Dataset Information

Acetyl-DL-leucine in cerebellar ataxia ([¹⁸F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

ABSTRACT:

Objective

The aim of the study was to deepen our insights into central compensatory processes of brain networks in patients with cerebellar ataxia (CA) before and with treatment with acetyl-DL-leucine (AL) by means of resting-state [¹⁸F]-FDG-PET brain imaging.

Methods

Retrospective analyses of [¹⁸F]-FDG-PET data in 22 patients with CA (with vestibular and ocular motor disturbances) of different etiologies who were scanned before (PET A) and on AL treatment (PET B). Group subtraction analyses, e.g., for responders and non-responders, comparisons with healthy controls and correlation analyses of regional cerebral glucose metabolism (rCGM) with symptom duration, ataxia (SARA) and quality of life (QoL) scores were calculated.

Results

Prior to treatment rCGM was consistently downregulated at the cerebellar level and increased in multisensory cortical areas, e.g., somatosensory, primary and secondary visual (including V5, precuneus), secondary vestibular (temporal gyrus, anterior insula), and premotor/supplementary motor areas. With AL (PET B vs. A) cerebellar hypometabolism was deepened and sensorimotor hypermetabolism increased only in responders with clinical benefit, but not for the non-responders and the whole CA group. A positive correlation of ataxia improvement with rCGM was found in visual and vestibular cortices, a negative correlation in cerebellar and brainstem areas. QoL showed a positive correlation with rCGM in the cerebellum and symptom duration in premotor and somatosensory areas.

Conclusions

Central compensatory processes in CA mainly involve multisensory visual, vestibular, and somatosensory networks as well as premotor/primary motor areas at the cortical level. The enhanced divergence of cortical sensorimotor up- and cerebellar downregulation with AL in responders could reflect amplification of inhibitory cerebellar mechanisms.

SUBMITTER: Becker-Bense S

PROVIDER: S-EPMC9813104 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Acetyl-DL-leucine in cerebellar ataxia ([<sup>18</sup>F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

Becker-Bense Sandra S Kaiser Lena L Becker Regina R Feil Katharina K Muth Carolin C Albert Nathalie L NL Unterrainer Marcus M Bartenstein Peter P Strupp Michael M Dieterich Marianne M

Journal of neurology 20220725 1

<h4>Objective</h4>The aim of the study was to deepen our insights into central compensatory processes of brain networks in patients with cerebellar ataxia (CA) before and with treatment with acetyl-DL-leucine (AL) by means of resting-state [<sup>18</sup>F]-FDG-PET brain imaging.<h4>Methods</h4>Retrospective analyses of [<sup>18</sup>F]-FDG-PET data in 22 patients with CA (with vestibular and ocular motor disturbances) of different etiologies who were scanned before (PET A) and on AL treatment (P ...[more]

PMID: 35876876

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Project description:ImportanceCerebellar ataxia is a neurodegenerative disease impairing motor function characterized by ataxia of stance, gait, speech, and fine motor disturbances.ObjectiveTo investigate the efficacy, safety, and tolerability of the modified essential amino acid acetyl-DL-leucine in treating patients who have cerebellar ataxia.Design, setting, and participantsThe Acetyl-DL-leucine on Cerebellar Ataxia (ALCAT) trial was an investigator-initiated, multicenter, double-blind, randomized, placebo-controlled, clinical crossover trial. The study was conducted at 7 university hospitals in Germany and Austria between January 25, 2016, and February 17, 2017. Patients were aged at least 18 years and diagnosed with cerebellar ataxia of hereditary (suspected or genetically confirmed) or nonhereditary or unknown type presenting with a total score of at least 3 points on the Scale for the Assessment and Rating of Ataxia (SARA). Statistical analysis was performed from April 2018 to June 2018 and January 2020 to March 2020.InterventionsPatients were randomly assigned (1:1) to receive acetyl-DL-leucine orally (5 g per day after 2 weeks up-titration) followed by a matched placebo, each for 6 weeks, separated by a 4-week washout, or vice versa. The randomization was done via a web-based, permuted block-wise randomization list (block size, 2) that was stratified by disease subtype (hereditary vs nonhereditary or unknown) and site.Main outcomes and measuresPrimary efficacy outcome was the absolute change of SARA total score from (period-dependent) baseline to week 6.ResultsAmong 108 patients who were randomly assigned to sequence groups (54 patients each), 55 (50.9%) were female; the mean (SD) age was 54.8 (14.4) years; and the mean (SD) SARA total score was 13.33 (5.57) points. The full analysis set included 105 patients (80 patients with hereditary, 25 with nonhereditary or unknown cerebellar ataxia). There was no evidence of a difference in the mean absolute change from baseline to week 6 in SARA total scores between both treatments (mean treatment difference: 0.23 points [95% CI, -0.40 to 0.85 points]).Conclusions and relevanceIn this large multicenter, double-blind, randomized, placebo-controlled clinical crossover trial, acetyl-DL-leucine in the investigated dosage and treatment duration was not superior to placebo for the symptomatic treatment of certain types of ataxia. The drug was well tolerated; and ALCAT yielded valuable information about the duration of treatment periods and the role of placebo response in cerebellar ataxia. These findings suggest that further symptom-oriented trials are needed for evaluating the long-term effects of acetyl-DL-leucine for well-defined subgroups of cerebellar ataxia.Trial registrationEudraCT 2015-000460-34.

Project description:Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Project description:PurposeA general glucose metabolism pattern is observed in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis; however, it is unclear whether further subregional metabolic differences exist. Therefore, the present study aimed to conduct an in-depth exploration of the features of glucose metabolism within specific brain areas using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET).Materials and methodsThis retrospective study enrolled thirteen patients confirmed with LGI1 antibody encephalitis who were admitted to Beijing Tiantan Hospital from June 2021 to September 2022. All patients underwent 18F-FDG PET before initiating clinical treatment. Changes in glucose metabolism in specific brain areas were analyzed using Cortex ID software. The laterality of 18F-FDG uptake was assessed, and differences in specific brain areas were compared using paired t-tests.ResultsSignificant metabolic changes in at least one brain region in 11 out of 13 patients (84.6%) were revealed by semi-quantitative analysis (z-score > 2). A bilateral decrease in the 18F-FDG metabolic pattern was revealed in almost all brain regions of interest; in contrast, a hypermetabolic pattern was observed in the medial temporal region, with mean z-scores of 1.75 ± 3.27 and 2.36 ± 5.90 on the left and right sides, respectively (p = 0.497). In the prefrontal and temporal lobes, 18F-FDG metabolism was significantly lower in the lateral region than in the medial region on both sides. For the cingulate cortex, significant hypometabolism was also observed in the posterior part compared to the anterior counterpart on both the left (z-score: -1.20 ± 1.93 vs. -0.42 ± 1.18, respectively; p = 0.047) and right (z-score: -1.56 ± 1.96 vs. -0.33 ± 1.63, respectively; p = 0.001) sides. However, a significant difference in regional metabolism was observed only on the left side (p = 0.041).ConclusionAn asymmetric 18F-FDG metabolic pattern exists in patients with anti-LGI1 encephalitis. Meanwhile, varied regional metabolic differences were revealed bilaterally in specific cerebral areas, which could be associated with the clinical manifestations.

Dataset Information

Acetyl-DL-leucine in cerebellar ataxia ([¹⁸F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

Objective

Methods

Results

Conclusions

Publications

Acetyl-DL-leucine in cerebellar ataxia ([<sup>18</sup>F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Acetyl-DL-leucine in cerebellar ataxia ([18F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

Objective

Methods

Results

Conclusions

Publications

Acetyl-DL-leucine in cerebellar ataxia ([<sup>18</sup>F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Acetyl-DL-leucine in cerebellar ataxia ([¹⁸F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?