patients with progressive supranuclear palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 +/- 0.4 mm) compared to controls (18.5 +/- 0.2 mm). WD patients without neurological symptoms had midbrain diameter that were not different from controls (18.0 +/- 0.3 mm), while patients with neurological symptoms showed midbrain atrophy similar to patients with PSP (14.4 +/- 0.3 mm versus 14.1 +/- 0.3). There was a strong and significant correlation between midbrain atrophy and the severity of neurological symptoms (r= -0.68, p < 0.001) while midbrain atrophy and dopamine transporter binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In summary, we were able to show, that midbrain diameter is an easy to perform quantification of neurodegeneration induced by brain copper accumulation and that other structures than substantia nigra dopaminergic neurons seem to contribute to midbrain atrophy in WD.

Adult↗
PubMed2006

Possible impact of dopamine SPECT on decision-making for drug treatment in Parkinsonian syndrome.

Single-photon emission computed tomography (SPECT) markers allow measuring the integrity of the brain dopaminergic system in vivo. We used dopamine transporter (DAT) SPECT with [(123)I]FP-CIT and dopamine D(2)/D(3) receptor SPECT with [(123)I]IBZM to evaluate whether there is a reduction of DAT and/or D(2)/D(3) receptor SPECT in treated and untreated patients with Parkinsonian syndrome (PS). We found that almost a quarter of our patients treated with anti-Parkinsonian medication prior to SPECT imaging did not show evidence of a presynaptic dopaminergic deficit while 37% of untreated patients were diagnosed as having Parkinson's disease. 17% of treated patients had additional loss of D(2)/D(3) receptor binding capacity in concordance with the clinical follow-up diagnoses of multiple system atrophy, progressive nuclear palsy, and vascular Parkinsonism. Apart from 38% clinically uncertain cases, SPECT was in concordance with 75% of initial clinical diagnoses. 25% were reclassified as indicated by SPECT findings and confirmed by a 1.5-year clinical follow-up. We conclude that dopamine SPECT may support establishing or refuting the clinical diagnosis and, therefore, help to make the decision for or against dopaminomimetic treatment in cases with PS.

Aged↗
PubMed2006

Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients.

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc-99m-ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients' history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural-, or functional neuroimaging, nor by the patient-specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials.

Adult↗
PubMed2005

[Is 18F-FDG-PET suitable for therapy monitoring after palliative photodynamic therapy of non-resectable hilar cholangiocarcinoma?].

BACKGROUND: If existing biliary drainage is insufficient, photodynamic therapy (PDT, laser treatment after application of a photosensitizer) is an already established adjunct to palliative therapy for progressing hilar cholangiocarcinoma (Klatskin tumours), since it prolongs survival and improves quality of life. Experimental studies of other tumour entities showed that (18)F-FDG-PET ( (18)F-fluorodeosxyglucose-positron emission tomography) may play a role in monitoring tumour response to PDT. Furthermore, previous studies have revealed a high accuracy of this method for the detection of hilar cholangiocarcinoma. Therefore, the aim of the present study was to investigate the feasibility of (18)F-FDG-PET as a follow-up screening method in patients with hilar cholangiocarcinoma who underwent PDT. PATIENTS AND METHODS: 10 patients were examined by (18)F-FDG-PET before and 4 - 6 weeks after PDT. The following parameters were evaluated: maximum and mean SUV in the tumour, the ratio of maximum SUV in the tumour and mean SUV in the liver, the vital tumour volume, as well as bilirubin and CA 19 - 9 levels. RESULTS: All tumours were detected by (18)F-FDG-PET. Within a period of 4 - 6 weeks after PDT the cholestasis parameter bilirubin decreased significantly. However, SUV-associated parameters did not show a significant change after treatment while the estimated vital tumour volume even increased. DISCUSSION: PDT does not effect a relevant reduction of tumour mass in non-resectable hilar cholangiocarcinoma. However, PDT leads to a significant reduction of cholestasis. If (18)F-FDG-PET is suitable for monitoring the effect of new palliative therapeutic approaches, like brachytherapy, the use of modern chemotherapeuticals, COX-2 and receptor-tyrosine kinase inhibitors, perhaps also in combination with PDT, has to be further investigated.

Bile Duct Neoplasms↗
PubMed2005

D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients.

RATIONALE: A relationship between high D2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuroimaging studies. OBJECTIVES: We investigated the striatal dopamine D2 receptor occupancy, risperidone plasma level and extrapyramidal-motor symptoms in drug-free schizophrenic patients. METHODS: Ten schizophrenic patients were treated with 3 - 6 mg risperidone daily. After four weeks administration, a [(123)I]iodobenzamide ([(123)I]IBZM)-single photon emission tomography (SPET) scan for determination of D2 receptor occupancy was carried out (in eight responders) and compared to a control group. Plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (active moiety) were determined by high performance liquid chromatography and electrochemical detection. Extrapyramidal-motor symptoms were assessed by means of the Simpson-Angus-Scale and a handwriting test before treatment and coincident with the scan. RESULTS: The D2 receptor occupancy (Mean 62%, SD 13%) positively correlated with the plasma level of the risperidone active moiety as well as with the reduction in handwriting area. Multiple linear regression revealed an inherent relationship with a coefficient of determination of r = 0.956 (p = 0.02). No clinical relevant extrapyramidal-motor symptoms were observed. CONCLUSIONS: In drug-free schizophrenic responders, the simultaneous assessment of both plasma level and reduction in handwriting area may be a useful clinical tool for a surrogate estimate of D2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms.

Adult↗
PubMed2004

[Preoperative imaging as the basis for image-guided neurosurgery].

With the progressive development of soft- and hardware, the acceptance of image-guided neurosurgery has increased dramatically. Additional image data are required to analyze the nature and the dimensions of pathological processes and the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special modalities of CT and MR imaging, are routinely used. Secondary post-processing options are used to detect intracerebral lesions as well as adjacent functional eloquent regions in the parenchymatous organ pre- and intraoperatively. The integration of different image information guarantees the precise planning and realization of surgical maneuvers. The segmentation of interesting structures and risk structures, as well as their implementation in the neuronavigation systems, help to avoid additional intraoperative traumatization and offer a higher level of safety and precision. In this article the value and limitations of presurgical imaging will be discussed.

Brain↗
PubMed2004

MRI-based individual 3D region-of-interest atlases of the human brain: a new method for analyzing functional data.

OBJECTIVES: Introduction of a new atlas-based method for analyzing functional data which takes into account the variability of individual human brains and the partial volume, effects of functional emission computed tomography, images in complex anatomical 3D regions, as well as, describing the underlying multi-modal image processing, principles. METHODS: 3D atlas extraction is done directly by automated segmentation of individual magnetic resonance images of the patient's head. This is done in two steps: voxel-based classification of T1-weighted images for tissue differentiation (low-level processing) is followed by knowledge-based analysis of the classified images for extraction of 3D anatomical regions (high-level processing). For atlas-based quantification of co-registered functional images, 3D anatomical regions can be convoluted with an idealized point spread function of the emission computed tomography system, after which a partial volume-dependent threshold can be determined. RESULTS: Quantitative evaluation studies, based on 50 realistic software head phantoms and 24 image data sets obtained from healthy subjects and patients, show low misclassification rates and stable results for the neural network-based classification approach (mean +/- SD 3.587 +/- 0.466%, range 2.726-4.927%) as well as for the adjustable parameters of the knowledge-based approach. Computation time is <5 min for classification, <1 min for most of the extraction algorithms. The influence of the partial volume-dependent threshold is shown for an activation study. CONCLUSIONS: This new method allows 3D atlas generation without the need to warp individual image data to an anatomical or statistical brain atlas. Going beyond the purely tissue-oriented approach, partial volume effects of emission computed tomography images can be analyzed in complex anatomical 3D regions.

Algorithms↗
PubMed2003

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease.

OBJECTIVE: One of the most frequent psychiatric symptoms in patients with Wilson's disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. METHODS: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus-hypothalamus and the midbrain-pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2beta-carbomethoxy-3beta-(4 [(123)I]iodophenyl)tropane ( [(123)I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. RESULTS: A significant negative correlation was found between HAMD and SERT density in the thalamus-hypothalamus region (r = -0.49, p = 0.02), but not in the midbrain-pons (r = -0.31, p = 0.15). CONCLUSIONS: We conclude that depression in patients with Wilson's disease is correlated with alterations of serotonergic neurotransmission in the thalamus-hypothalamus region.

Adult↗
PubMed2003

Regional serotonin transporter availability and depression are correlated in Wilson's disease.

In patients with Wilson's disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [123I]-2beta-carbomethoxy-3beta-(iodophenyl)tropane ([123I]beta-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [123I]beta-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients.

Adult↗
PubMed2003

In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.

The radiolabeled serotonin transporter (SERT) ligand [(11)C](+)-McN5652 has recently been used in clinical positron emission tomography (PET) studies for SERT imaging. However, this radioligand offers disadvantages in routine clinical settings because of its short radioisotope half-life (eg PET facilities within hospitals without a cyclotron need to acquire such radioligands from distant cyclotron units for clinical use). S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-FMe-McN5652) is an analogue which has been synthesized newly, and has a significantly longer radioisotope half-life. In the porcine brain, it demonstrates the same characteristic distribution pattern of serotonin-uptake sites like the (11)C-labeled congener with the highest binding in the midbrain and thalamus and the lowest in the cerebellum and occipital cortex. It shows a 30% higher blood-brain transfer and a slower peripheral metabolism than [(11)C](+)-McN5652. Rather uniform brain binding was observed after injection of the pharmacologically inactive radiolabeled enantiomer, or after pretreatment with the highly selective SERT inhibitor citalopram. The norepinephrine uptake inhibitor maprotiline did not show any inhibitory effect. Using a one-tissue compartment model (K(1), k"(2)) or a two-tissue compartment model (K(1) to k(4)) with or without constraints for calculation, the regional binding parameters of [(11)C](+)-McN5652 and [(18)F](+)-FMe-McN5652 are highly correlated among each other and with the SERT density, as determined by in vitro binding of [(3)H]citalopram. Using constraints to correct for the free fraction and nonspecific binding of the radiotracers, a considerable increase of the midbrain-occipital cortex ratios with higher values for [(18)F](+)-FMe-McN5652 compared to [(11)C](+)McN5652 was revealed. It is concluded that [(18)F](+)-FMe-McN5652 has better features than [(11)C](+)McN5652 for SERT imaging with PET.

Animals↗
PubMed2003

Radioiodine therapy in patients with hyperthyroid disorder: standard versus dosimetric activity application.

Due to its high success rate and non-invasive character, an increasing demand for radioiodine therapy can be seen. This study was conducted to determine whether standardized 131I activities can be used to facilitate management of patients with hyperthyroid disorder or whether a pre-therapeutic radioiodine test is advisable to determine an adequate therapeutic activity. The therapeutic uptake of 218 patients with benign thyroid disorders were determined and compared with 24 h and 48 h test uptake measurements as well as with calculated standard uptake values. Since there is a linear relationship between iodine uptake and delivered radiation dose, the effect of the different therapeutic approaches on the latter parameter was analysed. Special care was taken to assess possible differences between the various thyroid disorders. A mean deviation between pre-therapeutic test uptake and actual therapeutic uptake of 14.7% was observed in contrast to one of 29.1% when using disease specific standard values per millilitre of thyroid tissue. Furthermore, the proportion of patients with large deviations of more than 40% increased drastically when using standard uptake values (with radioiodine test, 4.1%; with standard values, 18.8%). In conclusion, the dosimetric approach with a pre-therapeutic radioiodine test proved to be the most accurate therapeutic procedure. Both the 24 h and 48 h test uptake measurements gave analogous results and yielded a correlation coefficient of 0.91 when compared with the therapeutic uptake. While it may be tempting to use standard activities to facilitate patient management, the findings of this study confirm that, for precise therapy planning, a pre-therapeutic radioiodine test is advised. Since no significant difference could be found between the 24 h and 48 h test uptake values, an early measurement 24 h after administration of the test activity is recommended.

Female↗
PubMed2003

Preoperative motor system brain mapping using positron emission tomography and statistical parametric mapping: hints on cortical reorganisation.

OBJECTIVES: This study investigated the applicability of statistical parametric mapping (SPM) for analysing individual preoperative brain mapping studies in patients with cerebral mass lesions for neurosurgical planning. The study further investigated if hints on functional reorganisation processes can be found. METHODS: Nine adult patients with cerebral mass lesions underwent activation [(15)O]water-PET under stimulation by finger (n=9) and foot (n=4) movement. Individual SPM-t-maps were computed without anatomical normalisation and coregistered to the individual magnetic resonance imaging. Relative cerebral blood flow change maps were calculated for comparison. RESULTS: The spatial relation between the sensorimotor cortex and the lesion could be determined in all cases. Additional activations covered the ipsilateral sensorimotor cortex and the bilateral cerebellum, premotor cortices and supplementary motor areas. Patients with motor symptoms of the stimulated hand (paresis, focal seizures) activated the ipsilateral premotor cortices and contralateral cerebellum more often than patients without motor symptoms. The SPM results for p<0.005 and cerebral blood flow change maps showed considerably overlapping motor area activations. For p<0.001, SPM missed three sensorimotor cortex activations depicted by cerebral blood flow change maps and by SPM for p<0.005 in typical localisation. SPM analyses showed less activations probably unrelated to task performance. CONCLUSION: It is concluded that SPM provides an efficient method for analysing individual preoperative PET activation studies. Activations of the ipsilateral premotor cortices and contralateral cerebellum may indicate an enhanced recruitment of ipsilateral motor pathways evoked by functional reorganisation processes. However, this changed activation pattern was not necessarily associated with a better neurological status.

Adult↗
PubMed2003

Importance of F18-fluorodeoxy-D-2-glucose positron emission tomography (FDG-PET) for staging and therapy control of Hodgkin's lymphoma in childhood and adolescence - consequences for the GPOH-HD 2003 protocol.

The prognosis for children and adolescents with Hodgkin's lymphoma is excellent. However, many patients will show secondary malignancies 15-30 years after the initial diagnosis, which appears to be connected with the intensity of treatment during primary disease. In the GPOH-HD 95 trial, the indication for radiotherapy was limited to patients who did not show a complete remission after chemotherapy, as determined radiographically. In the future protocol, the indication for radiotherapy in patients with early-stage Hodgkin's lymphoma should be further refined by using FDG-PET for evaluating the response to chemotherapy. Furthermore, in patients at an advanced stage of the disease, it should be determined if sequential FDG-PET research during chemotherapy can separate patients into subgroups with an excellent or a poor prognosis. This article gives a review of the current literature on FDG-PET in patients with Hodgkin's lymphoma and outlines the consequences for future protocols.

Adolescent↗
PubMed2003

Two somatic TSH receptor mutations in a patient with toxic metastasising follicular thyroid carcinoma and non-functional lung metastases.

In a 59-year-old patient, thyroid follicular cancer was diagnosed in two right-sided toxic thyroid nodules, which had presented clinically as unilateral thyroid autonomy. In addition, the patient had histologically proven lung metastases of thyroid cancer; however, these failed to exhibit iodine uptake and were resistant to radioiodine treatment. The functional activity of the thyroid nodules prompted us to screen for TSH receptor (TSHR) mutations, and the histological diagnosis of follicular carcinoma led us to search for the PAX8-PPARgamma1 rearrangement and mutations in the ras genes. Each thyroid nodule harboured a different TSHR mutation (large nodule, Asp633Tyr; small nodule, Phe631Ile). Presence of both mutations in one sample suggestive of local invasion of a thyroid carcinoma could not be demonstrated, although several specimens from different nodule locations were screened. Only the wild-type TSHR sequence was identified in the histologically normal left thyroid lobe, and no genetic alterations were found in the other investigated genes. No TSHR mutations were detected in the pulmonary metastases. This is the first case report of a patient with toxic follicular thyroid carcinoma harbouring two different TSHR mutations and presenting with non-functional lung metastases.

Adenocarcinoma, Follicular↗