Marco Essig

Metabolic diseases are mostly congenital inborn errors leading to functional defects in metabolic pathways, whereas toxic and metabolic diseases in adults are usually acquired. MRI is the cornerstone in the assessment of these patients. The final diagnosis is often established in combination with laboratory findings and/or genetic analysis. Imaging patterns are almost invariably bilateral and often symmetric or nearly symmetric. The basal ganglia and thalami are often involved in acquired metabolic and toxic diseases. This chapter focuses on the most common inborn errors of metabolism that can present or persist into adulthood, as well as on the most common acquired metabolic and toxic disorders, relevant to daily clinical practice.

2041 Background: Patients with glioblastoma are often treated with radiation and chemotherapy following surgery. Disease recurrence often occurs early in the disease course and during initial therapy, yet assessment of treatment response with MRI is highly variable in some situations. We sought to describe the clinical and imaging assessment and outcomes of an unselected cohort of patients with glioblastoma following the publication of the Response Assessment in Neuro-Oncology criteria. Methods: Patients diagnosed with glioblastoma in Manitoba, Canada, from 2012-2018 were identified from the Manitoba Cancer Registry. Chart review was performed to identify treatments given and decisions made by the treating team, and imaging analysis was performed to assess based on RANO and mRANO criteria. Determination of progression versus pseudoprogression according to these criteria was performed using clinical decision-making and review of follow-up imaging for confirmation. At time of the response assessment visit, patients were assessed by a primary oncologist (Radiation or Medical) and were also discussed at multidisciplinary Case Conference (comprised of Medical and Radiation Oncology, Neurosurgery, Neuropathology, and Neuroradiology). Treatment decisions were made with patient and primary oncologist, guided by input from the Case Conference. Tumour measurements were performed both in 2D using Product of Perpendicular Diameter analysis (PPD) and 3D volumetric measurements with/without necrotic region. Overall Survival (OS) and Progression Free Survival (PFS) were estimated to evaluate the effectiveness of response assessments and Kaplan-Meier method was used to compare the time to progression resulted from RANO, mRANO, and clinical impression. Results: A total of 285 patients were identified with a pathological diagnosis of glioblastoma. Of those, 199 (35% male, 65% female) were treated with concurrent temozolomide and radiation (75% 60Gy and 25% < 60Gy), and more than 90% went on to receive adjuvant temozolomide. Median Overall Survival of the 199 was 13.2 months. Of those treated with concurrent therapy, 122 (61%) had MRI studies with equivocal results within the first 6 months, with confirmatory MRI showing true progression in 73 (59.8%), pseudoprogression in 45 (36.9%), and 4 patients with undetermined outcome. Formal RANO and mRANO comparison is ongoing. Conclusions: Response assessment for patients with glioblastoma remains a frequent challenge despite the use of MRI and established response criteria, with more than half of patients having equivocal imaging changes and a high frequency of pseudoprogression.

The Funding section of this manuscript has been updated. In the originally published version, the Funding section read as follows: The Aging Imageomics Study was funded by the Government of Catalonia's Department of Health's Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (file number, SLT002/16/00250); Toshiba Medical Systems (now Canon Medical Systems) provided a dedicated 1.5 T MRI scanner and ancillary MRI equipment for this study. The Spanish Ministry of Science, Innovation, and Universities (RTI2018-099200-B-I00, co-financed by FEDER funds from the European Union (“A way to build Europe”)); and the Generalitat of Catalonia (2017SGR696) to R.P. IRBLleida is a CERCA Programme/Generalitat of Catalonia; The Catalan project Imagenoma de L'Envelliment (Aging Imageomics Study to A.E.); The Spanish Ministry of Economy and Competitiveness, Spain (grant agreement number PSI2016-75688-P, MINECO/AEI/FEDER-EU to G.D.); European Union's Horizon 2020 FET Flagship Human Brain Project (grant agreement number 785907, HBP SGA2); the Catalan Research Support,...

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50–64 years versus older group (n = 310); age range, 65–91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local–global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups (‘middle-age group’ (n=310); age range, 50-65 years vs. ‘older group’ (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

The above article was published with one author name being incorrect. The published paper states “H. von Tengg”, whereas it should be “H.

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0–3) or poor (modified NIHSS 4–8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8–17), and the median modified NIHSS score was 5 (interquartile range = 2–8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78–1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

OBJECTIVE: Laser Ablation After Stereotactic Radiosurgery (LAASR) is a multicenter prospective study of laser interstitial thermal (LITT) ablation in patients with radiographic progression after stereotactic radiosurgery for brain metastases.METHODS: Patients with a Karnofsky Performance Scale (KPS) score ≥ 60, an age > 18 years, and surgical eligibility were included in this study. The primary outcome was local progression-free survival (PFS) assessed using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Secondary outcomes were overall survival (OS), procedure safety, neurocognitive function, and quality of life.RESULTS: Forty-two patients—19 with biopsy-proven radiation necrosis, 20 with recurrent tumor, and 3 with no diagnosis—were enrolled. The median age was 60 years, 64% of the subjects were female, and the median baseline KPS score was 85. Mean lesion volume was 6.4 cm³ (range 0.4–38.6 cm³). There was no significant difference in length of stay between the recurrent tumor and radiation necrosis patients (median 2.3 vs 1.7 days, respectively). Progression-free survival and OS rates were 74% (20/27) and 72%, respectively, at 26 weeks. Thirty percent of subjects were able to stop or reduce steroid usage by 12 weeks after surgery. Median KPS score, quality of life, and neurocognitive results did not change significantly for either group over the duration of survival. Adverse events were also similar for the two groups, with no significant difference in the overall event rate. There was a 12-week PFS and OS advantage for the radiation necrosis patients compared with the recurrent tumor or tumor progression patients.CONCLUSIONS: In this study, in which enrolled patients had few alternative options for salvage treatment, LITT ablation stabilized the KPS score, preserved quality of life and cognition, had a steroid-sparing effect, and was performed safely in the majority of cases.Clinical trial registration no.: NCT01651078 (clinicaltrials.gov)