Cerebral Glucose Metabolism Is a Valuable Predictor of Survival in Patients with Lewy Body Diseases.

OBJECTIVE: Patients with Lewy body diseases have an increased risk of dementia, which is a significant predictor for survival. Posterior cortical hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (PET) precedes the development of dementia by years. We therefore examined the prognostic value of cerebral glucose metabolism for survival. METHODS: We enrolled patients diagnosed with Parkinson's disease (PD), Parkinson's disease with dementia, or dementia with Lewy bodies who underwent [18F]fluorodeoxyglucose PET. Regional cerebral metabolism of each patient was analyzed by determining the expression of the PD-related cognitive pattern (Z-score) and by visual PET rating. We analyzed the predictive value of PET for overall survival using Cox regression analyses (age- and sex-corrected) and calculated prognostic indices for the best model. RESULTS: Glucose metabolism was a significant predictor of survival in 259 included patients (n = 118 events; hazard ratio: 1.4 [1.2-1.6] per Z-score; hazard ratio: 1.8 [1.5-2.2] per visual PET rating score; both p < 0.0001). Risk stratification with visual PET rating scores yielded a median survival of 4.8, 6.8, and 12.9 years for patients with severe, moderate, and mild posterior cortical hypometabolism (median survival not reached for normal cortical metabolism). Stratification into 5 groups based on the prognostic index revealed 10-year survival rates of 94.1%, 78.3%, 34.7%, 0.0%, and 0.0%. INTERPRETATION: Regional cerebral glucose metabolism is a significant predictor of survival in Lewy body diseases and may allow an earlier survival prediction than the clinical milestone "dementia." Thus, [18F]fluorodeoxyglucose PET may improve the basis for therapy decisions, especially for invasive therapeutic procedures like deep brain stimulation in Parkinson's disease. ANN NEUROL 2024;96:539-550.

Performance of cone-beam computed tomography (CBCT) in comparison to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone invasion in oral squamous cell cancer (OSCC): a prospective study.

BACKGROUND: Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC. METHODS: We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities. RESULTS: Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI. CONCLUSION: Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.

Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy.

Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [123I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical work-up including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [123I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [123I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 ± 0.63 vs. 2.91 ± 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 ± 0.51 vs. 2.74 ± 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.

Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [18F]FDG PET/CT and MRI.

PURPOSE: While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. METHODS: Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. RESULTS: [18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. CONCLUSION: FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.

Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.

Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics.

Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson's disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4-13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson's disease and suggests that freezing of gait is a 'circuitopathy' related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson's disease should aim at directly targeting derangements of neural network dynamics.

Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy.

PURPOSE: Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance of 18F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed. METHODS: Twenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwent 18F-florbetaben-PET/CT for diagnostic work-up. Qualitative and quantitative assessment including calculation of myocardial tracer retention (MTR) was performed, and compared to echo (n = 20), CMR (n = 16), scintigraphy (n = 16) and serologic biomarkers (NT-proBNP, cTnT, free light chains). In four patients, follow-up PET/CT was available (after treatment initiation, n = 3; surveillance, n = 1). RESULTS: PET demonstrated myocardial 18F-florbetaben retention consistent with CA in 14/22 patients. Suspicion of CA was subsequently dropped in all eight PET-negative patients. Amyloid subtypes showed characteristic retention patterns (AL > AA > ATTR; all p < 0.005). MTR correlated with morphologic and functional parameters, as measured by CMR and echo (all r| > 0.47|, all p < 0.05), but not with cardiac biomarkers. Changes in MTR from baseline to follow-up corresponded well to treatment response, as assessed by cardiac biomarkers and performance status. CONCLUSIONS: Imaging of cardiac amyloidosis (CA) with 18F-florbetaben-PET/CT is feasible and might be useful in differentiating CA subtypes.

Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease.

Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = -0.377, p = 0.048), with olfactory function (ρ = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs.

Deformation-based morphometry applied to FDG PET data reveals hippocampal atrophy in Alzheimer's disease.

Cerebral atrophy is a key finding in patients with dementia and usually determined on MRI. We tested whether cerebral atrophy can be imaged with FDG PET by applying deformation-based morphometry (DBM). We retrospectively identified 26 patients with a biomarker-supported clinical diagnosis of Alzheimer's disease (AD) who had received FDG PET on a fully-digital PET/CT system and structural MRI and compared them to 13 healthy elderly controls (HEC). We performed DBM with FDG PET data (FDG-DBM). As a reference standard for determining atrophy we used voxel-based morphometry of MRI data (MRI-VBM). For conventional analysis of hypometabolism, scaled FDG PET scans (reference: brain parenchyma) were compared between groups. Receiver operating characteristic (ROC) analyses were performed. ROI read-outs were tested for associations with cognitive test performance. FDG-DBM showed abnormalities in AD mainly in the bilateral hippocampi. Similarly, MRI-VBM showed hippocampal atrophy. By contrast, conventional FDG PET analysis revealed reduced bilateral temporo-parietal FDG uptake (all p < 0.05, FWE-corrected). FDG-DBM measures of the hippocampus significantly separated AD from HEC with an AUC of 0.81; MRI-VBM achieved an AUC of 0.87; the difference between the two ROC curves was not significant (p = 0.40). Whereas FDG uptake of the hippocampus did not separate AD from HEC, FDG uptake of the Landau Meta-ROI achieved an AUC of 0.88. Verbal memory was significantly associated with FDG-DBM measures of the hippocampus (p = 0.009), but not of the Landau Meta-ROI (p > 0.1). The opposite held true for conventional FDG uptake (p > 0.1 and p = 0.001, respectively). Hippocampal atrophy in AD can be detected by applying DBM to clinical, fully-digital FDG PET. It correlates with cognitive performance and might constitute a biomarker of neurodegeneration that is complementary to conventional FDG PET analysis of regional hypometabolism.

Targeting TGFß-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome.

Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. Here we examined the role of microglia using mouse models and cohorts of individuals with ICANS. CD19-directed CAR (CAR19) T cell transfer in B cell lymphoma-bearing mice caused microglia activation and neurocognitive deficits. The TGFß-activated kinase-1 (TAK1)-NF-κB-p38 MAPK pathway was activated in microglia after CAR19 T cell transfer. Pharmacological TAK1 inhibition or genetic Tak1 deletion in microglia using Cx3cr1CreER:Tak1fl/fl mice resulted in reduced microglia activation and improved neurocognitive activity. TAK1 inhibition allowed for potent CAR19-induced antilymphoma effects. Individuals with ICANS exhibited microglia activation in vivo when studied by translocator protein positron emission tomography, and imaging mass cytometry revealed a shift from resting to activated microglia. In summary, we prove a role for microglia in ICANS pathophysiology, identify the TAK1-NF-κB-p38 MAPK axis as a pathogenic signaling pathway and provide a rationale to test TAK1 inhibition in a clinical trial for ICANS prevention after CAR19 T cell-based cancer immunotherapy.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting as cortisone sensible psychosis with reversible leukoencephalopathy.

INTRODUCTION: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a frequently discussed neuropsychiatric syndrome with elevated thyroid antibodies in the context of various clinical neuropsychiatric phenotypes. MRI abnormalities are usually nonspecific and treatment can be complex. CASE STUDY: We present a case of a woman in her sixties with SREAT whose psychosis kept worsening under cortisone tapering. After three years with cortisone side effects, therapy was changed to plasmapheresis and rituximab treatment with an excellent initial response, subacute unexplained deterioration with extensive leukoencephalopathy on MRI shortly after, and full recovery with regression of leukoencephalopathy afterwards. DISCUSSION: SREAT varies in clinical and diagnostic presentation. Its precise pathophysiology is unknown, as are the best treatment protocols. The case illustrates that some patients with SREAT syndrome might end up in constellations, in which it proves difficult to wean off steroid treatment and illustrates treatment alternatives such as plasmapheresis and/or rituximab. In addition, it highlights leukoencephalopathy as possible MRI finding in the context of SREAT. Further research is necessary to fully comprehend the (potentially different) pathomechanisms and courses of SREAT.

Quantification of the purinergic P2X7 receptor with [11C]SMW139 improves through correction for brain-penetrating radiometabolites.

The membrane-based purinergic 7 receptor (P2X7R) is expressed on activated microglia and the target of the radioligand [11C]SMW139 for in vivo assessment of neuroinflammation. This study investigated the contribution of radiolabelled metabolites which potentially affect its quantification. Ex vivo high-performance liquid chromatography with a radio detector (radioHPLC) was used to evaluate the parent and radiometabolite fractions of [11C]SMW139 in the brain and plasma of eleven mice. Twelve healthy humans underwent 90-min [11C]SMW139 brain PET with arterial blood sampling and radiometabolite analysis. The volume of distribution was estimated by using one- and two- tissue compartment (TCM) modeling with single (VT) and dual (VTp) input functions. RadioHPLC showed three major groups of radiometabolite peaks with increasing concentrations in the plasma of all mice and humans. Two radiometabolite peaks were also visible in mice brain homogenates and therefore considered for dual input modeling in humans. 2TCM with single input function provided VT estimates with a wide range (0.10-10.74) and high coefficient of variation (COV: 159.9%), whereas dual input function model showed a narrow range of VTp estimates (0.04-0.24; COV: 33.3%). In conclusion, compartment modeling with correction for brain-penetrant radiometabolites improves the in vivo quantification of [11C]SMW139 binding to P2X7R in the human brain.

[Transference interpretations and how they work: a systematic review]. / Was sind übertragungsdeutungen und wie wirken sie? Eine systematische übersicht.

In clinical theory transference interpretations represent a central therapeutic technique and a specific mechanism of change in psychodynamic psychotherapies. However, the empirical basis lags behind the theoretical considerations. This article reviews both the results of empirical research on transference interpretations and their definitions of the measures employed (systematic database search for the timespan 1970-2011). The empirical results are rather heterogeneous and in part contradictory. As it turns out, specific patient characteristics (e.g., the quality of object relations), the amount and quality of transference interpretations as well as the patients' immediate reaction all decisively influence the potency of the change of transference interpretations. Currently, it is not possible to develop clear therapeutic strategies based on previous findings. Careful use of transference interpretations is generally recommended. Various methods for measuring transference interpretations exist, but the definitions do not correspond completely. A standardization of definitions would increase the comparability and interpretability of findings and greatly improve concordance with theory.

Nigral glucose metabolism as a diagnostic marker of neurodegenerative parkinsonian syndromes.

Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are characterized by nigrostriatal degeneration. We used [18F]FDG PET to assess glucose metabolism of the substantia nigra (SN) in patients with these diseases and evaluated its ability to discriminate neurodegenerative parkinsonian syndromes (NP) from controls. We retrospectively evaluated [18F]FDG PET scans of 171 patients with NP (n = 115 PD, n = 35 MSA, n = 21 PSP) and 48 controls (13 healthy controls [HC] and 35 control patients). Mean normalized bilateral [18F]FDG uptake in the SN was calculated and compared between groups with covariance and receiver operating characteristic (ROC) analyses (selection of the optimal cut-off required a minimum specificity of 90% to meet the clinical need of a confirmatory test). PD patients were additionally stratified by the expression of the well-established PD-related metabolic pattern (PDRP; elevated expression defined as 2 standard deviations above the mean value of HC). [18F]FDG uptake was significantly lower in NP (Cohen's d = 1.09, p < 0.001) and its subgroups (PD, d = 1.10, p < 0.001; MSA, d = 0.97, p < 0.001; PSP, d = 1.79, p < 0.001) than in controls. ROC analysis for discriminating NP vs. controls revealed an area under the curve of 0.81 and a sensitivity and specificity of 56 and 92%. Moreover, nigral metabolism was below the cut-off in 60% of PD patients without elevated PDRP expression. Glucose metabolism of the SN can distinguish patients with NP from controls with good diagnostic accuracy and can be used as a marker of nigral degeneration. Its evaluation is particularly valuable in PD patients without elevated PDRP expression and may thus help to narrow the diagnostic gap of [18F]FDG PET in neurodegenerative parkinsonism (i.e., identification of patients with PD without cortical involvement).

Reduced Segmentation of Lesions Is Comparable to Whole-Body Segmentation for Response Assessment by PSMA PET/CT: Initial Experience with the Keyhole Approach.

(1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUVmax were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUVmaxall, ΔSUVmax10, ΔSUVmax5, ΔPSMA-TVall, ΔPSMA-TV10, ΔPSMA-TV5, ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUVmax10/ΔSUVmax5 or ΔPSMA-TV10/ΔPSMA-TV5 compared to ΔSUVmaxall and ΔPSMA-TVall. For patients treated with taxanes, up to 6/21 (28.6%) showed clinically relevant deviations between ΔSUVmaxall and ΔSUVmax10 or ΔSUVmax5, but only up to 2/21 (9.5%) patients showed clinically relevant deviations between ΔPSMA-TVall and ΔPSMA-TV10 or ΔPSMA-TV5. For patients treated with radioligand therapy (RLT), up to 5/28 (17.9%) showed clinically relevant deviations between ΔSUVmaxall and ΔSUVmax10 or ΔSUVmax5, but only 1/28 (3.6%) patients showed clinically relevant deviations between ΔPSMA-TVall and ΔPSMA-TV10 or ΔPSMA-TV5. The highest correlations with ΔPSA were found for ΔPSMA-TVall (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV10 (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV5 (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUVmaxall (r = 0.60, p = 0.02) and with ΔSUVmax10 (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUVmaxall (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.

[18F]FDG-PET/CT improves the detection of synchronous malignancies at primary staging of oral squamous cell carcinoma - A retrospective study.

The purpose of this study was to show the non-inferiority of [18F]FDG-PET/CT compared with panendoscopy with regards to secondary malignancies of the UADT, and to evaluate the diagnostic performance of PET/CT for detecting synchronous malignancies. Patients with newly diagnosed OSCC and both panendoscopy and [18F]FDG-PET/CT at primary staging were enrolled in this retrospective study. The accuracy in detecting synchronous malignancies was assessed for both modalities, and their diagnostic measures for the detection of malignancies within the UADT were compared. Histopathological analysis and clinical follow-up served as reference standards. In total, 182 patients were enrolled in this study. Eighteen patients (9.9%) had in total 22 synchronous malignancies, of which eight were located within the UADT. [18F]FDG-PET/CT detected all malignancies within the whole body (sensitivity: 100%) and yielded false-positive results in four cases (specificity: 97.6%). Sensitivity ([18F]FDG-PET/CT: 100% vs panendoscopy: 87.5%), specificity (99.4% vs 100%), negative predictive value (100% vs 99.4%), and positive predictive value (88.9% vs 100%) for detecting secondary UADT malignancies did not differ between modalities (all p = 0.32). Within the limitations of the study it seems that [18F]FDG-PET/CT detects synchronous malignancies of the UADT with an accuracy comparable to panendoscopy, and enables highly sensitive whole-body tumor screening in patients with newly diagnosed OSCC. This could be a relevant factor for therapeutic decision making in clinical routine.

Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? - Additional clinical and neuroimaging evidence.

BACKGROUND: Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. OBJECTIVE: Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. METHODS: We retrospectively studied operationalized and quantitative analyses of tremor and gait, as well as [18F]fluorodeoxyglucose (FDG) PET of 12 patients affected by therapy escape. All examinations were carried out with activated DBS (ON) and 72 h after deactivation (OFF72h); gait and tremor were also analyzed directly after deactivation (OFF0h). Changes of normalized glucose metabolism between stimulation conditions were assessed using within-subject analysis of variance and statistical parametric mapping. Additionally, a comparison to the [18F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. RESULTS: Of the immediately accessible parametric tremor data (i.e. ON or OFF0h) only the rebound (i.e. OFF0h) frequency of postural tremor showed possible correlations with signs of ataxia at ON. Regional glucose metabolism was significantly increased bilaterally in the thalamus and dentate nucleus in ON compared to OFF72h. No differences in regional glucose metabolism were found in patients in ON and OFF72h compared with the healthy controls. CONCLUSIONS: Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.