Fluorodeoxyglucose Positron Emission Tomography Studies Research Articles

Different associations between amyloid-βeta 42, amyloid-βeta 40, and amyloid-βeta 42/40 with soluble phosphorylated-tau and disease burden in Alzheimer’s disease: a cerebrospinal fluid and fluorodeoxyglucose-positron emission tomography study

BackgroundDespite the high sensitivity of cerebrospinal fluid (CSF) amyloid beta (Aβ)42 to detect amyloid pathology, the Aβ42/Aβ40 ratio (amyR) better estimates amyloid load, with higher specificity for Alzheimer’s disease (AD). However, whether Aβ42 and amyR have different meanings and whether Aβ40 represents more than an Aβ42-corrective factor remain to be clarified. Our study aimed to compare the ability of Aβ42 and amyR to detect AD pathology in terms of p-tau/Aβ42 ratio and brain glucose metabolic patterns using fluorodeoxyglucose-positron emission tomography (FDG-PET).MethodsCSF biomarkers were analyzed with EUROIMMUN ELISA. We included 163 patients showing pathological CSF Aβ42 and normal p-tau (A + T − = 98) or pathological p-tau levels (A + T + = 65) and 36 control subjects (A − T −). A + T − patients were further stratified into those with normal (CSFAβ42 + /amyR − = 46) and pathological amyR (CSFAβ42 + /amyR + = 52). We used two distinct cut-offs to determine pathological values of p-tau/Aβ42: (1) ≥ 0.086 and (2) ≥ 0.122. FDG-PET patterns were evaluated in a subsample of patients (n = 46) and compared to 24 controls.ResultsCSF Aβ40 levels were the lowest in A − T − and in CSFAβ42 + /amyR − , higher in CSFAβ42 + /amyR + and highest in A + T + (F = 50.75; p < 0.001), resembling CSF levels of p-tau (F = 192; p < 0.001). We found a positive association between Aβ40 and p-tau in A − T − (β = 0.58; p < 0.001), CSFAβ42 + /amyR − (β = 0.47; p < 0.001), and CSFAβ42 + /amyR + patients (β = 0.48; p < 0.001) but not in A + T + . Investigating biomarker changes as a function of amyR, we observed a weak variation in CSF p-tau (+ 2 z-scores) and Aβ40 (+ 0.8 z-scores) in the normal amyR range, becoming steeper over the pathological threshold of amyR (p-tau: + 5 z-scores, Aβ40: + 4.5 z-score). CSFAβ42 + /amyR + patients showed a significantly higher probability of having pathological p-tau/Aβ42 than CSFAβ42 + /amyR − (cut-off ≥ 0.086: OR 23.3; cut-off ≥ 0.122: OR 8.8), which however still showed pathological values of p-tau/Aβ42 in some cases (cut-off ≥ 0.086: 35.7%; cut-off ≥ 0.122: 17.3%) unlike A − T − . Accordingly, we found reduced FDG metabolism in the temporoparietal regions of CSFAβ42 + /amyR − compared to controls, and further reduction in frontal areas in CSFAβ42 + /amyR + , like in A + T + .ConclusionsPathological p-tau/Aβ42 and FDG hypometabolism typical of AD can be found in patients with decreased CSF Aβ42 levels alone. AmyR positivity, associated with higher Aβ40 levels, is accompanied by higher CSF p-tau and widespread FDG hypometabolism.

Longitudinal brain and skeletal muscle FDG-PET changes in people with stiff person syndrome spectrum disorders (P4-5.021)

<h3>Objective:</h3> To describe changes in fluorodeoxyglucose positron emission tomography (FDG-PET) findings in the brain and muscles of individuals with stiff person syndrome spectrum disorders (SPSD) longitudinally. <h3>Background:</h3> SPSD includes multiple clinical phenotypes that rarely can be paraneoplastic in origin. An FDG-PET scan is frequently obtained as part of the malignancy work-up, and abnormal metabolic activity unrelated to malignancy has been shown to occur in both the brain and skeletal muscles of patients with SPSD. However, it is unclear if such findings persist or change over time. <h3>Design/Methods:</h3> A retrospective study was performed of patients with SPSD who were seen at Johns Hopkins SPS Center from 2009 to March 2022, with at least two FDG-PET studies in the medical record with source images of sufficient quality for comparison. Quantitative data was extracted from dedicated brain FDG-PET scans using NeuroQ™, which calculates Z-scores of 47 brain regions compared to healthy controls. Body FDG-PET scans will be reviewed qualitatively by a blinded nuclear medicine radiologist to detect the presence and pattern of hypermetabolism in skeletal muscle. Patients’ clinical characteristics, including type of treatment, will be correlated with PET data. <h3>Results:</h3> Out of 98 SPSD patients who underwent an FDG-PET scan, 10 were identified that met inclusion criteria. Median age at time of SPSD onset was 51±15.8 years, 60% were males, and 60% were black. Mean duration from symptom onset to first FDG-PET scan was 0.78±0.62 years. The majority of patients had SPS-plus phenotype. All patients were seropositive for an SPSD-associated antibody and received an immune therapy. Preliminary data demonstrate that all patients had at least 1 region of dysmetabolism on initial brain scan, and at least 3 regions on follow-up. <h3>Conclusions:</h3> We will present longitudinal metabolic changes in brain and body FDG-PET scans of patients with SPSD, and determine if any changes observed are associated with clinical characteristics. <b>Disclosure:</b> Dr. Roman has nothing to disclose. The institution of Dr. Wang has received research support from Genentech. Dr. Sadaghiani has nothing to disclose. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Newsome has received research support from Biogen. The institution of Dr. Newsome has received research support from Genentech/Roche. The institution of Dr. Newsome has received research support from Department of Defense. The institution of Dr. Newsome has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Newsome has received research support from National MS Society. The institution of Dr. Newsome has received research support from The Stiff Person Syndrome Research Foundation. Dr. Newsome has received personal compensation in the range of $5,000-$9,999 for serving as a Clinical adjudication committee member for clinical trial with medDay Pharmaceuticals. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving as a Lead PI for Clinical Trial with Roche.

Task-evoked simultaneous FDG-PET and fMRI data for measurement of neural metabolism in the human visual cortex

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18–49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics.

Cognitive reserve hypothesis in frontotemporal dementia: A FDG-PET study

Background and objectiveReserve is defined as the ability to maintain cognitive functions relatively well at a given level of pathology. Early life experiences such as education are associated with lower dementia risk in general. However, whether more years of education guards against the impact of brain alterations also in frontotemporal dementia (FTD) has not been shown in a large patient collective. Therefore, we assessed whether education is associated with relatively high cognitive performance despite the presence of [18F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET) hypometabolism in FTD. MethodsSixty-six FTD subjects (age 67 ± 8 years) and twenty-four cognitively healthy controls (HC) were evaluated. Brain regions with FTD-related glucose hypometabolism in the contrast against HC and brain regions that correlate with the cognitive function were defined by a voxel-based analysis and individual FDG-PET values were extracted from all frontotemporal brain areas. Linear regression analysis served to test if education is associated with residualized cognitive performance and regional FDG-PET hypometabolism after controlling for global cognition. ResultsCompared to healthy controls, patients with FTD showed glucose hypometabolism in bilateral frontal and temporal brain areas whereas cognition was only associated with deteriorated glucose metabolism in the left temporal lobe. The education level was significantly correlated with the residualized cognitive performance (residuals from regression analysis between hypometabolism and cognitive function as a quantitative index of reserve) and also negatively correlated with left temporal FDG-PET hypometabolism after controlling for cognition. ConclusionsIn patients with FTD, the education level predicts the existing left temporal FDG-PET hypometabolism at the same cognition level, supporting the cognitive reserve hypothesis in FTD.

Predictors of Myocardial Ischemia in Preoperative Oncology Patients Who Underwent Fluorodeoxyglucose-Positron Emission Tomography Study.

Background:Coronary artery calcification (CAC) can be visually estimated on computed tomography (CT) attenuation correction (CTAC) of positron emission tomography (PET). The visual estimation of CAC from CTAC scans performed for PET/CT is comparable to the standard CAC score scan. Myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) is commonly performed for risk stratification before oncologic surgery.Objective:We investigated the value of visual estimation of CAC from CTAC of PET/CT as well as other factors such as coronary artery disease (CAD) risk factors and type of cancer as predictors of MPI ischemia.Methods:Retrospectively, we identified 268 patients who underwent PET/CT and MPI for preoperative cardiac evaluation. Visual estimation of CAC was performed and classified into four categories.Results:The results of visual CAC were as follows: 47.8% – zero CAC, 32.8% – mild CAC, 14.2% – moderate CAC, and 5.2% – severe CAC. The majority of patients (85.8%) had normal MPI, whereas 14.2% were abnormal. There was a strong association between ischemia on MPI and CAC seen on CTAC (P < 0.01), dyslipidemia (P < 0.01), family history of CAD (P < 0.05), smoking (P < 0.01), and type of malignancy (P < 0.01).Conclusion:A strong association exists between visual estimation of CAC on CTAC and MPI. Zero is highly associated with normal MPI, but moderate-to-severe CAC is associated with abnormal MPI, in addition smoking, dyslipidemia, and certain cancer are associated with ischemic MPI; subsequently, preoperative cardiac testing is warranted in these subsets of patients.

Brain Plasticity and Neurophysiological Correlates of Meditation in Long-Term Meditators: A 18Fluorodeoxyglucose Positron Emission Tomography Study Based on an Innovative Methodology.

Objective: Previous studies evaluating neurophysiological correlates of long-term meditation are constrained by some methodological limitations. The objective of this study was to measure changes in the regional cerebral glucose metabolism during meditation using a novel methodological approach. Design: The present study was a part of a larger, nonrandomized, single-center open-label study. Setting/location: The study was conducted at the Department of Physiology and Department of Nuclear Medicine and Positron Emission Tomography. A dedicated place was set up as a yoga room, away from the positron emission tomography (PET) scanning room in the Department of Nuclear Medicine and Positron Emission Tomography, where meditators performed meditation in a peaceful environment in a sitting posture with eyes closed. The electroencephalography (EEG) was recorded to affirm the meditation objectively. Subjects: Twenty-four sets of PET scans were obtained at 2 different occasions (baseline and postmeditation within 40 min of 18FDG [18fluorodeoxyglucose] injection) from 12 apparently healthy, male, right-handed long-term meditators practicing Preksha meditation (since >5 years, at least 5 days a week) who were recruited from a well-established meditation center in Delhi. Outcome measures: Changes in the regional cerebral glucose metabolism during meditation versus baseline. Results: Regional cluster analysis showed significantly activated well-defined areas of fronto-parieto-temporal regions of the right versus left hemisphere during meditation. Interestingly, right homolog of Broca's area and right lentiform nucleus were hyperactive during meditation in all the meditators. Conclusions: Long-term meditation might potentially enhance the explicit functions of specific parts of the right hemisphere, possibly due to neuroplastic changes in the brain. Importantly, results of the current study are encouraging and show a novel methodological approach to acquire 18FDG PET/CT (computed tomography) images. The study was registered at Clinical Trial Registry India (CTRI), CTRI/2009/091/000727.

18F]fluorodeoxyglucose-positron emission tomography study of genetically confirmed patients with Dravet syndrome

ObjectiveTo understand cerebral brain dysfunction in patients with Dravet syndrome (DS), we conducted a [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) study in patients with DS whose SCN1A gene variant was confirmed. MethodsFDG-PET was performed on eight patients with DS. A SCN1A mutation analysis revealed missense variants in four patients and truncation variants in four patients. The patients’ ages at the time of the PET study were 2, 2, 2, 3, 6, 13, 20, and 29 years old, respectively. The patients’ developmental/intelligence quotient at the time of the PET study were 62, 52, 64, 35, 30, 15, and <25, respectively. The mean standardized uptake value (SUV) was calculated in four segments (frontal, temporal, parietal, and occipital) for the semi-quantitative analysis of 18F-FDG uptake. This value represents the average of the regions of interest in each lobe and was divided by the average SUV of the cerebellar hemisphere of each patient and compared between the patients with DS and the diseased controls. ResultsGlucose uptake in patients with DS decreased significantly, particularly in those ≥6 years old. Importantly, a comparison between the younger and older patients with DS revealed that glucose uptake was normal in patients who were ≤3 years (2, 2, 2, and 3 years), whereas a profound reduction in glucose uptake in the fronto-temporo-parietal-occipital cortices was observed in patients ≥ 6 years (6, 13, 20, and 29 years). Magnetic resonance imaging revealed no detectable atrophic legions or other changes in the cerebral cortices of patients ≥ 6 years of age. SignificanceThe present study showed a remarkable reduction in cerebral glucose metabolism in multiple lobes for the first time, which became obvious after the late infantile period. These findings may indicate a functional neuroimaging aspect of epileptic encephalopathy of DS or a feature of the SCN1A variant itself.

The relationship between structural MRI, FDG-PET, and memory in temporal lobe epilepsy: Preliminary results

Structural and metabolic abnormalities of the temporal lobe are frequently found in temporal lobe epilepsy (TLE). In the present retrospective study, we investigated whether structural abnormalities evident in magnetic resonance imaging (MRI) and hypometabolism evident in [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) independently influence verbal and nonverbal learning and delayed memory in patients with TLE. Sixty-eight patients with refractory unilateral TLE (35 left TLE, 33 right TLE) were divided into three groups: (1) no evidence of pathology in either MRI or FDG-PET studies (MRI−/PET−, n=15), (2) temporal FDG-PET determined hypometabolism with normal MRI findings (MRI−/PET+, n=21), and (3) evidence of temporal abnormalities in both MRI and FDG-PET studies (MRI+/PET+, n=32). A fourth group (MRI+/PET−, n=4) was too small for further statistical analysis and could not be included. Patients with MRI+/PET+ showed worse verbal memory than patients with MRI−/PET− (p<0.01), regardless of side of seizure focus. Verbal memory performance of patients with MRI−/PET+ was located between patients with MRI+/PET+ and MRI−/PET−, although group differences did not achieve statistical significance (ps>0.1). No group differences were found for nonverbal memory (p=0.27). Our results may suggest an interactive negative effect of metabolic and structural temporal lobe abnormalities on verbal memory. Still, our results are preliminary and need further validation by studies involving larger patient groups and up-to date quantitative imaging analysis methods.

Learning Metabolic Brain Networks in MCI and AD by Robustness and Leave-One-Out Analysis: An FDG-PET Study.

This study attempted to better understand the properties associated with the metabolic brain network in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Graph theory was employed to investigate the topological organization of metabolic brain network among 86 patients with MCI, 89 patients with AD, and 97 normal controls (NCs) using 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) data. The whole brain was divided into 82 areas by Brodmann atlas to construct networks. We found that MCI and AD showed a loss of small-world properties and topological aberrations, and MCI showed an intermediate measurement between NC and AD. The networks of MCI and AD were vulnerable to attacks resulting from the altered topological pattern. Furthermore, individual contributions were correlated with Mini-Mental State Examination and Clinical Dementia Rating. The present study indicated that the topological patterns of the metabolic networks were aberrant in patients with MCI and AD, which may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI and AD.

Glucose Deficiency Elevates Acid-Sensing Ion Channel 2a Expression and Increases Seizure Susceptibility in Temporal Lobe Epilepsy

Brain hypometabolism is a common epilepsy-related finding in both patients and animal models. Fluorodeoxyglucose positron emission tomography studies have shown that recurrent seizures lead to reduced glucose metabolism in certain brain regions, but no studies have definitively determined whether this induces epileptogenesis. There is evidence that acid-sensing ion channel 2a (ASIC2a) affects epilepsy susceptibility. Transcription factor CP2 (TFCP2) regulates ASIC2a expression. We report that suppressed TFCP2 expression and elevated ASIC2a expression were associated with glucose hypometabolism in the hippocampi of humans with epilepsy and of rat epilepsy model brains. In cultured PC12 cells, we determined that glucose deficiency led to TFCP2 downregulating ASIC2a. Moreover, electrophysiological recordings from cultured rat hippocampal slices showed that ASIC2a overexpression resulted in more action potentials in CA1 pyramidal neurons and increased seizure susceptibility. Our findings suggest that hippocampal glucose hypometabolism elevates ASIC2a expression by suppressing TFCP2 expression, which further enhances the intrinsic excitability of CA1 pyramidal neurons and increases seizure susceptibility in patients with temporal lobe epilepsy.

Regional glucose hypometabolic spread within the primary motor cortex is associated with amyotrophic lateral sclerosis disease progression: A fluoro-deoxyglucose positron emission tomography study.

ObjectiveHere we investigate the process of neurodegeneration in amyotrophic lateral sclerosis (ALS). The relationship between the cortical field spreading of glucose metabolic decreases in the primary motor cortex (PMC) and the progression of corresponding extremity dysfunction was evaluated using [18F] fluoro-deoxyglucose (FDG)-positron emission tomography (PET).MethodsPatients with ALS underwent [18F] FDG-PET and the resulting datasets were individually contrasted against healthy controls using the NEUROSTAT software. The extent ratio was defined as the proportion of pixels with a significant Z-score decrease within regions of the primary motor cortex (precentral gyrus or paracentral lobule) opposite to the impaired upper extremities (UEs) or lower extremities (LEs), respectively. Clinical symptoms in all extremities were assessed using an upper motor neuron (UMN) score and the MRC (Medical Research Council) sum score upon physical examination. Cross-sectional correlations were analysed between clinical symptoms, the duration of these symptoms, and the extent ratio.ResultsNineteen regions of the primary motor cortex corresponding to symptomatic limb in 10 participants were evaluated. In the corresponding region of the primary motor cortex, the extent ratio increased (same meaning as hypometabolic area spread) in association with symptom duration (rs = 0.5, p = 0.03). Neither UMN nor lower motor neuron (LMN) scores were correlated with symptom duration. Three out of 19 impaired regions did not show upper motor neuron (UMN) signs upon physical examination. The extent ratio and UMN score-controlled symptom duration were partially correlated (rs = 0.5, p = 0.05).ConclusionsIn patients with ALS, glucose metabolism decreased in the impaired side of the primary motor cortex depending on the clinical symptom progression in the corresponding extremities, regardless of the presence of clinical UMN signs. A decrement in glucose metabolism on FDG-PET corresponding to symptoms in the primary motor cortex might be an indicator of the time-dependent course of ALS neurodegeneration.

PET and MRI detection of early and progressive neurodegeneration in spinocerebellar ataxia type 36.

The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans. Twenty SCA36 patients underwent a study consisting of FDG-PET and MRI scans. Clinical motor evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA). FDG-PET was carried out using a voxel-by-voxel and region-of-interest analysis. MRI evaluation was based on visual inspection and volumetric analysis. SARA ranged from 0 to 24.5 (4 patients asymptomatic, 3 with unspecific symptoms, and 13 with cerebellar signs). FDG-PET revealed hypometabolism in the asymptomatic stage in the vermis and right cerebellar hemisphere. In the ataxic stage, hypometabolism spread to both cerebellar hemispheres and the brain stem. MRI was normal in asymptomatic and preataxic individuals and showed superior cerebellar vermis atrophy early in the ataxic stage, diffuse cerebellar atrophy some years into the disease course, and a pattern of olivopontocerebellar atrophy in the oldest patients. There was no significant cerebellar atrophy in patients younger than 50 years. We present the first FDG-PET study of SCA36 and one of the largest neuroimaging study of SCAs. Our results revealed neuronal dysfunctions in the vermis and right cerebellar hemisphere as soon as a decade before the onset of motor symptoms. In the ataxic stage, dysfunctions spread to both hemispheres and the brain stem. © 2016 International Parkinson and Movement Disorder Society.

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately.

FDG-PET study of patients with Leigh syndrome

We conducted a [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) study in five patients (median age 11 (range 4–13) years) with Leigh syndrome to evaluate its usefulness for understanding the functional brain dysfunction in this disease and in future drug trials. Four patients were found to have reported mitochondrial DNA gene mutations. The brain T2-weighted magnetic resonance imaging (MRI) showed high-intensity areas in the putamen bilaterally in five patients, caudate bilaterally in four, thalamus bilaterally in two, and brainstem in one. Cerebellar atrophy was observed in older two patients. For disease control, seven age-matched epilepsy patients who had normal MRI and FDG-PET studies were selected. For semiquantitative analysis of the lesions with decreased 18F-FDG uptake, the mean standard uptake value (SUV) was calculated in regions of interest (ROIs) placed in each brain structure. We compared the SUV of nine segments (the frontal, temporal, parietal, and occipital lobes, thalami, basal ganglia, mid-brain, pons, and cerebellum) between patients with Leigh syndrome and controls. The glucose uptake was decreased significantly in the cerebellum and basal ganglia, which could explain the ataxia and dystonia in patients with Leigh syndrome. Although this study had some limitations, FDG-PET might be useful for evaluating the brain dysfunction and treatment efficacy of new drugs in patients with Leigh syndrome. Further study with more patients using advanced methods to quantify glucose uptake is needed before drawing a conclusion.

Transcutaneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data.

So far, among the different non-invasive neurostimulation methods, only transcutaneous supraorbital nerve stimulation (t-SNS) with the Cefaly® (Cefaly Technology sprl, Herstal, Belgium) device has randomized controlled trial-based evidence for safety and efficacy and obtained American Food and Drug Administration approval for the prevention of episodic migraine. In a double-blinded, randomized, sham-controlled trial on 67 episodic migraine patients (mean pre-treatment migraine days/month: 6.9), the 50% responder rate after 3 months was significantly higher in the active group (38.2%) than in the sham group (12.1%); attack frequency and total headache days were also significantly reduced, but not headache severity. Acute anti-migraine drug intake was reduced by 36.7% in the active group. Statistical sub-analysis suggested that t-SNS was more effective in patients with a higher attack frequency. In a large survey on 2313 Cefaly users about safety and satisfaction only 4.3% of subjects reported side effects, all of which were minor and fully reversible, the most frequent being intolerance to the paresthesia feeling and the most severe an allergic skin reaction to the electrode gel. The efficacy/safety ratio of the Cefaly device was therefore most favorable, especially when compared to preventive anti-migraine drugs. The therapeutic efficacy of t-SNS with Cefaly with low-frequency migraine (≤5 attacks/month) was recently confirmed in an open randomized trial. No published data are available in chronic migraine. According to preliminary results of a fluorodeoxyglucose-positron emission tomography study, Cefaly might exert its effect in migraine by increasing activity in crucial areas of the limbic system and salience matrix such as orbitofrontal and anterior cingulate cortices.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-015-0039-5) contains supplementary material, which is available to authorized users.

Accuracy of arterial spin labeling magnetic resonance imaging (MRI) perfusion in detecting the epileptogenic zone in patients with drug‐resistant neocortical epilepsy: comparison with electrophysiological data, structural MRI, SISCOM and FDG‐PET

Locating the epileptogenic zone (EZ) in patients with neocortical epilepsy presents major challenges. Our aim was to assess the accuracy of arterial spin labeling (ASL), an emerging non-invasive magnetic resonance imaging (MRI) perfusion technique, to locate the EZ in patients with drug-resistant neocortical epilepsy. Twenty-five consecutive patients with neocortical epilepsy referred to our epilepsy unit for pre-surgical evaluation underwent a standardized assessment including video-electroencephalography (EEG) monitoring, structural MRI, subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) and fluorodeoxyglucose positron emission tomography (FDG-PET) studies. An ASL sequence was included in the MRI studies. Areas of hypoperfusion or hyperperfusion on ASL were classified into 15 anatomic-functional cortical regions; these regional cerebral blood flow maps were compared with the EZ determined by the other tests and the strength of concordance was assessed with the kappa coefficient. Of the 25 patients [16 (64%) women; mean age 32.4 (±13.8) years], 18 (72%) had lesions on structural MRI. ASL abnormalities were seen in 15 (60%) patients (nine hypoperfusion, six hyperperfusion). ASL had a very good concordance with FDG-PET (k = 0.84), a good concordance with structural MRI (k = 0.76), a moderate concordance with video-EEG monitoring (k = 0.53) and a fair concordance with SISCOM (k = 0.28). Arterial spin labeling might help to confirm the location and extent of the EZ in the pre-surgical workup of patients with drug-resistant neocortical epilepsy.

Topography of primitive reflexes in dementia: an F-18 fluorodeoxyglucose positron emission tomography study.

Although primitive reflexes (PRs) are inhibited during the first years of childhood, they may reappear with brain injury. PRs have been linked to frontal lobe dysfunction, but their precise topography has not yet been defined. The purpose of this study was to map which regions of the brain display a reduced glucose metabolism in patients with cognitive impairment and PRs. A prospective study was conducted to evaluate PRs in a group of patients assessed due to suspected cognitive decline. Neurological and neuropsychological examinations and (18) F-fluorodeoxyglucose positron emission tomography fused with computerized tomography were performed. Voxel-based brain mapping analysis by means of statistical parametric mapping was used to compare patients with and without PRs. The study included 99 patients (33 diagnosed with Alzheimer's disease, 33 on the frontotemporal dementia spectrum and 33 with other diagnoses). Mean age was 71±9.7years; time since symptom onset was 3.6±2.9years. At least one PR was observed in 43 cases (43.4% of the whole sample; 48.5% in the Alzheimer disease group, 63.6% in frontotemporal dementia and 18.2% in the group with other diagnoses). The group of patients with PRs exhibited a decreased cerebral metabolism in the bilateral superior frontal gyri (Brodmann area 6), bilateral putamina and thalami. The presence of PRs was associated with hypometabolism at the superior frontal gyrus and putamen. This suggests that dysfunction in the corticostriatal motor circuit (supplementary motor area-putamen-thalamus) may constitute the anatomical basis of the recurrence of PRs.

Functional neuroimaging findings in patients with lateral and mesio-lateral temporal lobe epilepsy; FDG-PET and ictal SPECT studies.

The differentiation of combined mesial and lateral temporal onset of seizures (mesio-lateral TLE, MLTLE) from lateral TLE (LTLE) is critical to achieve good surgical outcomes. However, the functional neuroimaging features in LTLE patients based on the ictal onset zone utilizing intracranial EEG (iEEG) in a large series have not been investigated. We enrolled patients diagnosed with MLTLE (n = 35) and LTLE (n = 53) based on the site of ictal onset zone from iEEG monitoring. MLTLE is defined when ictal discharges originate from the mesial and lateral temporal cortices independently, whereas seizures of LTLE arise exclusively from the lateral temporal cortex. Compared to patients with LTLE, patients with MLTLE were more likely to have 18F- fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism and hyperperfusion on ictal single-photon emission computed tomography (SPECT) restricted to the temporal areas. MLTLE patients had more frequent aura or secondarily generalized seizures than LTLE patients. No significant differences were found in scalp EEG, MRI, and Wada asymmetry between groups. The overall seizure-free rate was good (73.8%, mean follow-up = 9.7 years), which was not different (Engel class I, 74.3% in MLTLE vs. 73.6% in LTLE). Postsurgical memory function was spared in LTLE patients, while visual memory was impaired in MLTLE patients when their mesial temporal structures were sufficiently resected. It suggests that functional neuroimaging (interictal PET and ictal and interictal SPECT) may play a crucial role to differentiate between MLTLE and LTLE.

Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease: A FDG-PET Study.

We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD.

F-18 fluorodeoxyglucose positron emission tomography study of impaired emotion processing in first episode schizophrenia

BackgroundSchizophrenia cases have been consistently shown to have behavioural and neurofunctional abnormalities but studies during early course are scarce. The present work assesses the performance of acute first episode schizophrenia cases on correlation of a facial emotion perception task with brain function using fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). MethodsTwenty First episode schizophrenia cases and 20 matched healthy controls living in the community were enrolled. For cases, longest duration of illness was one year and treatment with neuroleptic did not exceed two weeks on the day of scan. To measure facial emotion perception (FEP) both groups were administered the Emotion battery from the Penn Computerized Battery followed by PET acquisition. SPM 8 analysis for group differences at p<0.001 was performed. ResultsSchizophrenia subjects showed hypoactivation of bilateral prefrontal cortices and fusiform gyrii, with significant hyperactivation of bilateral basal ganglia and left precuneus. Positive correlation of metabolism in prefrontal cortex and performance indices on emotions domain was seen. No correlation of chlorpromazine equivalent days with metabolism in basal ganglia was observed. ConclusionsThe performance of schizophrenia cases on FEP task was significantly impaired in comparison to the control group. Brain regions implicated in emotion processing showed hypometabolism in cases as compared to controls. Failure of schizophrenia cases to optimally recruit brain circuitry may be contributing to deficits on FEP task. These findings suggest inherent deficits in neural circuitry of emotion processing in schizophrenia; devoid of confounding effects of neuroleptics and duration of illness.