Cortical Hypometabolism Research Articles

Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer’s disease

Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer’s disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairment and dementia) from the longitudinal multi-center observational ADNI cohort. Participants were on average 75 years of age (SD = 7.89), 40.8% were female, 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD-LB+), 395 (49.7%) had only AD pathology (AD+LB-), and 177 (22.3%) had both pathologies (AD+LB+). The AD+LB+ group showed worst baseline performance for most cognitive outcomes and compared to the AD+LB− group faster global cognitive decline and more cortical hypometabolism, particularly in posterior brain regions. Neuropathological examination (n = 61) showed high sensitivity (26/27, 96.3%) and specificity (27/28, 96.4%) of the SAA-test. We showed that co-existing LB-positivity exacerbates cognitive decline and cortical brain hypometabolism in AD. In vivo LB pathology detection could enhance prognostic evaluations in clinical practice and could have implications for clinical AD trial design.

18F-FDG brain PET: a metabolic predictive factor for gait improvement after cerebrospinal fluid shunting in normal pressure hydrocephalus?

The pathophysiology of normal pressure hydrocephalus (NPH) has not been fully elucidated. Treating NPH with cerebrospinal fluid shunts to improve gait disturbances may have some risks and inconsistent benefits. No clear predictive factor has been identified thus far. This preliminary study aimed to evaluate the predictive value of preoperative brain 18F-FDG positron emission tomography (PET) on overall gait response in patients with NPH. Sixteen patients with NPH who underwent 18F-FDG PET before shunt surgery between 2012 and 2022 were included retrospectively and separated into two groups based on their gait response one year after surgery: responders (R) or nonresponders (NR). Brain glucose metabolism was assessed using visual and semiquantitative analyses using SPM8 software (Welcome Department of Cognitive Neurology, University College, London, UK). Five regions of interest were selected: global cortex, cerebellum, thalamus, striatum, and midbrain. Visual interpretation showed more frequent hypometabolism of the striatum, thalamus and global cortex in NR. None of the patients showing hypometabolism of these regions were R. Based on these results, the visual interpretation allowed us to identify 3/8 NR and 8/8 R. Semiquantitative analysis confirmed significantly lower thalamic metabolism in the NR group (P=0.037) and a trend towards lower metabolism of the striatum (P=0.075) with an area under the curve of 0.77 for thalamic metabolism to discriminate between R and NR. This preliminary study using brain 18F-FDG PET suggests that reduced brain metabolism in the thalamus and striatum along with cortical hypometabolism may be associated with poorer gait response to CSF shunting in normal pressure hydrocephalus (NPH). Although these findings suggest that preoperative brain 18F-FDG PET could potentially aid in selecting appropriate candidates for shunt surgery, further research with larger sample sizes is needed to confirm these results.

The clinical and predictive value of 18F-FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis.

To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

The diagnostic and prognostic value of tau-PET in amnestic MCI with different FDG-PET subtypes.

Mild cognitive impairment presenting with an amnestic syndrome (aMCI) and amyloid positivity is considered due to AD. Many subjects, however, can show an overall very slow progression relevant for differential diagnosis, prognosis, and treatment. This study assessed PET biomarkers, includingbrain glucose metabolism, tau, and amyloid load, in a series of comparable aMCI at baseline, clinically evaluated at follow-up. We included 72 aMCI subjects from Geneva Memory Center (N = 31) and ADNI cohorts (N = 41), selected based on available FDG-PET, tau-PET, amyloid-PET, and clinical follow-up (2.3 years ± 1.2). A data-driven algorithm classified brain metabolic patterns into subtypes that were then compared for clinical and PET biomarker measures and cognitive decline. Voxel-wise comparisons were performed both with FDG-PET and tau-PET data. The algorithm classified three metabolic subtypes, namely "Hippocampal-sparing with cortical hypometabolism" (Type1; N = 27), "Hippocampal and cortical hypometabolism" (Type 2; N = 23), and "Medial temporal hypometabolism" (Type 3; N = 22). Amyloid positivity and tau accumulation in the medial temporal and neocortical regions characterized Type 1 and Type 2, whereas Type 3 showed no significant tau pathology, variable amyloid positivity, and stability at follow-up. All tau-positive patients, independently of the FDG-based subtype, showed faster cognitive decline. aMCI subjects can differ in metabolic patterns, tau and amyloid pathology, and clinical progression. Here, we complemented with PET tau biomarker the specific brain hypometabolic patterns at the individual level in the prodromal phase, contributing to the patient's classification. Tau PET is the most accurate biomarker in supporting or excluding the AD diagnosis in aMCI across metabolic subtypes and also predicting the risk of decline.

The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia

BackgroundBased on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI).MethodsWe included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer’s disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration.ResultsThe clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL.ConclusionsOur finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

A ROI-based quantitative pipeline for 18F-FDG PET metabolism and pCASL perfusion joint analysis: Validation of the 18F-FDG PET line

In Mild Cognitive Impairment (MCI), the study of brain metabolism, provided by 18F-FluoroDeoxyGlucose Positron Emission Tomography (18F-FDG PET) can be integrated with brain perfusion through pseudo-Continuous Arterial Spin Labeling Magnetic Resonance sequences (MR pCASL). Cortical hypometabolism identification generally relies on wide control group datasets; pCASL control groups are instead not publicly available yet, due to lack of standardization in the acquisition parameters. This study presents a quantitative pipeline to be applied to PET and pCASL data to coherently analyze metabolism and perfusion inside 16 matching cortical regions of interest (ROIs) derived from the AAL3 atlas. The PET line is tuned on 36 MCI patients and 107 healthy control subjects, to agree in identifying hypometabolic regions with clinical reference methods (visual analysis supported by a vendor tool and Statistical Parametric Mapping, SPM, with two parametrizations here identified as SPM-A and SPM-B). The analysis was conducted for each ROI separately. The proposed PET analysis pipeline obtained accuracy 78 % and Cohen's к 60 % vs visual analysis, accuracy 79 % and Cohen's к 58 % vs SPM-A, accuracy 77 % and Cohen's к 54 % vs SPM-B. Cohen's к resulted not significantly different from SPM-A and SPM-B Cohen's к when assuming visual analysis as reference method (p-value 0.61 and 0.31 respectively). Considering SPM-A as reference method, Cohen's к is not significantly different from SPM-B Cohen's к as well (p-value = 1.00). The complete PET-pCASL pipeline was then preliminarily applied on 5 MCI patients and metabolism-perfusion regional correlations were assessed. The proposed approach can be considered as a promising tool for PET-pCASL joint analyses in MCI, even in the absence of a pCASL control group, to perform metabolism-perfusion regional correlation studies, and to assess and compare perfusion in hypometabolic or normo-metabolic areas.

Striatal Amyloid deposition in sporadic Alzheimer’s Disease

AbstractBackgroundIt has been shown that disorders associated with early‐life alterations in amyloid production or processing such as in autosomal dominant Alzheimer’s disease (AD) and down syndrome‐associated dementia have a different pattern of Aβ deposition, with early striatal accumulation, as compared to sporadic late‐onset cases, in which striatal deposition has been suggested to be a marker of late and advanced amyloidosis. It is not clear, however, if the pattern of amyloid accumulation is related to any other factors or if it has any impact on brain metabolism. We aimed to determine if there are any clinical or demographic predictors of striatal tau accumulation in sporadic AD and whether its presence affects the subjects´ brain metabolism.MethodSubjects that underwent positron emission tomography (PET) scans with 18F‐FDG and 11C‐PIB were analyzed retrospectively. Only those with clinical diagnosis of AD and mild cognitive impairment (MCI) due to AD were considered for the analysis. Visual analyses were performed to exclude subjects without cortical amyloid accumulation. Mean values from cortical volumes of interest (VOIs) and striatum were obtained. Amyloid deposition was correlated with age and disease duration via Pearson’s correlations. Amyloid deposition was also correlated to brain metabolism as assessed by FDG PET.Result150 subjects were included in this study. Neither age nor disease duration was correlated with striatal amyloid accumulation. Subjects with striatal Pib accumulation showed higher cortical amyloid burden. Moreover, higher striatal amyloid burden was positively correlated with higher frontal amyloid burden specifically. Amyloid burden in the striatum did not seem to have an impact on the glucose metabolism in the striatum itself. However, variations in cortical glucose metabolism could be observed. A higher striatal amyloid burden was correlated with cortical glucose hypometabolism, specifically in the precuneus and temporal areas (Figure 1).ConclusionThere seems to be a stage of sporadic Alzheimer’s disease in which amyloid accumulates in the striatum. This, in turn, appears to have an impact on brain functioning. Whether this has a real impact on cognitive performance remains to be elucidated.

Monoaminergic Disfunctions and Misfolded Proteins levels in the Alzheimer’s Disease Continuum

AbstractBackgroundMonoaminergic systems are pharmacologically modulable and therefore both a target for symptomatic therapies and a window for the study of disease progression. Although these mechanisms are unclear. We explore the progression and the distribution of monoaminergic deficits in the Alzheimer’s Disease (AD) continuum, along with the accumulation of misfolded pathological proteins.MethodWe included 50 patients with Alzheimer’s Disease (AD) and 42 Healthy Controls (HC). We acquired brain [18F]FDG‐PET images as a marker of neurodegeneration and MMSE as a measure of global cognitive functioning. We performed voxel‐based analysis between AD vs. HC. Using JuSpace toolbox we explored the correlation between [18F]FDG‐PET images and PET maps of dopamine (DAT), serotonin (SERT), noradrenaline (NAT) and choline vesicular (VAChT) transporters cortical distribution. Moreover, we evaluated relative hypometabolism in the main cholinergic nucleus (Meynert nucleus). We divided in two groups the AD patients based on MMSE score (AD Dementia ‐ADD‐ &lt;24; MCI ≥24), to explore the association between monoaminergic disfunction and pathological proteins burden, across the AD continuum.ResultSample characteristics are provided in Table 1. Results from voxel‐based analysis are shown in Figure 1. In the whole AD group, the distribution of relative cortical hypometabolism was associated with a significant reduction of VAChT availability (p = 0.018). This association remained significant when considering the ADD (p = 0.006), but not the MCI group. Figure 2.β‐amyloid42 levels and β‐amyloid42/40 ratio were inversely correlated with VAChT in the ADD group (p = 0.003; p = 0.038, respectively). No correlation was observed in the MCI group. Lastly, there was no correlation between Meynert nucleus relative hypometabolism and misfolded proteins levels in all groups.ConclusionIn the ADD phase we showed a significant damage in the cortical regions targeted by the cholinergic system. This result was not evident among the other systems studied, nor in the MCI phase. This provides an explanation of the reduction of the cholinesterase inhibitors efficiency in the dementia phase. Moreover, we showed that β‐amyloid accumulation was not associated with Meynert Nucleus degeneration, but that impacted on cholinergic function via damage accumulation in the cortical areas targeted by the cholinergic system.

Brain hypometabolism in non-demented microtubule-associated protein tau H1 carriers with Parkinson's disease.

The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype. We compared a group of 26 H1/H1 and 20 H1/H2 carriers with late-onset PD. Participants underwent a comprehensive neuropsychological cognitive evaluation and a [18F]-Fluorodeoxyglucose PET-MR scan. MAPT H1/H1 carriers showed worse performance in the digit span forward test of attention compared to MAPT H1/H2 carriers. In the [18F]-Fluorodeoxyglucose PET comparisons, MAPT H1/H1 displayed hypometabolism in the frontal cortex, parahippocampal, and cingulate gyrus, as well as in the caudate and globus pallidus. PD patients MAPT H1/H1 carriers without dementia exhibit relative hypometabolism in several cortical areas as well as in the basal ganglia, and worse performance in attention than MAPT H1/H2 carriers. Longitudinal studies should assess if lower scores in attention and dysfunction in these areas are predictors of dementia in MAPT H1/H1 homozygotes.

Atypical brain FDG-PET patterns increase the risk of long-term cognitive and motor progression in Parkinson's disease

IntroductionBrain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. MethodsForty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models. ResultsParticipants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group. ConclusionThis study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level.

FDG-PET markers of heterogeneity and different risk of progression in amnestic MCI.

Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. We looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG-PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An algorithm based on FDG-PET hypometabolism classified each subject into subtypes, then compared biomarker measures and clinical progression. Three subtypes emerged:hippocampal sparing-cortical hypometabolism, associated with younger age and the highest level of Alzheimer's disease (AD)-CSF pathology;hippocampal/cortical hypometabolism, associated with a high percentage of APOE ε3/ε4 or ε4/ε4carriers;medial-temporal hypometabolism, characterized by older age, the lowest AD-CSF pathology, the most severe hippocampal atrophy, and a benign course. Within the whole cohort, the severity of temporo-parietal hypometabolism, correlated with AD-CSF pathology and marked the rate of progression of cognitive decline. FDG-PET can distinguish clinically comparable aMCI at single-subject level with different risk of progression to AD dementia or stability. The obtained results can be useful for the optimization of pharmacological trials and automated-classification models. Algorithm based on FDG-PET hypometabolism demonstrates distinct subtypes across aMCI; Three different subtypes show heterogeneous biological profiles and risk of progression; The cortical hypometabolism is associated with AD pathology and cognitive decline; MTL hypometabolism is associated with the lowest conversion rate and CSF-AD pathology.

Neurocognitive Profile and 18 F-Fluorodeoxyglucose Positron Emission Tomography Brain Imaging Correlation in Children with Electrical Status Epilepticus during Sleep.

Objective Electrical status epilepticus in sleep (ESES) is defined by near-continuous epileptiform discharges during sleep along with cognitive, behavioral, and/or imaging abnormalities. We studied the neurocognitive profile and their correlation with 18 F fluorodeoxyglucose positron emission tomography (FDG PET) brain abnormalities in children with ESES. Methods Fourteen children with ESES with normal magnetic resonance imaging (MRI) from March to December 2019 were included. The intelligence quotient (IQ) and child behavior checklist (CBCL) scores were estimated using validated scales, and FDG PET brain was done at the same point of time to look for cerebral metabolic defects which was compared with a control group. Results Fourteen patients with a mean age of 8.2 ± 2.7 years were analyzed. The average duration of epilepsy was 6 ± 2.8 years. The mean IQ was 72.4 ± 18.2 and mean CBCL score was 37.3 ± 11.8. There was negative correlation between IQ and CBCL ( r = -0.55, p < 0.001). The duration of epilepsy also showed negative correlation with IQ ( r = -4.75, p < 0.001). FDG PET scan showed predominant thalamic hypometabolism in 12 of 14 patients (85.7%) on visual analysis with multiple other hypometabolic cortical and subcortical regions in the brain. The quantitative analysis showed significant difference in metabolism of basal ganglion when compared with control group. The total number of hypometabolic regions seen in the brain showed moderate positive correlation with CBCL score but no significant correlation with the IQ of cases. Conclusion This study demonstrates functional impairment of cerebral cortical, basal ganglia, and thalamic hypometabolism in a cohort of ESES patients with normal structural MRI brain study. There was a moderate correlation of extent and pattern of cerebral hypometabolism with the neuropsychological status of the child and duration of epilepsy.

Synaptic Density and Glucose Consumption in Patients with Lewy Body Diseases: An [11 C]UCB-J and [18 F]FDG PET Study.

Patients with Lewy body diseases exhibit variable degrees of cortical and subcortical hypometabolism. However, the underlying causes behind this progressive hypometabolism remain unresolved. Generalized synaptic degeneration may be one key contributor. The objective of this study was to investigate whether local cortical synaptic loss is proportionally linked to the magnitude of hypometabolism in Lewy body disease. Using in vivo positron emission tomography (PET) we investigated cerebral glucose metabolism and quantified the density of cerebral synapses, as measured with [18 F]fluorodeoxyglucose ([18 F]FDG) PET and [11 C]UCB-J, respectively. Volumes-of-interest were defined on magnetic resonance T1 scans and regional standard uptake value ratios-1 values were obtained for 14 pre-selected brain regions. Between-group comparisons were conducted at voxel-level. We observed regional differences in both synaptic density and cerebral glucose consumption in our cohorts of non-demented and demented patients with Parkinson's disease or dementia with Lewy bodies compared to healthy subjects. Additionally, voxel-wise comparisons showed a clear difference in cortical regions between demented patients and controls for both tracers. Importantly, our findings strongly suggested that the magnitude of reduced glucose uptake exceeded the magnitude of reduced cortical synaptic density. Here, we investigated the relationship between in vivo glucose uptake and the magnitude of synaptic density as measured using [18 F]FDG PET and [11 C]UCB-J PET in Lewy body patients. The magnitude of reduced [18 F]FDG uptake was greater than the corresponding decline in [11 C]UCB-J binding. Therefore, the progressive hypometabolism seen in Lewy body disorders cannot be fully explained by generalized synaptic degeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain Metabolic Alterations in Seropositive Autoimmune Encephalitis: An 18F-FDG PET Study

Autoimmune encephalitis (AE) diagnosis and follow-up remain challenging. Brain 18F-fluoro-deoxy-glucose positron emission tomography (FDG PET) has shown promising results in AE. Our aim was to investigate FDG PET alterations in AE, according to antibody subtype. We retrospectively included patients with available FDG PET and seropositive AE diagnosed in our center between 2015 and 2020. Brain PET Z-score maps (relative to age matched controls) were analyzed, considering metabolic changes significant if |Z-score| ≥ 2. Forty-six patients were included (49.4 yrs [18; 81]): 13 with GAD autoantibodies, 11 with anti-LGI1, 9 with NMDAR, 5 with CASPR2, and 8 with other antibodies. Brain PET was abnormal in 98% of patients versus 53% for MRI. The most frequent abnormalities were medial temporal lobe (MTL) and/or striatum hypermetabolism (52% and 43% respectively), cortical hypometabolism (78%), and cerebellum abnormalities (70%). LGI1 AE tended to have more frequent MTL hypermetabolism. NMDAR AE was prone to widespread cortical hypometabolism. Fewer abnormalities were observed in GAD AE. Striatum hypermetabolism was more frequent in patients treated for less than 1 month (p = 0.014), suggesting a relation to disease activity. FDG PET could serve as an imaging biomarker for early diagnosis and follow-up in AE.

Thalamic pathology in frontotemporal dementia: Predilection for specific nuclei, phenotype-specific signatures, clinical correlates, and practical relevance.

Frontotemporal dementia (FTD) phenotypes are classically associated with distinctive cortical atrophy patterns and regional hypometabolism. However, the spectrum of cognitive and behavioral manifestations in FTD arises from multisynaptic network dysfunction. The thalamus is a key hub of several corticobasal and corticocortical circuits. The main circuits relayed via the thalamic nuclei include the dorsolateral prefrontal circuit, the anterior cingulate circuit, and the orbitofrontal circuit. In this paper, we have reviewed evidence for thalamic pathology in FTD based on radiological and postmortem studies. Original research papers were systematically reviewed for preferential involvement of specific thalamic regions, for phenotype-associated thalamic disease burden patterns, characteristic longitudinal changes, and genotype-associated thalamic signatures. Moreover, evidence for presymptomatic thalamic pathology was also reviewed. Identified papers were systematically scrutinized for imaging methods, cohort sizes, clinical profiles, clinicoradiological associations, and main anatomical findings. The findings of individual research papers were amalgamated for consensus observations and their study designs further evaluated for stereotyped shortcomings. Based on the limitations of existing studies and conflicting reports in low-incidence FTD variants, we sought to outline future research directions and pressing research priorities. FTD is associated with focal thalamic degeneration. Phenotype-specific thalamic traits mirror established cortical vulnerability patterns. Thalamic nuclei mediating behavioral and language functions are preferentially involved. Given the compelling evidence for considerable thalamic disease burden early in the course of most FTD subtypes, we also reflect on the practical relevance, diagnostic role, prognostic significance, and monitoring potential of thalamic metrics in FTD. Cardinal manifestations of FTD phenotypes are likely to stem from thalamocortical circuitry dysfunction and are not exclusively driven by focal cortical changes.

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach. We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median=5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike-high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations. Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus. These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. 18 F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.

Mirror writing and cortical hypometabolism in Parkinson's disease.

Mirror writing (MW) is the production of individual letters, words, or word strings in the reverse direction. Parkinson's disease (PD) is a progressive neurodegenerative disorder, and high MW rates have been reported in patients with PD. Thus, the present study sought to identify the factors that cause MW in patients with PD. We examined the frequency of MW in patients with PD and investigated the area of the brain where such frequency inversely correlates with reduced regional cerebral metabolic rates of glucose (rCMRglc). We also examined whether this area satisfied the motor and visual monitoring hypotheses of MW that have been presented in previous studies. Thirty-six subjects with idiopathic PD and 23 healthy controls were included in the study. We asked the participants to write down words, numerals, and sentences from left to right using their dominant and non-dominant hands. Patients with PD underwent an 18F-fluorodeoxyglucose positron emission tomography scan to measure the rCMRglc. Neither the patients with PD nor the healthy subjects exhibited MW in the use of the right hand. In the use of the left hand, MW occurred in 15 of the 36 patients with PD, but in none of the healthy controls. The right intraparietal sulcus was identified as the area where rCMRglc was inversely correlated with the number of left-right reversed characters. Previous functional imaging studies have suggested that the right superior parietal cortex and intraparietal sulcus play an important role in recognizing left-right reversed letters. Therefore, dysfunction in the intraparietal sulcus may hinder the recognition of left-right reversed characters, resulting in MW. Consequently, our findings in patients with PD are consistent with the visual-monitoring hypothesis of MW.

Effect of Single Session of Anodal M1 Transcranial Direct Current Stimulation-TDCS-On Cortical Hemodynamic Activity: A Pilot Study in Fibromyalgia.

Transcranial direct current stimulation (TDCS) on the primary motor cortex (M1) has been reported to be effective in fibromyalgia (FM). Our previous works have shown hypometabolism of motor networks in FM using Functional Near Infrared Spectroscopy (fNIRS), which could contribute to pain symptoms. To investigate if a single Transcranial Direct Current Stimulation (TDCS) session can restore the reduced metabolism expected in FM patients, we compared metabolic activity in FM patients and controls during a finger-tapping task in basal condition, sham condition, and under anodal TDCS on M1. During the finger tapping task, a continuous wave 20 channel fNIRS system was placed across the bilateral central-frontal areas in 22 healthy controls and 54 FM patients. Subjects were randomly assigned to real TDCS or sham stimulation. The finger-tapping slowness did not change after real and sham stimulation. After real TDCS stimulation, FM patients showed an increased activation of cortical motor regions (t-statistic = -2.5246, p-value = 0.0125 for the stimulated hemisphere and t-statistic = -4.6638, p-value = 0.0001 for the non-stimulated hemisphere). The basal differences between FM and controls reverted after real TDCS, while this effect was not observed for sham stimulation. A single TDCS session of the cortical motor network seemed able to restore basic cortical hypometabolism in FM patients. Further studies could clarify the long-term effect of M1 stimulation on cortical metabolism, and its relevance in pain processing and clinical features.

Brain metabolic correlates of Locus Coeruleus degeneration in Alzheimer's disease: a multimodal neuroimaging study

Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LCCR) and LC-belonging voxels (LCVOX). Both LCCR and LCVOX were significantly lower in patients compared to HCs, and were directly associated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.001, kE > 100). These results suggest a possible association between LC degeneration and cortical hypometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.