Posterior reversible encephalopathy syndrome associated with antibiotic therapy: a case report and systematic review.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition associated with different etiologies, including antibiotic therapy. To date, most data regarding antibiotic-related PRES are limited to case reports and small case series. Here, we report a novel case description and provide a systematic review of the clinico-radiological characteristics and prognosis of available cases of PRES associated with antibiotic therapy. We performed a systematic literature search in PubMed and Scopus from inception to 10 January 2024, following PRISMA guidelines and a predefined protocol. The database search yielded 12 subjects (including our case). We described the case of a 55-year-old female patient with PRES occurring one day after administration of metronidazole and showing elevated serum neurofilament light chain protein levels and favorable outcome. In our systematic review, antibiotic-associated PRES was more frequent in female patients (83.3%). Metronidazole and fluoroquinolones were the most reported antibiotics (33.3% each). Clinical and radiological features were comparable to those of PRES due to other causes. Regarding the prognosis, about one third of the cases were admitted to the intensive care unit, but almost all subjects (90.0%) had a complete or almost complete clinical and radiological recovery after prompt cessation of the causative drug. Antibiotic-associated PRES appears to share most of the characteristics of classic PRES. Given the overall good prognosis of the disease, it is important to promptly diagnose antibiotic-associated PRES and discontinue the causative drug.

Longitudinal changes in surface based brain morphometry measures in amnestic mild cognitive impairment and Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is associated with marked brain atrophy. While commonly used structural MRI imaging methods do not account for the complexity of human brain morphology, little is known about the longitudinal changes of cortical geometry and their relationship with cognitive decline in subjects with AD. METHODS: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to perform two-sample t-tests to investigate longitudinal changes of cortical thickness (CTh) and three surface-based morphometry measures: fractal dimension (i.e. cortical complexity; FD), gyrification index (GI), and sulcal depth (SD) in subjects with AD, amnestic mild cognitive impairment (aMCI) in comparison to cognitively unimpaired controls (CU) in baseline and 2-year follow-up sMRI scans. In addition, correlations of the morphological measures with two-year cognitive decline as assessed by the modified AD Assessment Scale-Cognitive Subscale (ADAS-Cog 11) were calculated via regression analyses. RESULTS: Compared to CU, both AD and aMCI showed marked decreases in CTh. In contrast, analyses of FD and GI yielded a more nuanced decline of the respective measures with some areas showing increases in FD and GI. Overall changes in FD and GI were more pronounced in AD as compared to aMCI. Analyses of SD yielded widespread decreases. Interestingly, cognitive decline corresponded well with CTh declines in aMCI but not AD, whereas changes in FD corresponded with AD only but not aMCI, whereas GI and SD were associated with cognitive decline in aMCI and AD. CONCLUSION: Patterns of longitudinal changes in FD, GI and SD were only partially overlapping with CTh reductions. In AD, surface-based morphometry measures for brain-surface complexity showed better correspondence than CTh with cognitive decline over a two-year period of time. Being drawn from measures reflecting changes in more intricate aspects of human brain morphology, these data provide new insight into the complexity of AD-related brain atrophy and its relationship with cognitive decline.

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

Introduction: Several studies have suggested that greater adiposity in older adults is associated with a lower risk of Alzheimer's disease (AD) related cognitive decline, some investigators have postulated that this association may be due to the protective effects of the adipose tissue-derived hormone leptin. In this study we sought to demonstrate that higher body mass indices (BMIs) are associated with greater baseline FDG PET measurements of the regional cerebral metabolic rate for glucose (rCMRgl), a marker of local neuronal activity, slower rCMRgl declines in research participants with amnestic mild cognitive impairment (aMCI). We then sought to clarify the extent to which those relationships are attributable to cerebrospinal fluid (CSF) or plasma leptin concentrations. Materials and methods: We used baseline PET images from 716 73 ± 8 years-old aMCI participants from the AD Neuroimaging Initiative (ADNI) of whom 453 had follow up images (≥6 months; mean follow up time 3.3 years). For the leptin analyses, we used baseline CSF samples from 81 of the participants and plasma samples from 212 of the participants. Results: As predicted, higher baseline BMI was associated with greater baseline CMRgl measurements and slower declines within brain regions preferentially affected by AD. In contrast and independently of BMI, CSF, and plasma leptin concentrations were mainly related to less baseline CMRgl within mesocorticolimbic brain regions implicated in energy homeostasis. Discussion: While higher BMIs are associated with greater baseline CMRgl and slower declines in persons with aMCI, these associations appear not to be primarily attributable to leptin concentrations.

PET/MRI Delivers Multimodal Brain Signature in Alzheimer's Disease with De Novo PSEN1 Mutation.

BACKGROUND: Little is known so far about the brain phenotype and the spatial interplay of different Alzheimer's disease (AD) biomarkers with structural and functional brain connectivity in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to fill this gap. MATERIAL AND METHODS: We presented a 31-year-old male patient without a family history of dementia with progressive worsening of memory and motor function. Two separate sessions of 3T PET/MRI acquisitions were arranged with the ß-amyloid tracer [18F]Florbetaben and the secondgeneration tau tracer [18F]PI-2620. Simultaneously acquired MRI consisted of high-resolution 3D T1, diffusion-tensor imaging (DTI), and resting-state fMRI. PET/MRI data were compared with ten age-matched healthy controls. RESULTS: Widespread ß-amyloid depositions were found in cortical regions, and striatum (Thal stage III) along with tau pathology restricted to the mesial-temporal structures (Braak stage III/IV). Volumetric/shape analysis of subcortical structures revealed atrophy of the hippocampal-amygdala complex. In addition, cortical thinning was detected in the right middle temporal pole. Alterations of multiple DTI indices were noted in the major white matter fiber bundles, together with disruption of default mode and sensory-motor network functional connectivity. Molecular genetic analysis by next-generation sequencing revealed a heterozygote missense pathogenic variant of the PSEN1 (Met233Val). CONCLUSION: Multimodal PET/MR imaging is able to deliver, in a one-stop-shop approach, an array of molecular, structural and functional brain information in AD due to de novo pathogenic variant, which can be studied for spatial interplay and might provide a rationale for initiating anti- amyloid/tau therapeutic approaches.

Hippocampal gray matter volume in the long-term course after transient global amnesia.

OBJECTIVE: In this retrospective, cross-sectional study we aimed to examine long-term memory deficits and gray matter volumes (GMV) in the hippocampus after transient global amnesia (TGA). METHODS: 20 patients with a history of TGA (TGA+, mean 6.5 years after TGA) and 20 age-matched healthy controls (TGA-) underwent neurocognitive assessment (i.e. Mini-Mental State Examination (MMSE), visuospatial, verbal and episodic autobiographical memory and visuospatial learning/navigation ["human water maze"]) in combination with structural cerebral MRI. Voxel-based morphometry (VBM) was used to detect GMV in the hippocampus in TGA+ versus TGA-. RESULTS: Besides slight differences in MMSE and visuo-spatial learning/navigation measured with a human water maze in TGA+ vs. TGA-, no other tests of visuo-spatial, verbal and autobiographical long-term memory differed between groups. VBM analyses yielded a statistically significant difference in bilateral hippocampal GMV with TGA+ compared to TGA- showing greater GMV in a region corresponding to bilateral CA1. However, none of the hippocampus-dependent cognitive measures correlated with hippocampal GMV. CONCLUSION: In the long-term course after TGA, only subtle neurocognitive deficits without microstructural damage of the hippocampus could be detected. Greater GMV in bilateral hippocampus in TGA+ vs. TGA- may indicate that TGA triggers hippocampal GMV increase rather than atrophy.

Brain structural differences in monozygotic twins discordant for body mass index.

BACKGROUND: Substantial efforts have been made to investigate the neurobiological underpinnings of human obesity with a number of studies indicating a profound influence of increased body weight on brain structure. Although body weight is known to be highly heritable, uncertainty remains regarding the respective contribution of genetic and environmental influences. METHODS: In this study we used structural magnetic resonance imaging (MRI) data from the Human Connectome Project (HCP). Voxel-based morphometry (VBM) was applied to study BMI-associated differences in gray matter volume (GMV) within monozygotic (MZ) twin pairs discordant for BMI (ΔBMI â€‹> â€‹2.5 â€‹kg*m-2, n = 68 pairs). In addition, we investigated the relationship of ΔBMI (entire range) with GMV differences within the entire sample of MZ twin pairs (n = 153 pairs). RESULTS: Analyses of BMI discordant twin pairs yielded less GMV in heavier twin siblings (p < 0.05 FWETFCE; paired t-Test) within the occipital and cerebellar cortex, the prefrontal cortex and the bilateral striatum including the nucleus accumbens. A highly converging pattern was found in regression analyses across the entire sample of MZ twin pairs, with ΔBMI being associated with less GMV in heavier MZ twins. CONCLUSION: While MZ twins share the same genetic background, our findings indicate that non-genetic influences and the mere presence of a higher BMI constitute relevant factors in the context of body weight related structural brain alterations.

When less is more: Structural correlates of core executive functions in young adults - A VBM and cortical thickness study.

BACKGROUND: The term executive functions (EF) describes a set of higher cognitive abilities/skills needed for goal-oriented and flexible behavior. In contrast to a multitude of functional neuroimaging studies of EF performance, only limited and partially inconclusive data is available for the structural-neuroanatomical underpinnings of EFs, particularly in healthy adults. METHODS: Here, we applied voxel-based morphometry (VBM) and additional analyses of cortical thickness (CTH; via surface-based morphometry) to a large sample of healthy young adults from the Human Connectome Project (N = 1110; Age 28.8 ±â€¯3.7 years) with structural MRI data and test data reflective of three core EFs [i.e. cognitive flexibility (CF), inhibitory control (IC) and working memory (WM)]. RESULTS: For CF and IC, VBM analyses yielded a distinct and largely overlapping pattern of exclusively negative associations (CF>IC), most prominently within the medial prefrontal cortex, the insular cortex, central/precentral regions, subcortical and mesotemporal structures. A similar, yet less pronounced pattern of negative associations was found in analyses of CTH. In contrast, both VBM and CTH analyses yielded no significant associations with WM performance. CONCLUSIONS: Brain regions we found negatively associated with measures of CF and IC have been repeatedly highlighted by functional imaging studies of EF performance. The here observed inverse relationship with brain structural parameters may be related to the young age of our study population and well established neurobiological mechanisms of cortical maturation (i.e. cortical thinning via synaptic pruning and cortical myelination).

Central Effects of Botulinum Neurotoxin-Evidence from Human Studies.

For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT's pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT's central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered "side-effects" but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions.

Left lateralized cerebral glucose metabolism declines in amyloid-ß positive persons with mild cognitive impairment.

Background: Previous publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism. Methods: Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-ß (Aß) positivity, 40 Aß negative (Aß-) cognitively unimpaired controls (CU; 76 ±â€¯5y), 76 Aß positive (Aß+) persons with MCI (76 ±â€¯7y) and 51 Aß + persons with probable AD dementia (75 ±â€¯7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aß + MCI and AD in comparison with Aß- CU were statistically quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1 (left)]. Results: Compared to Aß- CU, Aß + MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: -0.33) of rCMRgl declines was found in Aß + persons with probable AD dementia. Additional comparisons of Aß + groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD. Conclusions: These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.

Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial.

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity.Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity.Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m2): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables.Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals (P = 0.01), after long-term tDCS.Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362.

Neuromodulation targeted to the prefrontal cortex induces changes in energy intake and weight loss in obesity.

OBJECTIVE: Obesity is associated with decreased activity in the prefrontal cortex. Transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating. The energy intake (EI) and body weight in subjects who received cathodal versus sham (study 1) and subsequent anodal versus sham (study 2) tDCS aimed at the left dorsolateral prefrontal cortex (LDLPFC) were measured. METHODS: Nine (3m, 6f) healthy volunteers with obesity (94 ± 15 kg [M ± SD]; 42 ± 8 y) were admitted as inpatients for 9 days to participate in a double-blind, randomized, placebo-controlled crossover experiment. Study 1: following 5 days of a weight-maintaining diet, participants received cathodal or sham tDCS (2 mA, 40 min) on three consecutive mornings and then ate ad libitum from a computerized vending machine, which recorded EI. Weight was measured daily. Study 2: participants repeated the study, maintaining original assignment to active (this time anodal) and sham. RESULTS: Participants tended to consume fewer kilocalories per day (P = 0.07), significantly fewer kilocalories from soda (P = 0.02) and fat (P = 0.03), and had a greater % weight loss (P = 0.009) during anodal versus cathodal tDCS. CONCLUSIONS: The results indicated a role for the LDLPFC in obesity and food intake. This proof of concept study suggested, for the first time, the potential application of anodal tDCS to facilitate weight loss.

A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study.

Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs.

A post-mortem stereological study of striatal cell number in human obesity.

OBJECTIVE: Neuroimaging studies have revealed abnormalities in brain structure, including the striatum, in obese people. In this study, the cellular and parenchymal basis for these findings in post-mortem brain tissue was investigated. METHODS: Design-based (unbiased) stereology combined with histochemical and immunocytochemical staining was used to quantify total number of neurons and astrocytes in post-mortem striatal brain samples from nine obese (BMI 40.2 ± 6.1 kg/m(2) ) and eight lean (BMI 24.4 ± 1.0 kg/m(2) ) donors. Total numbers of Nissl-stained neurons and glial fibrillary acidic protein-immunopositive astrocytes were counted in 10 systematic-random sections starting from the frontal pole of the striatum. RESULTS: There were no differences in mean total numbers of neurons (obese: 7.60 E+06; SD 2.50 E+06; lean: 7.85 E+06; SD 8.26 E+05; P < 0.78) or astrocytes (obese: 7.42 E+06; SD 2.27 E+06; lean: 7.43 E+06; SD 2.50 E+06; P < 0.99). A higher variance was found for number of neurons (P < 0.007) but not astrocytes (P < 0.72) in the obese group. Neuron/glia ratios were similar in both groups (obese: 1.07, SD 0.39; lean: 1.15, SD 0.37; P < 0.70) with an overall striatal neuron/glia ratio of 1.11 (SD 0.37) across the entire study population (n = 17). CONCLUSIONS: No difference was found in the average numbers of neurons and astrocytes in the anterior striatum between lean and obese people. The morphological basis for structural brain changes in obesity requires further investigation.

Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation.

Obesity has been associated with alterations of both functional and structural aspects of the human central nervous system. In obese individuals both fat mass (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non-adipose tissues) are increased and it remains unknown whether these compartments have separate effects on human brain morphology. We used voxel-based morphometry to investigate the relationships between measures of body composition and regional gray matter volume (GMV) in 76 healthy adults with a wide range of adiposity (24 F/52 M; age 32.1 ± 8.8 years; percentage of body fat [PFAT%] 25.5 ± 10.9%; BMI 29.8 ± 8.9). Fat-free mass index (FFMI kg × m(-2)) showed negative associations in bilateral temporal regions, the bilateral medial and caudolateral OFC, and the left insula. Fat mass index (FMI kg × m(-2)) showed similar, but less extensive negative associations within temporal cortical regions and the left caudolateral orbitofrontal cortex (OFC). In addition, negative associations were seen for FMI with GMV of the cerebellum. Associations of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of adiposity. No associations were seen between measures of adiposity (i.e. FM and PFAT) and GMV when adjusted for FFM. The majority of regions that we find associated with FFM have been implicated in the regulation of eating behavior and show extensive projections to central autonomic and homeostatic core structures. These data indicate that not adipose tissue or relative adiposity itself, but obesity related increases in absolute tissue mass and particularly FFM may have a more predominant effect on the human brain. This might be explained by the high metabolic demand of FFM and related increases in total energy needs.

Postprandial plasma PYY concentrations are associated with increased regional gray matter volume and rCBF declines in caudate nuclei--a combined MRI and H2(15)O PET study.

The anorexigenic gastrointestinal hormone Peptide YY plays an important role in the communication between the gastrointestinal tract and the central nervous system. PYY has been shown to modulate brain activity in regions implicated in reward and food related behavior. Its effects on brain structure however, remain unknown. Voxel-based morphometry was used to investigate the relationship between fasting and postprandial plasma PYY concentrations and regional gray matter volume (GMV). For this analysis twenty adult, non diabetic Caucasians were included (18F/2M, age 31±9 y, percentage of body fat [PFAT] 32±8%) who had volumetric brain magnetic resonance images and underwent H(2)(15)O positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF), a marker of local neuronal activity, and measurements of plasma total PYY, prior to (fasting) and following a satiating liquid meal. Voxel-wise analysis revealed a regional positive association between postprandial PYY and gray matter volume bilaterally in the caudate nuclei. These associations remained significant (p<0.05) after small volume correction for multiple comparisons. Based on these findings we investigated whether postprandial PYY is associated with PET measured rCBF of the caudate nucleus. We found a significant negative association between average postprandial caudate rCBF and postprandial plasma PYY concentrations (r=-0.60, p<0.02, age, sex and PFAT adjusted). Average postprandial caudate rCBF was also negatively associated with rCBF in the right medial orbitofrontal cortex and the right hippocampal formation (p<0.05, corrected for multiple comparisons). Total PYY is positively associated with gray matter but negatively with postprandial activity in the caudate nuclei while caudate activity is negatively associated with rCBF in prefrontal and paralimbic regions implicated in reward behavior. Thus, PYY may act centrally to modulate eating behavior via striatal networks.