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ALS is a neurodegenerative disease characterized by loss of motor neurons, resulting in progressive weakness and wasting of muscles. The average survival time is 2–5 years, mostly due to respiratory failure. Since current therapies can prolong survival time by only a few months, multidisciplinary care remains the cornerstone of the management of ALS. At the ALS Expert Centre of University Hospitals Leuven, a large proportion of Belgian ALS patients are seen for diagnosis and a significant number is also in follow-up with the multidisciplinary team. In this retrospective study, we compared the outcome of incident patients who were in follow-up at our site with patients who were not in follow-up. We included 659 patients of which 557 (84.5%) received specialized care at the ALS Expert Centre. After adjusting for clinically relevant prognostic parameters, multidisciplinary follow-up significantly prolonged survival (p = 0.004; HR = 0.683; CI 95% [0.528 − 0.884]). This increase in survival is mainly driven by patients with spinal onset (p = 0.035; HR = 0.746; CI 95% [0.568 − 0.980]), since no significant increased survival time was observed in patients with bulbar onset (p = 0.28; HR = 0.778; CI 95% [0.495 − 1.223]). These data confirm that multidisciplinary follow-up contributes to a better outcome of patients, emphasizing the importance of multidisciplinary specialized care in ALS. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder resulting in upper and lower motor neuron loss. ALS often has a focal onset of weakness, which subsequently spreads to other body regions. Survival is limited to two to five years after disease onset, often due to respiratory failure. Cognitive impairment is present in approximately 30% to 50% of patients and in 10%–15% of patients, the clinical criteria of frontotemporal dementia (FTD) are met. In this retrospective single-center ALS cohort study, we examined the occurrence of cognitive and behavioral impairment in relation to motor impairment at disease presentation and studied its impact on survival. The degree of lower motor neuron involvement was associated with a worse survival, but there was no effect for upper motor neuron involvement. Patients who were cognitively normal had a significantly better survival compared to patients with cognitive or behavioral impairment and to patients with comorbid FTD. There was no significant difference regarding survival between patients with FTD and patients with cognitive or behavioral impairment. The extent of motor and extramotor involvement in patients with ALS at disease presentation holds complementary prognostic information. [ABSTRACT FROM AUTHOR]

Objective: 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) single-center studies using support vector machine (SVM) approach to differentiate amyotrophic lateral sclerosis (ALS) from controls have shown high overall accuracy on an individual patient basis using local a priori defined classifiers. The aim of the study was to validate the SVM accuracy on a multicentric level. Methods: A previously defined Belgian (BE) group of 175 ALS patients (61.9 ± 12.2 years, 120M/55F) and 20 screened healthy controls (62.4 ± 6.4 years, 12M/8F) was used to classify another large dataset from Italy (IT), consisting of 195 patients (63.2 ± 11.6 years, 117M/78F) and 40 controls (62 ± 14.4 years; 29M/11F) free of any neurological and psychiatric disorder who underwent whole-body 18F-FDG PET-CT for lung cancer without any evidence of paraneoplastic symptoms. 18F-FDG within-center group comparisons based on statistical parametric mapping (SPM) were performed and SVM classifiers based on the local training sets were applied to differentiate ALS from controls from the other centers. Results: SPM group analysis showed only minor differences between both ALS groups, indicating pattern consistency. SVM using BE data set as training, classified 183/193 ALS-IT correctly (accuracy of 94.8%). However, 35/40 CON-IT were misclassified as ALS (accuracy 12.5%). Furthermore, using IT data as training, ALS-BE could not be distinguished from CON-BE. Within-center SPM group analysis confirmed prefrontal hypometabolism in CON-IT versus CON-BE, indicating subclinical brain changes in patients undergoing oncological scanning. Conclusion: This multicenter study confirms that the 18F-FDG ALS pattern is stable across centers. Furthermore, it highlights the importance of carefully selected controls, as subclinical frontal changes might be present in patients in an oncological setting. [ABSTRACT FROM AUTHOR]

Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare 18 F-DPA714, a second-generation translocator protein tracer, with 11 C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with 18 F-DPA714 and 11 C-JNJ717 was performed on human ALS brain sections in comparison to immunofluorescence with Iba1 and GFAP. For the in vivo portion, 3 male patients with early-stage ALS (59.3 ± 7.2 y old) and 6 healthy volunteers (48.2 ± 16.5 y old, 2 men and 4 women) underwent dynamic PET/MR scanning with 18 F-DPA714 and 11 C-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in 11 C-JNJ717 binding but did show increased 18 F-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in 18 F-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, 18 F-DPA714 showed increased signal whereas 11 C-JNJ717 was not elevated., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The Edinburgh cognitive and behavioral ALS screen (ECAS) was developed specifically to detect cognitive and behavioral changes in patients with amyotrophic lateral sclerosis (ALS). Differences with regard to normative data of different (language) versions of neuropsychological tests such as the ECAS exist., Objective: To derive norms for the Dutch version of the ECAS., Methods: Normative data were derived from a large sample of 690 control subjects and cognitive profiles were compared between a matched sample of 428 patients with ALS and 428 control subjects., Results: Age, level of education, and sex were significantly associated with performance on the ECAS in the normative sample. ECAS data were not normally distributed and therefore normative data were expressed as percentile ranks. The comparison of ECAS scores between patients and control subjects demonstrated that patients obtained significantly lower scores for language, executive function, verbal fluency, and memory, which is in line with the established cognitive profile of ALS., Conclusion: For an accurate interpretation of ECAS results, it is important to derive normative data in large samples with nonparametric methods. The present normative data provide healthcare professionals with an accurate estimate of how common or uncommon patients' ECAS scores are and provide a useful supplement to existing cut-off scores.

Objective: 18 F-Fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) single-center studies using support vector machine (SVM) approach to differentiate amyotrophic lateral sclerosis (ALS) from controls have shown high overall accuracy on an individual patient basis using local a priori defined classifiers. The aim of the study was to validate the SVM accuracy on a multicentric level., Methods: A previously defined Belgian (BE) group of 175 ALS patients (61.9 ± 12.2 years, 120M/55F) and 20 screened healthy controls (62.4 ± 6.4 years, 12M/8F) was used to classify another large dataset from Italy (IT), consisting of 195 patients (63.2 ± 11.6 years, 117M/78F) and 40 controls (62 ± 14.4 years; 29M/11F) free of any neurological and psychiatric disorder who underwent whole-body 18 F-FDG PET-CT for lung cancer without any evidence of paraneoplastic symptoms. 18 F-FDG within-center group comparisons based on statistical parametric mapping (SPM) were performed and SVM classifiers based on the local training sets were applied to differentiate ALS from controls from the other centers., Results: SPM group analysis showed only minor differences between both ALS groups, indicating pattern consistency. SVM using BE data set as training, classified 183/193 ALS-IT correctly (accuracy of 94.8%). However, 35/40 CON-IT were misclassified as ALS (accuracy 12.5%). Furthermore, using IT data as training, ALS-BE could not be distinguished from CON-BE. Within-center SPM group analysis confirmed prefrontal hypometabolism in CON-IT versus CON-BE, indicating subclinical brain changes in patients undergoing oncological scanning., Conclusion: This multicenter study confirms that the 18 F-FDG ALS pattern is stable across centers. Furthermore, it highlights the importance of carefully selected controls, as subclinical frontal changes might be present in patients in an oncological setting.