2011 Oct - Volonté C, Apolloni S, Carrì MT, D'Ambrosi N

CNR-Cell Biology and Neurobiology Institute, Via del Fosso di Fiorano 64, 00143 Rome, Italy. cinzia.volonte@inmm.cnr.it

Pharmacology & therapeutics

Amyotrophic lateral sclerosis (ALS) is one of the most common neuromuscular diseases. It is devastating and fatal, causing progressive paralysis of all voluntary muscles and eventually death, while sparing cognitive functions. A pathological hallmark of ALS is neuroinflammation mediated by non-neuronal cells in the nervous system, such as microglia and astrocytes that accelerate the disease progression. Scientists have neither found a unique key mechanism, nor an effective treatment against ALS, supposedly because it is a multi-factorial and multi-systemic disease. Extracellular purines and pyrimidines are widespread and powerful physiopathological molecules, signalling to most cell types and directing cell-to-cell communication networks. They are instrumental for instance for neurotransmission, muscle contraction and immune surveillance. Recent work has reported the crucial involvement of purinergic pathways in many neurodegenerative and neuroinflammatory diseases, comprising ALS.

2011 Oct - Volonté C, Apolloni S, Carrì MT, D'Ambrosi N

CNR-Cell Biology and Neurobiology Institute, Via del Fosso di Fiorano 64, 00143 Rome, Italy. cinzia.volonte@inmm.cnr.it

Pharmacology & therapeutics

Especially P2 receptors for ATP, P1 receptors for adenosine, and nucleotide transporters were found to be modulated in ALS cells and tissues, playing a potential role in the disease. Given the composite cellular cross-talk occurring during ALS and the established action of extracellular purines/pyrimidines as neuron-to-glia alarm signal in the nervous system, a mutual query in these two fields should now be whether, how and when purinergic would meet ALS. In this review, we will highlight the early cellular and molecular purinergic cross-talk that participates to ALS etiopathology, with the conviction that better understanding of purinergic dynamics might provide original research perspectives, stimulate alternative disease modelling, and the design and testing of more powerful targeted therapeutics against this relentlessly progressive disorder.

2011 Jun 14 - van Groenestijn AC, van de Port IG, Schröder CD, Post MW, Grupstra HF, Kruitwagen ET, van der Linde H, van Vliet RO, van de Weerd MG, van den Berg LH, Lindeman E

Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, The Netherlands.

BMC neurology

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder affecting motor neurons in the spinal cord, brainstem and motor cortex, leading to muscle weakness. Muscle weakness may result in the avoidance of physical activity, which exacerbates disuse weakness and cardiovascular deconditioning. The impact of the grave prognosis may result in depressive symptoms and hopelessness.Since there is no cure for ALS, optimal treatment is based on symptom management and preservation of quality of life (QoL), provided in a multidisciplinary setting. Two distinctly different therapeutic interventions may be effective to improve or preserve daily functioning and QoL at the highest achievable level: aerobic exercise therapy (AET) to maintain or enhance functional capacity and cognitive behavioural therapy (CBT) to improve coping style and cognitions in patients with ALS.

2011 Jun 7 - Weis J, Katona I, Müller-Newen G, Sommer C, Necula G, Hendrich C, Ludolph AC, Sperfeld AD

Institute of Neuropathology, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany. jweis@ukaachen.de

Neurology

OBJECTIVE: To investigate the involvement of the epidermal small sensory fibers in the neurodegenerative process in amyotrophic lateral sclerosis (ALS) . METHODS: In the present study, skin biopsies of 28 patients with ALS were obtained at an average of 34 months after disease onset by history. Protein gene product 9.5 (PGP9.5) immunohistochemistry findings were compared to 17 age-matched controls. The primary endpoint of the study was to evaluate the decrease in the density of small intraepidermal nerve fibers and to compare the prevalence of small-fiber neuropathy in patients with ALS and in controls. RESULTS: We found a significant reduction in epidermal nerve fiber density in the distal calf of patients with ALS (4.8 ± 3.7 fibers/mm vs 12.2 ± 4.6 in age-matched controls, p<0.0001). The extent of fiber loss was age-dependent. Also, the number of subjects with small-fiber neuropathy was significantly higher in the ALS group than in the controls (79% vs 12%).

2011 Jun - Hilton P, Robinson D

Royal Victoria Infirmary, Newcastle upon Tyne, UK. paul.hilton@ncl.ac.uk

Neurourology and urodynamics

This paper is a summary of the presentations made as Proposal 2-"Defining cure& quot; to the 2nd Annual meeting of the ICI-Research Society, in Bristol, 16th June 2010. It reviews definitions of 'cure' and 'outcome', and considers the impact that varying definition may have on prevalence studies and cure rates. The difference between subjective and objective outcomes is considered, and the significance that these different outcomes may have for different stakeholders (e.g. clinicians, patients, carers, industry etc.) is discussed. The development of patient reported outcome measures and patient defined goals is reviewed, and consideration given to the use of composite end-points. A series of proposals are made by authors and discussants as to how currently validated outcomes should be applied, and where our future research activity in this area might be directed.

2011 Apr 14 - Beukelman D, Fager S, Nordness A

Institute for Rehabilitation Science and Engineering Madonna Rehabilitation Hospital and University of Nebraska, 202 Barkley Memorial Center, P.O. Box 830732, Lincoln, NE 68583-0732, USA.

Neurology research international

Almost all people with amyotrophic lateral sclerosis (ALS) experience a motor speech disorder, such as dysarthria, as the disease progresses. At some point, 80 to 95% of people with ALS are unable to meet their daily communication needs using natural speech. Unfortunately, once intelligibility begins to decrease, speech performance often deteriorates so rapidly that there is little time to implement an appropriate augmentative and alternative communication (AAC) intervention; therefore, appropriate timing of referral for AAC assessment and intervention continues to be a most important clinical decision-making issue. AAC acceptance and use have increased considerably during the past decade. Many people use AAC until within a few weeks of their deaths.

2011 Apr 1 - Nassif M, Hetz C

Center for Molecular Studies of the Cell; Institute of Biomedical Sciences; Biomedical Neuroscience Institute; Faculty of Medicine; University of Chile; Santiago, Chile.

Autophagy

Recent evidence, however, indicates that the expression of several disease-related genes may actually impair autophagy activity at different levels, including omegasome formation, substrate recognition, lysosomal acidity and autophagosome membrane nucleation.A recent report from Zhang and co-workers indicates that treatment of an amyotrophic lateral sclerosis (ALS) mouse model with rapamycin actually exacerbates neuronal loss and disease progression, associated with enhanced apoptosis. This study reflects the need for a better understanding of the contribution of autophagy to ALS and other neurodegenerative diseases since this pathway may not only operate as a cleaning-up mechanism. Then, autophagy impairment may be part of the pathological mechanisms underlying the disease, whereas augmenting autophagy levels above a certain threshold could lead to detrimental effects in neuronal function and survival.

2011 Mar 16 - Rodríguez de Rivera FJ, Oreja Guevara C, Sanz Gallego I, San José Valiente B, Santiago Recuerda A, Gómez Mendieta MA, Arpa J, Díez Tejedor E

Unidad de ELA, Servicio de Neurología, Hospital Universitario La Paz, IDIPAZ, Universidad Autónoma de Madrid, Madrid, España.

Neurologia (Barcelona, Spain)

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a disease with very poor prognosis, and a mortality of 50% at 18 months after diagnosis. Multidisciplinary units attempt to improve the quality of life and survival of patients with ALS.The aim of this study is to evaluate every 3 months, over a 24-month period, the outcome of patients treated at the ALS unit since the time of diagnosis. MATERIAL AND METHODS: We performed a prospective observational study of patients treated in the ALS unit following a clinical pathway since the time of diagnosis with quarterly reviews from 2006 to 2010. The age of onset, functional impairment (ALSFRS-r), impairment of respiratory function, dysphagia and signs of depression and/or cognitive impairment were evaluated in relation to the initial location symptoms (bulbar [B], upper limbs [UL], lower limbs [LL]). RESULTS: A total of 42 patients (30 males and 12 females) were evaluated (mean age at onset of 57.97years old, SD 14.56).

2011 Mar - Pizzuti A, Petrucci S

Università di Roma "Sapienza" Dipartimento di Medicina Sperimentale - Istituto CSS-Mendel. a.pizzuti@css-mendel.it.

Archives italiennes de biologie

Recent studies on patient with sporadic ALS and on in vitro and in vivo models of mendelian diseases have been addressed toward the unravelling of the mitochondrial behaviour in ALS, whether as a primarily pathogenic factor, or as a fundamental contributor to the cell death. Morphological evidence suggests mitochondria pathology in ALS and many physiological mechanisms involving these organelles appear deranged in ALS, such as energy production, apoptotic triggering, calcium homeostasis and axonal transport of mitochondria. The article briefly addresses recent advances on this field.

2011 Mar - Inghilleri M, Iacovelli E

Department of Neurological Sciences - University of Rome "Sapienza". maurizio.inghilleri@uniroma1.it.

Archives italiennes de biologie

EMG abnormalities are frequent and these include fibrillation potentials or positive sharp wave potentials, or both, with fasciculation potentials in resting muscle, and an incomplete interference pattern, with abnormal motor unit potentials.Collateral or terminal nerve sprouting is common in ALS and is frequent large macro-motor unit potentials (MUPs). Motor unit number estimation (MUNE) may be useful in measuring loss of functioning motor units and is an attractive endpoint measure in clinical drug trials in ALS because it directly assesses loss of lower motor neurons and is sensitive to disease progression. Transcortical magnetic stimulation protocols, and cortical excitability may be useful to assess the involvement of upper motor neuron system. In this chapter the advantages, limitations and promise of these various methods are discussed, in order to indicate the direction for further neurophysiological studies in this disorder.