Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

Added value of FDG-PET for detection of progressive supranuclear palsy.

BACKGROUND: Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) as supportive features. Due to limited data regarding their relative and sequential value, there is no recommendation for an algorithm to combine both modalities to increase diagnostic accuracy. This study evaluated the added value of sequential imaging using state-of-the-art methods to analyse the images regarding PSP features. METHODS: The retrospective study included 41 PSP patients, 21 with Richardson's syndrome (PSP-RS), 20 with variant PSP phenotypes (vPSP) and 46 sex- and age-matched healthy controls. A pretrained support vector machine (SVM) for the classification of atrophy profiles from automatic MRI volumetry was used to analyse T1w-MRI (output: MRI-SVM-PSP score). Covariance pattern analysis was applied to compute the expression of a predefined PSP-related pattern in FDG-PET (output: PET-PSPRP expression score). RESULTS: The area under the receiver operating characteristic curve for the detection of PSP did not differ between MRI-SVM-PSP and PET-PSPRP expression score (p≥0.63): about 0.90, 0.95 and 0.85 for detection of all PSP, PSP-RS and vPSP. The MRI-SVM-PSP score achieved about 13% higher specificity and about 15% lower sensitivity than the PET-PSPRP expression score. Decision tree models selected the MRI-SVM-PSP score for the first branching and the PET-PSPRP expression score for a second split of the subgroup with normal MRI-SVM-PSP score, both in the whole sample and when restricted to PSP-RS or vPSP. CONCLUSIONS: FDG-PET provides added value for PSP-suspected patients with normal/inconclusive T1w-MRI, regardless of PSP phenotype and the methods to analyse the images for PSP-typical features.

Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy.

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Bifrontal electroconvulsive therapy leads to improvement of cerebral glucose hypometabolism in frontotemporal dementia with comorbid psychotic depression - a case report.

BACKGROUND: Differentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced. CASE PRESENTATION: Here, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient's delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT. CONCLUSIONS: In this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

PURPOSE: Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand 18F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression. METHODS: PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (VT) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance. RESULTS: In controls, VT was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean VT corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect. CONCLUSION: Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity.

Reliable quantification of 18F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio.

PURPOSE: Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand 18F-GE-180. This study tested simplified methods for quantification of 18F-GE-180 PET. METHODS: Dynamic 18F-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients. Population-based input function templates were generated by averaging individual input functions normalized to the total area under the input function using a leave-one-out approach. Individual population-based input functions were obtained by scaling the input function template with the individual parent activity concentration of 18F-GE-180 in arterial plasma in a blood sample drawn at 27.5 min or by the individual administered tracer activity, respectively. The total 18F-GE-180 distribution volume (VT) was estimated in 12 regions-of-interest (ROIs) by the invasive Logan plot using the measured or the population-based input functions. Late ROI-to-whole-blood and ROI-to-cerebellum ratio were also computed. RESULTS: Correlation with the reference VT (with individually measured input function) was very high for VT with the population-based input function scaled with the blood sample and for the ROI-to-whole-blood ratio (Pearson correlation coefficient = 0.989 ± 0.006 and 0.970 ± 0.005). The correlation was only moderate for VT with the population-based input function scaled with tracer activity dose and for the ROI-to-cerebellum ratio (0.653 ± 0.074 and 0.384 ± 0.177). Reference VT, population-based VT with scaling by the blood sample, and ROI-to-whole-blood ratio were sensitive to the TSPO gene polymorphism. Population-based VT with scaling to the administered tracer activity and the ROI-to-cerebellum ratio failed to detect a polymorphism effect. CONCLUSION: These results support the use of a population-based input function scaled with a single blood sample or the ROI-to-whole-blood ratio at a late time point for simplified quantitative analysis of 18F-GE-180 PET.

A randomized, double-blind, crossover comparison of novel continuous bed motion versus traditional bed position whole-body PET/CT imaging.

PURPOSE: Continuous bed motion has recently been introduced for whole-body PET/CT, and represents a paradigm shift towards individualized and flexible acquisition without the limitations of bed position-based planning. Increased patient comfort due to lack of abrupt table position changes may be another albeit still unproven advantage. For robust clinical implementation, image quality and quantitative accuracy should at least be equal to the prior standard of bed position-based step-and-shoot imaging. METHODS: The study included 68 consecutive patients referred for whole-body PET/CT for various malignancies. The patients underwent traditional step-and-shoot and novel continuous bed motion acquisition in the same session in a randomized crossover design. The patients and two independent observers were blinded to the sequence of scan techniques. Patient comfort/satisfaction was examined using a standardized questionnaire. SUVs were compared for reference tissue (liver, muscle) and tumour lesions. PET image quality and misalignment with CT images were evaluated on a scale of 1 - 4. RESULTS: Patients preferred continuous bed motion over step-and-shoot (P = 0.0001). It was considered to be more relaxing (38 % vs. 8 %), quieter (34 % vs. 8 %), and more fluid (64 % vs. 8 %). Image quality, SUV and CT misalignment did not differ between the techniques. Continuous bed motion resulted in better end-plane image quality (P < 0.0001). Regardless of the technique, second examinations had significantly higher tumour lesion SUVmax values (P = 0.0002), and a higher CT misalignment score (P = 0.0017). CONCLUSION: Oncological PET/CT with continuous bed motion enhances patient comfort and is associated with image quality at least comparable to that with traditional bed position-based step-and-shoot acquisition.qq.

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BACKGROUND: Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. METHODS: The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. RESULTS: Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. CONCLUSIONS: This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

Cirrhosis-related Parkinsonism: prevalence, mechanisms and response to treatments.

BACKGROUND & AIMS: Extrapyramidal and cerebellar symptoms belong to the most prominent features of episodic hepatic encephalopathy, and usually decrease upon ammonia-lowering therapy. Rapidly progressing parkinsonian symptoms, which are unresponsive to treatment of hepatic encephalopathy, indicate cirrhosis-related Parkinsonism. This study aims at analyzing the prevalence of cirrhosis-related Parkinsonism in patients with liver cirrhosis, and to study the functional status of the striatal dopaminergic system in these patients. METHODS: 214 patients with liver cirrhosis who were consecutively seen at the out-patient clinic for liver transplant candidates and/or at the transplantation wards at Hannover Medical School, between August 1, 2008 and March 31, 2011, underwent a standardized neurological examination while on the waiting list or immediately after liver transplantation. Single photon emission computer tomography (SPECT) using (123)I-beta-CIT, for the evaluation of the striatal dopamine transporter function, and (123)I-IBZM for the evaluation of the striatal dopamine D2 receptor availability, was performed in 6 patients with cirrhosis-related Parkinsonism. RESULTS: Cirrhosis-related Parkinsonism was diagnosed in 9 of 214 patients (4.2%). SPECT revealed significantly decreased dopamine receptor availability in 5 of 6 patients studied, and significantly decreased dopamine transporter availability in 3. Levodopa improved motor dysfunction in two of four patients treated, although only temporarily. Incomplete recovery was observed in two patients after liver transplantation. CONCLUSIONS: Cirrhosis-related Parkinsonism is more frequent than presumed. The presented data suggest pre- and postsynaptic alteration of striatal dopaminergic neurotransmission as a possible cause of cirrhosis-related Parkinsonism and reveal the limited effects of dopaminergic therapy.

Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: a clinical and positron emission tomography--computed tomography analysis.

PURPOSE: Treating segmental long-bone defects remains a major challenge. For defects >3 cm, segmental transport represents the gold standard, even though the method is time consuming and afflicted with several complications. The aim of this study was to evaluate healing of such defects after grafting an osteogenic scaffold previously seeded with stem cell concentrate. METHODS: We evaluated five patients with segmental long-bone defects (3-14 cm) treated with bone marrow aspirate concentrates (BMAC) seeded onto a bovine xenogenous scaffold. The healing process was monitored by X-rays and positron emission tomography-computed tomography (PET-CT) three months after surgery. RESULTS: Centrifugation led to a concentration of leukocytes by factor 8.1 ± 7.5. Full weight bearing was achieved 11.3 ± 5.0 weeks after surgery. PET analysis showed an increased influx of fluoride by factor 8.3 ± 6.4 compared with the contralateral side (p < 0.01). Bone density in the cortical area was 75 ± 16 % of the contralateral side (p < 0.03). The patient with the largest defect sustained an implant failure in the distal femur and finally accomplished therapy by segmental transport. He also had the lowest uptake of fluoride of the patient collective (2.2-fold increase). CONCLUSION: Stem cell concentrates can be an alternative to segmental bone transport. Further studies are needed to compare this method with autologous bone grafting and segmental transport.

Case report: Early-onset Parkinson's disease with initial spastic paraparesis and hyperreflexia caused by compound heterozygous PRKN-gene exon 2 and 4 deletions.

Pathogenic variants in the Parkin-gene (PRKN) are among the most common genetic causes of early onset Parkinson's disease (EOPD). Patients with EOPD can present with atypical clinical features and misdiagnosis is frequent. Here, we report a clinical phenotype with atypical signs and symptoms of a 35-year-old male patient with EOPD caused by a compound heterozygous PRKN-gene deletion of exons 2 and 4. After the initial diagnosis of stiff person syndrome, the patient was admitted to our department for a second opinion after 8 years of untreated disease progression. The patient presented with prominent spastic paraparesis pronounced on the right side and hyperreflexia as well as Parkinsonism with rigidity predominantly affecting the upper limbs, bradykinesia, and resting tremor. In the diagnostic assessment, magnetic evoked potentials to the anterior tibial muscles showed a low amplitude on the right side, compatible with pyramidal tract disturbance. However, an MRI of the head and the spine did not show any pathologies or atrophy. A [123I] FP-CIT SPECT scan revealed profoundly and left-pronounced reduced striatal uptake suggesting a neurodegenerative Parkinson's syndrome. Even though an acute levodopa challenge did not show marked improvement of symptoms, the chronic levodopa challenge with up to 450 mg/day significantly reduced the rigidity and bradykinesia. Surprisingly, spastic paraparesis and hyperreflexia diminished under dopaminergic treatment. Finally, genetic analysis by next-generation sequencing via copy number variant analysis (CNV) and multiplex ligation-dependent probe amplification (MLPA) confirmed compound heterozygous deletions of exons 2 and 4 in the PRKN-gene. As presented in this case, the awareness of atypical clinical symptoms of EOPD is essential to prevent misdiagnosis in young patients.

An unusual presentation of Huntington's disease.

We describe the case of a 59-year-old woman who exhibited psychotic symptoms, cognitive dysfunction, and restlessness. While the clinical picture and 18F-FDG PET/CT suggested the presence of a tauopathy, especially frontotemporal dementia or progressive supranuclear palsy, genetic testing eventually revealed Huntington's disease.

Estimation of glomerular filtration rate in liver-transplanted children: comparison of simplified procedures using 51Cr-EDTA and endogenous markers with Sapirstein's method as a reference standard.

This study evaluated simple procedures for GFR determination in 48 liver-transplanted children. After injection of (51)Cr-EDTA, blood samples were obtained up to four h, and activity retention in the body was measured for 60 min with scintillation probes. As a reference, GFR was calculated according to Sapirstein. Simplified calculations were performed according to Brochner-Mortensen, Russel, Devaux and Oberhausen. Additionally, GFR was determined using plasma creatinine and cystatin C according to Schwartz and Filler, respectively. The reference revealed mildly reduced GFR (62 +/- 20 mL/min/1.73 m(2)). Russel's method provided the highest degree of correlation (r(2) = 0.95), the smallest bias in GFR determination (-2%), and only one false exclusion plus one false diagnosis of chronic kidney disease. Oberhausen's method with blood sampling at one h post-injection performed slightly worse (r(2) = 0.67, bias: 3%). All other methods resulted in significantly different GFR estimates compared to the reference. Nevertheless, notably, the second narrowest 95% limits of agreement (-31% to 45%) was observed using cystatin C. In conclusion, this data implies to prefer Russel's method as a simplified procedure, and if patients cannot be available long enough (four h) for measurements, Oberhausen's method instead. If radiotracer methods are not available at all or for screening GFR, cystatin C appears to be the procedure of choice.

Combined Brain-Perfusion SPECT and EEG Measurements Suggest Distinct Strategies for Speech Comprehension in CI Users With Higher and Lower Performance.

Cochlear implantation constitutes a successful therapy of inner ear deafness, with the majority of patients showing good outcomes. There is, however, still some unexplained variability in outcomes with a number of cochlear-implant (CI) users, showing major limitations in speech comprehension. The current study used a multimodal diagnostic approach combining single-photon emission computed tomography (SPECT) and electroencephalography (EEG) to examine the mechanisms underlying speech processing in postlingually deafened CI users (N = 21). In one session, the participants performed a speech discrimination task, during which a 96-channel EEG was recorded and the perfusions marker 99mTc-HMPAO was injected intravenously. The SPECT scan was acquired 1.5 h after injection to measure the cortical activity during the speech task. The second session included a SPECT scan after injection without stimulation at rest. Analysis of EEG and SPECT data showed N400 and P600 event-related potentials (ERPs) particularly evoked by semantic violations in the sentences, and enhanced perfusion in a temporo-frontal network during task compared to rest, involving the auditory cortex bilaterally and Broca's area. Moreover, higher performance in testing for word recognition and verbal intelligence strongly correlated to the activation in this network during the speech task. However, comparing CI users with lower and higher speech intelligibility [median split with cutoff + 7.6 dB signal-to-noise ratio (SNR) in the Göttinger sentence test] revealed for CI users with higher performance additional activations of parietal and occipital regions and for those with lower performance stronger activation of superior frontal areas. Furthermore, SPECT activity was tightly coupled with EEG and cognitive abilities, as indicated by correlations between (1) cortical activation and the amplitudes in EEG, N400 (temporal and occipital areas)/P600 (parietal and occipital areas) and (2) between cortical activation in left-sided temporal and bilateral occipital/parietal areas and working memory capacity. These results suggest the recruitment of a temporo-frontal network in CI users during speech processing and a close connection between ERP effects and cortical activation in CI users. The observed differences in speech-evoked cortical activation patterns for CI users with higher and lower speech intelligibility suggest distinct processing strategies during speech rehabilitation with CI.

Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines.

There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.

Severe Progressive Multifocal Leukoencephalopathy (PML) and Spontaneous Immune Reconstitution Inflammatory Syndrome (IRIS) in an Immunocompetent Patient.

Background: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with JC-virus (JCV), a papova-virus, affecting mostly oligodendrocytes and the white matter of the central nervous system. Progressive Multifocal Leukoencephalopathy (PML) almost exclusively occurs in immunocompromised patients based on different underlying conditions of severe cellular immunodeficiency such as HIV/AIDS, secondary to neoplastic and autoimmune diseases, or during immunosuppressive therapy. Case presentation: We present the case of an otherwise healthy and immunocompetent patient without immunosuppressive therapy who was admitted with hemianopsia to the right side, sensory aphasia and changes of behavior. Magnet resonance imaging (MRI) and laboratory testing confirmed the diagnosis of PML, although functional tests did not show any evidence for cellular immunodeficiency. Extensive immunological tests did not reveal an apparent immunodeficiency. During symptomatic therapy the patient developed seizures which were assumed to be caused by a spontaneous immune reconstitution inflammatory syndrome (IRIS) demonstrated by MRI. We added a high dose of intravenous corticosteroids to the antiepileptic treatment and seizures ended shortly thereafter. However, the impairments of vision, behavior and language persisted. Conclusions: Our case report highlights that an apparently immunocompetent patient can develop PML and IRIS spontaneously. Therefore, MRI should be applied immediately whenever a rapid progression of PML symptoms occurs as treatment of IRIS with corticosteroids can result in a marked clinical improvement.

Computed tomography assessment of cerebral perfusion using a distributed parameter tracer kinetics model: validation with H(2)((15))O positron emission tomography measurements and initial clinical experience in patients with acute stroke.

We describe a distributed parameter (DP) model for tracer kinetic analysis in brain and validate the derived perfusion values with positron emission tomography (PET) scans. The proposed model is applied on actual clinical cases of hemispheric stroke. Nine patients with experienced transient ischaemic attack or minor stroke and a stenosis of the internal carotid artery were referred for computed tomography (CT) and PET imaging. The applicability of the DP model in clinical practice was tested in seven patients with acute stroke who received a baseline perfusion CT study and a noncontrast follow-up CT study after 2.4+/-1.8 days. The mean blood flow (F) value for all patients with carotid stenosis in the pooled data (54 regions of interest (ROIs)) was 37.9+/-11.2 mL/min per 100 g in perfusion CT and 35.6+/-9.8 mL/min per 100 g in perfusion PET imaging [r=0.77 (P=0.00)]. Regression analysis of the pooled ROIs for every patient revealed significant correlation between F values in seven patients [r=0.50 to 0.79 (r(2)-values ranged from 0.45 to 0.79), (0.01 < or = P < or = 0.05)]. Parametric maps that corresponded to all physiologic parameters were generated for every perfusion CT in the patients with acute stroke using the DP model. The ischaemic area was better delineated in F, intravascular blood volume and lag time (t(lag)) maps. The correlation coefficient comparing the visually outlined regions of abnormality between the t(lag) parametric map and the follow-up CT scans was 0.81 (P=0.003). In conclusion, DP physiological model using more realistic pharmacokinetics is feasible in dynamic contrast-enhanced CT of the brain in patients with acute and chronic cerebrovascular disease.

Correlates of local cerebral blood flow (CBF) in normal pressure hydrocephalus patients before and after shunting--A retrospective analysis of [(15)O]H(2)O PET-CBF studies in 65 patients.

OBJECTIVES: Findings in local cerebral blood flow (rCBF) in Normal pressure hydrocephalus (NPH) have always been challenged by the variable and inconsistent relation to clinical symptoms before and after shunt treatment. [(15)O]H(2)O PET data from a consecutive cohort of 65 idiopathic NPH patients were retrospectively analyzed questioning whether the functional status before and after shunt treatment might correlate with local blood flow. PATIENTS AND METHODS: Using statistical parametric mapping (SPM99, Wellcome Department of Cognitive Neurology, London), the [(15)O]H(2)O uptake was correlated with the preoperative clinical scores, graded according to a modified Stein and Langfitt score. Furthermore, differences in the uptake in the pre-and post-shunt treatment study after seven to 10 days in patients with and without clinical improvement were studied. RESULTS: A higher clinical score significantly correlated with a reduced tracer uptake in mesial frontal (k=1,239 voxel, Z=4.41) and anterior temporal (k=469, Z=4.07) areas. In the mesial frontal areas, tracer uptake showed significant reciprocal changes in the clinically improved vs. the unimproved patients. CONCLUSION: Matched with the existing literature, the regional blood flow alterations are suggested relevant to the NPH syndrome and to post-treatment functional changes. The present rCBF findings warrant prospective studies on the accuracy of neuroimaging studies as they may provide a more specific insight into disease mechanisms.

Activation in the auditory pathway of the gerbil studied with 18F-FDG PET: effects of anesthesia.

Here, we present results from an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) study in the Mongolian gerbil, a preferred animal model in auditory research. One major issue in preclinical nuclear imaging, as well as in most of the neurophysiological methods investigating auditory processing, is the need of anesthesia. We compared the usability of two types of anesthesia which are frequently employed in electrophysiology, ketamine/xylazine (KX), and fentanyl/midazolam/medetomidine (FMM), for valid measurements of auditory activation with 18F-FDG PET. Gerbils were placed in a sound-shielding box and injected with 18F-FDG. Two acoustic free-field conditions were used: (1) baseline (no stimulation, 25 dB background noise) and (2) 90 dB frequency-modulated tones (FM). After 40 min of 18F-FDG uptake, a 30 min acquisition was performed using a small animal PET/CT system. Blood glucose levels were measured after the uptake phase before scanning. Standardized uptake value ratios for relevant regions were determined after implementing image and volume of interest templates. Scans demonstrated a significantly higher uptake in the inferior colliculus with FM stimulation compared to baseline in awake subjects (+ 12%; p = 0.02) and with FMM anesthesia (+ 13%; p = 0.0012), but not with KX anesthesia. In non-auditory brain regions, no significant difference was detected. Blood glucose levels were significantly higher under KX compared to FMM anesthesia (17.29 ± 0.42 mmol/l vs. 14.30 ± 1.91 mmol/l; p = 0.024). These results suggest that valid 18F-FDG PET measurements of auditory activation comparable to electrophysiology can be obtained from gerbils during opioid-based anesthesia due to its limited effects on interfering blood glucose levels.