Persistent brain metabolic impairment in long COVID patients with persistent clinical symptoms: a nine-month follow-up [18F]FDG-PET study.

PURPOSE: A hypometabolic profile involving the limbic areas, brainstem and cerebellum has been identified in long COVID patients using [18F]fluorodeoxyglucose (FDG)-PET. This study was conducted to evaluate possible recovery of brain metabolism during the follow-up of patients with prolonged symptoms. METHODS: Fifty-six adults with long COVID who underwent two brain [18F]FDG-PET scans in our department between May 2020 and October 2022 were retrospectively analysed, and compared to 51 healthy subjects. On average, PET1 was performed 7 months (range 3-17) after acute COVID-19 infection, and PET2 was performed 16 months (range 8-32) after acute infection, because of persistent severe or disabling symptoms, without significant clinical recovery. Whole-brain voxel-based analysis compared PET1 and PET2 from long COVID patients to scans from healthy subjects (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected) and PET1 to PET2 (with the same threshold, and secondarily with a less constrained threshold of p-voxel < 0.005 uncorrected, p-cluster < 0.05 uncorrected). Additionally, a region-of-interest (ROI) semiquantitative anatomical approach was performed for the same comparisons (p < 0.05, corrected). RESULTS: PET1 and PET2 revealed voxel-based hypometabolisms consistent with the previously reported profile in the literature. This between-group analysis comparing PET1 and PET2 showed minor improvements in the pons and cerebellum (8.4 and 5.2%, respectively, only significant under the less constrained uncorrected p-threshold); for the pons, this improvement was correlated with the PET1-PET2 interval (r = 0.21, p < 0.05). Of the 14,068 hypometabolic voxels identified on PET1, 6,503 were also hypometabolic on PET2 (46%). Of the 7,732 hypometabolic voxels identified on PET2, 6,094 were also hypometabolic on PET1 (78%). The anatomical ROI analysis confirmed the brain hypometabolism involving limbic region, the pons and cerebellum at PET1 and PET2, without significant changes between PET1 and PET2. CONCLUSION: Subjects with persistent symptoms of long COVID exhibit durable deficits in brain metabolism, without progressive worsening.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0.

PURPOSE: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands. METHODS: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). RESULTS: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma. CONCLUSION: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Peptide radionuclide radiation therapy with Lutathera in multirecurrent nonanaplastic meningiomas: antitumoral activity study by growth rate analysis.

PURPOSE: Several retrospective studies and meta-analyses of Peptide Radionuclide Radiation Therapy in meningiomas suggest six-month progression-free survival improvement for WHO grade 1 and 2 meningiomas. In the present study, we aimed to evaluate the impact of such treatment on three-dimensional volume growth rate (3DVGR) in nonanaplastic meningiomas. METHODS: The authors performed a retrospective study including eight patients treated with Lutathera®. Millimetric 3D T1-weighted with gadolinium enhancement magnetic resonance imaging sequences were requested for volume measurement. Then, tumor growth rate was classified following a previously described 3DVGR classification (Graillon et al.). RESULTS: Patients harbored seven WHO grade 2 meningiomas and one aggressive WHO grade 1. All patients, except one, underwent four treatment cycles. 3DVGR significantly decreased at 3, 6, and 12 months after treatment initiation analyzing each lesion separately. Mean and median 3DVGR from all patients were respectively at 29.5% and 44.5%/6 months before treatment initiation, then at 16.5% and 25%/6 months at three months post-treatment initiation, 9.5% and 4.5%/6 months after 6 months, as well as 9.5% and 10.5%/6 months after 12 months. At 3, 6, and 12 months after treatment initiation, 4/8, 6/7, and 5/6 patients were class 2 (stabilization or severe 3DVGR slowdown), respectively. No patient was class 1 at 6 and 12 months, suggesting a lack of drug response. CONCLUSION: In nonanaplastic meningiomas, Lutathera®'s antitumoral activity appeared delayed and more likely observed at six months, while no major response was observed under treatment. Moreover, its antitumoral activity persisted for 12-18 months following treatment initiation.

Metabolic patterns in brain 18F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia.

There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible deep brain stimulation surgery between September 2007 and February 2018 at Evelina London Children's Hospital (ELCH), UK, were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the 10 commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of 39 adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired cerebral palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1 and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. 'Signature' patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalized management strategies.

Regional brain glucose metabolism is differentially affected by ketogenic diet: a human semiquantitative positron emission tomography.

PURPOSE: Ketogenic diet (KD) is recommended to avoid intense [18F]FDG myocardial physiologic uptake in PET imaging. Neuroprotective and anti-seizure effects of KD have been suggested, but their mechanisms remain to be elucidated. This [18F]FDG PET study aims to evaluate the effect of KD on glucose brain metabolism. METHOD: Subjects who underwent KD prior to whole-body and brain [18F]FDG PET between January 2019 and December 2020 in our department for suspected endocarditis were retrospectively included. Myocardial glucose suppression (MGS) on whole-body PET was analyzed. Patients with brain abnormalities were excluded. Thirty-four subjects with MGS (mean age: 61.8 ± 17.2 years) were included in the KD population, and 14 subjects without MGS were considered for a partial KD group (mean age: 62.3 ± 15.1 years). Brain SUVmax was first compared between these two KD groups to determine possible global uptake difference. Semiquantitative voxel-based intergroup analyses were secondarily performed to determine possible inter-regional differences by comparing KD groups with and without MGS, separately, to 27 healthy subjects fasting for at least 6 h (mean age of 62.4 ± 10.9 years), and KD groups between them (p-voxel < 0.001, and p-cluster < 0.05, FWE-corrected). RESULTS: A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Student's t-test, p = 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them. CONCLUSION: KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.

The impact of COVID-19 lockdown on brain metabolism.

This study aims to evaluate the impact of French national lockdown of 55 days on brain metabolism of patients with neurological disorders. Whole-brain voxel-based PET analysis was used to correlate 18 F-FDG metabolism to the number of days after March 17, 2020 (in 95 patients; mean age: 54.3 years ± 15.7; 59 men), in comparison to the same period in 2019 before the SARS-CoV-2 outbreak (in 212 patients; mean age: 59.5 years ± 15.8; 114 men), and to the first 55 days of deconfinement (in 188 patients; mean age: 57.5 years ± 16.5; 93 men). Lockdown duration was negatively correlated to the metabolism of the sensory-motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap was found with the reported pattern of hypometabolism in long COVID (<9%). Restriction of physical activities, and possible related deconditioning, and social isolation may lead to functional disturbances of sensorimotor and emotional brain networks. Of note, this metabolic pattern seems distinct to those reported in long COVID. Further longitudinal studies with longer follow-up are needed to evaluate clinical consequences and relationships on cognitive and mental health against functional deactivation hypothesis, and to extend these findings to healthy subjects in the context of lockdown.

Single Photon Emission Computed Tomography/Positron Emission Tomography Molecular Imaging for Parkinsonism: A Fast-Developing Field.

The early differential diagnosis of Parkinson disease and atypical parkinsonism is a major challenge. The use of single photon emission computed tomography (SPECT)/positron emission tomography (PET) molecular imaging to investigate parkinsonism is a fast-developing field. Imaging biomarker research may potentially lead to more accurate disease detection, enabling earlier diagnosis and treatment. This review summarizes recent SPECT/PET advances in radiopharmaceuticals and imaging technologies/analyses that improve the diagnosis of neurodegenerative parkinsonism. We are currently witnessing a turning point in the field. Integrating molecular imaging as a diagnostic technique represents an opportunity to reassess the strategies for diagnosing neurodegenerative parkinsonism. ANN NEUROL 2021;90:711-719.

Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience.

BACKGROUND: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of 18F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum. METHODS: From the beginning of August 2021 to the end of October 2021, the brain 18F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain 18F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern. RESULTS: On the 143 brain 18F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles. CONCLUSION: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.

Similar patterns of [18F]-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series.

PURPOSE: Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical presentation has been referred as "long COVID" in the adult population, and an [18F]-FDG brain PET hypometabolic pattern has recently been suggested as a biomarker. Herein, we present a retrospective analysis of 7 paediatric patients with suspected long COVID who were explored by [18F]-FDG brain PET exam. Metabolic brain findings were confronted to those obtained in adult patients with long COVID, in comparison to their respective age-matched control groups. METHODS: Review of clinical examination and whole-brain voxel-based analysis of [18F]-FDG PET metabolism of the 7 children in comparison to 21 paediatric controls, 35 adult patients with long COVID and 44 healthy adult subjects. RESULTS: Despite lower initial severity at the acute stage of the infection, paediatric patients demonstrated on average 5 months later a similar brain hypometabolic pattern as that found in adult long COVID patients, involving bilateral medial temporal lobes, brainstem and cerebellum (p-voxel < 0.001, p-cluster < 0.05 FWE-corrected), and also the right olfactory gyrus after small volume correction (p-voxel = 0.010 FWE-corrected), with partial PET recovery in two children at follow-up. CONCLUSION: These results provide arguments in favour of possible long COVID in children, with a similar functional brain involvement to those found in adults, regardless of age and initial severity.

Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia.

PURPOSE: Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with persistent symptoms. METHODS: Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3 mg/L). The identified clusters were secondarily correlated with clinical symptoms. RESULTS: After adjustment for age, sex, educational level, illness duration, antidepressant use, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe, and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP levels < 3 mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative, and excitement symptoms under antipsychotic treatment. CONCLUSION: In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.

Decrease in the cortex/striatum metabolic ratio on [18F]-FDG PET: a biomarker of autoimmune encephalitis.

PURPOSE: The aim of this [18F]-FDG PET study was to determine the diagnostic value of the cortex/striatum metabolic ratio in a large cohort of patients suffering from autoimmune encephalitis (AE) and to search for correlations with the course of the disease. METHODS: We retrospectively collected clinical and paraclinical data of patients with AE, including brain 18F-FDG PET/CT. Whole-brain statistical analysis was performed using SPM8 software after activity parametrization to the striatum in comparison to healthy subjects. The discriminative performance of this metabolic ratio was evaluated in patients with AE using receiver operating characteristic curves against 44 healthy subjects and a control group of 688 patients with MCI. Relationship between cortex/striatum metabolic ratios and clinical/paraclinical data was assessed using univariate and multivariate analysis in patients with AE. RESULTS: Fifty-six patients with AE were included. In comparison to healthy subjects, voxel-based statistical analysis identified one large cluster (p-cluster < 0.05, FWE corrected) of widespread decreased cortex/striatum ratio in patients with AE. The mean metabolic ratio was significantly lower for AE patients (1.16 ± 0.13) than that for healthy subjects (1.39 ± 0.08; p < 0.001) and than that for MCI patients (1.32 ± 0.11; p < 0.001). A ratio threshold of 1.23 allowed to detect AE patients with a sensitivity of 71% and a specificity of 82% against MCI patients, and 98% against healthy subjects. A lower cortex/striatum metabolic ratio had a trend towards shorter delay before 18F-FDG PET/CT (p = 0.07) in multivariate analysis. CONCLUSION: The decrease in the cortex/striatal metabolic ratio has a good early diagnostic performance for the differentiation of AE patients from controls.

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3.

The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.

Correlation between fluorodeoxyglucose positron emission tomography brain hypometabolism and posttraumatic stress disorder symptoms in temporal lobe epilepsy.

The relationship between posttraumatic stress disorder (PTSD) and focal epilepsy is poorly understood. It has been hypothesized that there is a complex and reciprocal potential reinforcement of the symptoms of each condition. In this study, we investigated whether there are PTSD-specific brain changes in temporal lobe epilepsy (TLE). Brain fluorodeoxyglucose positron emission tomography (PET) metabolism was compared between controls and two groups of TLE patients: one group of 15 patients fulfilling the criteria for a potential diagnosis of PTSD (TLE-PTSD+), another group of 24 patients without a diagnosis of PTSD (TLE-PTSD-), and a group of 30 healthy control participants. We compared the differences in brain PET metabolism among these three groups, and we studied their correlations with interictal and peri-ictal scales of PTSD symptoms. TLE-PTSD+ patients showed more significant hypometabolism involving right temporal and right orbitofrontal cortex in comparison to TLE-PTSD- patients and healthy subjects. Moreover, degree of reduced metabolism in these brain areas correlated with interictal and peri-ictal PTSD questionnaire scores. PTSD in temporal epilepsy is associated with specific changes in neural networks, affecting limbic and paralimbic structures. This illustrates the close intertwining of epileptogenic and psychogenic processes in these patients.

FDG-PET to T1 Weighted MRI Translation with 3D Elicit Generative Adversarial Network (E-GAN).

OBJECTIVE: With the strengths of deep learning, computer-aided diagnosis (CAD) is a hot topic for researchers in medical image analysis. One of the main requirements for training a deep learning model is providing enough data for the network. However, in medical images, due to the difficulties of data collection and data privacy, finding an appropriate dataset (balanced, enough samples, etc.) is quite a challenge. Although image synthesis could be beneficial to overcome this issue, synthesizing 3D images is a hard task. The main objective of this paper is to generate 3D T1 weighted MRI corresponding to FDG-PET. In this study, we propose a separable convolution-based Elicit generative adversarial network (E-GAN). The proposed architecture can reconstruct 3D T1 weighted MRI from 2D high-level features and geometrical information retrieved from a Sobel filter. Experimental results on the ADNI datasets for healthy subjects show that the proposed model improves the quality of images compared with the state of the art. In addition, the evaluation of E-GAN and the state of art methods gives a better result on the structural information (13.73% improvement for PSNR and 22.95% for SSIM compared to Pix2Pix GAN) and textural information (6.9% improvements for homogeneity error in Haralick features compared to Pix2Pix GAN).

Early atypical signs and insula hypometabolism predict survival in multiple system atrophy.

OBJECTIVE: We aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA). METHODS: We included patients with a 'probable' MSA diagnosis for whom a clinical evaluation and a brain PET were performed early in the course of the disease (median 3 years, IQR 2-5). A retrospective analysis was conducted using standardised data collection. Brain PET metabolism was characterised using the Automated Anatomical Labelling Atlas. A Cox model was applied to look for factors influencing survival. Kaplan-Meier method estimated the survival rate. We proposed to develop a predictive 'risk score', categorised into low-risk and high-risk groups, using significant variables entered in multivariate Cox regression analysis. RESULTS: Eighty-five patients were included. The overall median survival was 8 years (CI 6.64 to 9.36). Poor prognostic factors were orthostatic hypotension (HR=6.04 (CI 1.58 to 23.12), p=0.009), stridor (HR=3.41 (CI 1.31 to 8.87), p=0.012) and glucose PET hypometabolism in the left insula (HR=0.78 (CI 0.66 to 0.92), p=0.004). Good prognostic factors were time to diagnosis (HR=0.68 (CI 0.54 to 0.86), p=0.001) and use of selective serotonin reuptake inhibitor (SSRI) (HR=0.17 (CI 0.06 to 0.46), p<0.001). The risk score revealed a 5-year gap separating the median survival of the two groups obtained (5 years vs 10 years; HR=5.82 (CI 2.94 to 11.49), p<0.001). CONCLUSION: The clinical prognosis factors we have described support published studies. Here, we also suggest that brain PET is of interest for prognosis assessment and in particular in the search for left insula hypometabolism. Moreover, SSRIs are a potential drug candidate to slow the progression of the disease.

Brain 18F-FDG PET for the diagnosis of autoimmune encephalitis: a systematic review and a meta-analysis.

OBJECTIVE: To consolidate current understanding of detection sensitivity of brain 18F-FDG PET scans in the diagnosis of autoimmune encephalitis and to define specific metabolic imaging patterns for the most frequently occurring autoantibodies. METHODS: A systematic and exhaustive search of data available in the literature was performed by querying the PubMed/MEDLINE and Cochrane databases for the search terms: ((PET) OR (positron emission tomography)) AND ((FDG) OR (fluorodeoxyglucose)) AND ((encephalitis) OR (brain inflammation)). Studies had to satisfy the following criteria: (i) include at least ten pediatric or adult patients suspected or diagnosed with autoimmune encephalitis according to the current recommendations, (ii) specifically present 18F-FDG PET and/or morphologic imaging findings. The diagnostic 18F-FDG PET detection sensitivity in autoimmune encephalitis was determined for all cases reported in this systematic review, according to a meta-analysis following the PRISMA method, and selected publication quality was assessed with the QUADAS-2 tool. RESULTS: The search strategy identified 626 articles including references from publications. The detection sensitivity of 18F-FDG PET was 87% (80-92%) based on 21 publications and 444 patients included in the meta-analysis. We also report specific brain 18F-FDG PET imaging patterns for the main encephalitis autoantibody subtypes. CONCLUSION AND RELEVANCE: Brain 18F-FDG PET has a high detection sensitivity and should be included in future diagnostic autoimmune encephalitis recommendations. Specific metabolic 18F-FDG PET patterns corresponding to the main autoimmune encephalitis autoantibody subtypes further enhance the value of this diagnostic.

Insular interictal positron emission tomography hypometabolism in patients with ictal asystole.

We aimed to explore brain area(s) involved in the generation of ictal asystole (IA) by analyzing the interictal positron emission tomography (PET) metabolism of patients with IA recorded by video-electroencephalography or video-stereo-electroencephalography. We identified in our cohort of focal epilepsy patients who had undergone presurgical evaluation those who had a recorded period of IA of more than 3 s. We investigated the anatomometabolic changes (interictal 18 F-fluorodeoxyglucose PET) of these patients in comparison with (1) healthy subjects with similar age and sex distribution (n = 19) using whole-brain voxel-based analysis (p-voxel < .001, p-cluster < .05, uncorrected) and (2) patients without IA with similar age and seizure onset zone (n = 55). We found 12 patients with IA. Epilepsy was mainly temporal (four right temporal mesial, four bitemporal, two left temporal lateral, one right temporal lateral, and one right temporal "plus"). Seven patients had negative magnetic resonance imaging. Whole-brain statistical analysis of PET imaging was performed at the voxel level, showing that in comparison to healthy subjects and to epileptic patients without IA, a hypometabolism in the right posterior insula characterized epileptic patients with IA. Our study suggests involvement of the right posterior insula-a part of the central autonomic network-in the pathophysiological mechanism of IA.

Interictal 18F-FDG brain PET metabolism in patients with postictal EEG suppression.

OBJECTIVE: Postictal generalized suppression (PGES) may be associated with SUDEP risk. We aimed to study metabolic changes on 18Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with focal to bilateral (generalized) seizures (GTCS) and PGES on stereoelectroencephalography (SEEG). METHODS: We analyzed interictal brain metabolism in a group of 19 patients with widespread postictal suppression (PGES+) associated with SEEG-recorded GTCS. This group was compared to 25 patients without widespread suppression (PGES-) as defined by SEEG, matched for epilepsy localization and lateralization. Frequency of GTCS was observed to be higher in the PGES+ group (high risk group for SUDEP). Analysis of metabolic data was performed by statistical parametric mapping (SPM) on the whole-brain, and principal component analysis (PCA) on AAL (automated anatomical labeling) atlas. RESULTS: Statistical parametric mapping showed right temporal pole hypometabolism in the PGES+ group (T-score = 3.90; p < 0.001; k = 185), in comparison to the PGES- group. Principal component analysis showed association between the metabolic values of certain regions of interest and PGES+/PGES- groups, confirmed by a significant difference (p < 0.05) in the values of the right dorsal temporal pole and of the left temporal pole between the two groups. Principal component analysis showed two dimensions significantly related to the PGES+/PGES- partition, involving the following regions: right temporal pole, right parahippocampal gyrus, right Rolandic operculum, bilateral paracentral lobule, right precuneus, right thalamus, right caudate and pallidum, bilateral cerebellum, left temporal pole, left Heschl's gyrus, left calcarine region, and left caudate, with loss of connection in PGES+ patients. Metabolic differences were independent of epilepsy localization and lateralization and persisted after correction for GTCS frequency. SIGNIFICANCE: Interictal metabolic changes within a predominantly right-sided network involving temporal lobe and connected cortical and subcortical structures were seen in patients with frequent GTCS presenting widespread postictal suppression.

The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol.

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot's targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim's circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.