Positron emission tomography neuroimaging in neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Neurodegenerative diseases are a growing problem of ageing societies. Their insidious onset, and the lack of reliable biomarkers, result in significant diagnosis delays. This article summarises the results of studies on the use of positron emission tomography (PET) in the diagnosis of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. It focuses on clinical-pathogenetic aspects of individual diseases, as well as disease-specific patterns relevant in differential diagnosis and in assessing the risk of disease development and prognosis

Gastrostomy and mechanical ventilation in amyotrophic lateral sclerosis: how best to support the decision-making process?

The unfavourable outcome of amyotrophic lateral sclerosis (ALS) confronts patients with challenging decisions regarding life-sustaining measures. The decision-making process is usually triggered by medical consultations and patient-dependent factors. This may largely depend on the physician’s depth of knowledge and professional experience. This paper presents an overview of the life-sustaining methods used in ALS and their effects on disease progression, survival and quality of life of patients and their caregivers. It is intended to aid physicians in their discussions with patients. We interrogate all the positive and negative facets of life-sustaining measures that may allow for optimisation of the decision-making process and care provision

Role of DTI-MRI parameters in diagnosis of ALS: useful biomarkers for daily practice? Tertiary centre experience and literature review

Introduction. Despite the rapid development of neuroimaging techniques, the diagnosis of amyotrophic lateral sclerosis (ALS) remains a significant challenge. Magnetic resonance imaging (MRI) is important for ruling out ALS mimickers, while Diffusion Tensor Imaging (DTI) is a useful tool for the identification of cortical tract damage. The aim of this study was to identify the optimal set of DTI parameters to support the diagnosis of ALS that could be applied to everyday MRI and be used as a disease biomarker in daily practice. Material and methods. Forty-seven ALS patients and 55 age- and gender-matched healthy individuals underwent MRI using a 1.5-Tesla scanner including a DTI sequence with 30 spatial directions and a b-value 0/1,000 s/mm2. Two independent researchers measured the DTI parameters: fractional anisotropy (FA), TRACE and apparent diffusion coefficient (ADC) using freehand regions of interest (ROIs) placed along both corticospinal tracts (CSTs), starting at the level of the internal capsule and ending at the medulla. Results. Statistical significance was only achieved for fractional anisotropy (FA) (ALS vs controls, p < 0.001). The highest sensitivity was found in the brainstem (cerebral peduncles, pons and pyramids) where it ranged from 72.3% to 80.9%, whereas the highest specificity was observed at the level of the internal capsule (94.6%). The combined highest sensitivity and specificity was obtained in the pons (72.3% and 72.7%, respectively). Classifier based positive predictive values for Youden index cut-off scores varied between 60.7% and 69.4%. Conclusions. Fractional anisotropy (FA) measured at the level of the brainstem was shown to be the single most relevant parameter in differentiating patients with ALS from healthy subjects. This has the potential to become an ALS-specific biomarker for patient identification in daily practice

Emotional lability at disease onset is an independent prognostic factor of faster disease progression in Amyotrophic Lateral Sclerosis

Copyright: © 2019 Barc K et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Amyotrophic lateral sclerosis (ALS) is a fast progressing neurodegenerative disease leading to quadriplegia, anarthria and respiratory insufficiency. A large variety of phenotypes and disability progression requires individually tailored management. Identification of predictors of poor prognosis may not only improve management, but also allow for more precise patients' stratification for clinical trials or research studies. The aim of the study was to investigate the influence of emotional lability present at disease onset on ALS progression by exploring its direct impact on the decay of the ALS Functional Rating Scale-Revised (ALSFRS-R). The study was performed in a group of 1145 patients from Germany, Poland, Portugal and Turkey between 2014 and 2018. The analysis showed that the presence of emotional lability at ALS onset was linked to a faster decline of ALSFRS-R (0.70 vs 0.50, p<0.0001), in case of either bulbar (0.80 vs 0.65, p<0.05) or limb disease onset (0.59 vs 0.46, p <0.01). It was most prominent in the bulbar subscore of ALSFRS-R. A multiple regression analysis showed a direct influence of emotional lability at ALS onset on disease progression, regardless of age, gender, site of onset, weight loss, cognitive impairment and diagnosis delay (β=0.071; p=0.019). It can therefore be concluded that the presence of emotional lability at the disease onset is an independent factor of faster disease progression in ALS.This study was supported by OnWebDuals project (JNPD 01ED1511B; DZP/2/JPND-III/2015). This is an EU Joint Programme - Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organization under the aegis of JPND - www.jpnd.eu: Germany, Bundes-ministerium für Bildung und Forschung (BMBF); Poland, Narodowe Centrum Badań i Rozwoju (NCBiR); Portugal, Fundação a Ciência e a Tecnologia (FCT); Sweden, Vetenskapsrådet (VR).info:eu-repo/semantics/publishedVersio

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

Changes in kinesin expression in the CNS of mice with dynein heavy chain 1 mutation

Dysfunction of fast axonal transport, vital for motor neurons, may lead to neurodegeneration. Anterograde transport is mediated by N-kinesins (KIFs), while retrograde transport by dynein 1 and, to a minor extent, by C-kinesins. In our earlier studies we observed changes in expression of N- and C-kinesins (KIF5A, 5C, C2) in G93ASOD1-linked mouse model of motor neuron degeneration. In the present work we analyze the profile of expression of the same kinesins in mice with a dynein 1 heavy chain mutation (Dync1h1, called Cra1), presenting similar clinical symptoms, and in Cra1/SOD1 mice with milder disease progression than SOD1 transgenics. We found significantly higher levels of mRNA for KIF5A and KIF5C but not the KIFC2 in the frontal cortex of symptomatic Cra1/+ mice (aged 365 days) compared to the wild-type controls. No changes in kinesin expression were found in the spinal cord of any age group and only mild changes in the hippocampus. The expression of kinesins in the cerebellum of the presymptomatic and symptomatic mice (aged 140 and 365 days, respectively) was much lower than in age-matched controls. In Cra1/SOD1 mice the changes in KIFs expression were similar or more severe than in the Cra1/+ groups, and they also appeared in the spinal cord. Thus, in mice with the Dync1h1 mutation, which impairs dynein 1-dependent retrograde transport, expression of kinesin mRNA is affected in various structures of the CNS and the changes are similar or milder than in mice with double Dync1h1/hSOD1G93A mutations

Differences in glutathione S-transferase pi expression in transgenic mice with symptoms of neurodegeneration

Glutathione S-transferase pi (GST pi) is an enzyme involved in cell protection against toxic electrophiles and products of oxidative stress. GST pi expression was studied in transgenic mice hybrids (B6-C3H) with symptoms of neurodegeneration harboring SOD1G93A (SOD1/+), Dync1h1 (Cra1/+) and double (Cra1/SOD1) mutations, at presymptomatic and symptomatic stages (age 70, 140, 365 days) using RT-PCR and Western blotting. The main changes in GST pi expression were observed in mice with the SODG93A mutation. In SOD1/+ and Cra1/SOD1 transgenics, with the exception of cerebellum, the changes in GST pi-mRNA accompanied those in GST pi protein. In brain cortex of both groups the expression was unchanged at the presymptomatic (age 70 days) but was lower at the symptomatic stage (age 140 days) and at both stages in hippocampus and spinal cord of SOD1/+ but not of Cra1/SOD1 mice compared to age-matched wild-type controls. In cerebellum of the presymptomatic and the symptomatic SOD1/+ mice and presymptomatic Cra1/SOD1 mice, the GST pi-mRNA was drastically elevated but the protein level remained unchanged. In Cra1/+ transgenics there were no changes in GST pi expression in any CNS region both on the mRNA and on the protein level. It can be concluded that the SOD1G93A but not the Dync1h1 mutation significantly decreases detoxification efficiency of GST pi in CNS, however the Dync1h1 mutation reduces the effects caused by the SOD1G93A mutation. Despite similarities in neurological symptoms, the differences in GST pi expression between SOD1/+ and Cra1/+ transgenics indicate a distinct pathogenic entity of these two conditions