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Amyotrofik Lateral Skleroz: Klinik Özellikler ve Güncel Tedavi Yaklaşımları

Amyotrofik lateral skleroz, ayrıca Lou Gehring hastalığı olarak da bilinir, primer korteks, beyinsapı ve spinal kordda motor nöron dejenerasyonu ile karakterize en sık görülen motor nöron hastalığıdır. Bu tutulum sonucu yaygın paralizi, solunum yetmezliği ve hastalık başlangıcından ortalama 3-5 yıl içinde ölüme yol açar. Vakaların çoğu sporadiktir ve sadece %10’unda aile öyküsü vardır. Son yıllarda nörodejenerasyon alanında en ilginç keşiflerden biri frontotemporal demans, amyotrofik lateral skleroz ve iki hastalığın birlikteliğinin nedeni olarak düşünülen C9orf72 (chromosome 9 open reading frame 72) mutasyonudur. Günümüzde amyotrofik lateral skleroz için küratif tedavi yoktur. Şimdiye kadar tek bir ilaç, Riluzol, amyotrofik lateral skleroz'da sağ kalımı uzatmayı, yaklaşık 3-5 ay, başarabilmiştir. Araştırmacılar bilinen patofizyolojik yolaklar ve genetik defektleri hedef alarak hastalık ilerleyişini durdurmayı hedeflemektedirler. Sadece semptomatik bakım yaşam kalitesini ve sağ kalımı artırmak için önerilmektedir. Solunum ve beslenme desteği; disfaji ve gastrostomi kontrolü; iletişim ve mobilite programları; spastisitenin önlenmesi; ağrı medikasyonu; kognitif disfonksiyon, depresyon ve duygudurum bozukluklarının (özellikle apati) kontrolü, yorgunluk, uyku bozukluğu ve derin ven trombozunun önlenmesini içermektedir.

Anahtar Kelimeler:

Motor nöron hastalıkları, amyotrofik lateral skleroz, frontotemporal demans, riluzol, tedavi

Amyotrophic lateral sclerosis: clinical features and current treatment approaches

Amyotrophic lateral sclerosis also known as Lou Gehring’s disease, is the most common motor neuron disease characterized by motor neuron degeneration in the primary cortex, brainstem and spinal cord. This leads to widespread paralysis, respiratory insufficiency and death within an average of 3-5 years from disease onset. Majority of cases is sporadic and only 10% have a family story. One of the most interesting discovery in the field of neurodegeneration in recent years is genetic mutation in the C9orf72 (chromosome 9 open reading frame 72) gene, the most common mutation found to be causative of frontotemporal dementia, amyotrophic lateral sclerosis and concomitant of these two diseases. Currently curative therapy for amyotrophic lateral sclerosis is lacking. To date, one medication, Riluzole, has been proved to prolong survival, approximately 3-5 months, in amyotrophic lateral sclerosis. Researches aim to slow disease progression by targeting known pathophysiological pathways or genetics defects. Only symptomatic care to improve quality of life and survival is suggested. These includes respiratory and nutrition support; dysphagia and gastrostomy management; communication and mobility programs; spasticity prevention; pain medication; management of cognitive dysfunction, depression, mood dysorders (especially apathy), fatigue, sleep disturbance and prevention of deep venous thrombosis.

Keywords:

Motor neuron diseases, amyotrophic lateral sclerosis, frontotemporal dementia, riluzole, treatment,

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Gordon PH. Amyotrophic lateral sclerosis: an update for 2013 clinical features, pathophysiology, management and therapeutic trials. Aging Dis. 2013;4:295-310.
Bali T, Miller TM. Management of amyotrophic lateral sclerosis. Mo Med. 2013;110(5):417-21.
Gordon P, Corcia P, Meininger V. New therapy options amyotrophic lateral sclerosis. Expert Opin Pharmacother. 2013;14:1907-17.
Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literatüre. Neuroepidemiology. 2013;41:118-30.
Lebnond CS, Kaneb HM, Dion PA, Rouleau GA. Dissection of genetic factors associated with amyotrophic lateral sclerosis. Exp Neurol. 2014;262PB:91-101.
Renton AE, Chio A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17:17-23.
Van Damme P, Robberecht W. Clinical implications of recent breakthroughts in amyotrophic lateral sclerosis. Curr Opin Neurol. 2013;26:466-72.
Sreedharan J, Brown RH Jr. Amyotrophic lateral sclerosis: problems and prospects. Ann Neurol. 2013;74:309-16.
Rizzo F, Riboldi G, Salani S, Nizzardo M, Simone C, Corti S et al. Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci. 2014;71:999-1015.
Trojsi F, Monsurro MR, Tedeschi G. Exposure to environmental toxicants and pathogenesis of amyotrophic lateral sclerosis: state of the art and research perspectives. Int J Mol Sci. 2013;14:15286-311.
Modgil S, Lahiri DK, Sharma VL, Anand A. Role of early life exposure and environment on neurodegeneration: implications on brain disorders. Transl Neurodegener. 2014;(3):9.
Chio A, Battistini S, Calvo A, Caponnetto C, Conforti FL, Corbo M et al. Genetic counselling in ALS: facts, uncertainties and clinical suggestions. J Neurol Neurosurg Psychiatry. 2014;85:478-85.
Bennion Callister J, Pickering-Brown SM. Pathogenesis/genetics of frontotemporal dementia and how it relates to ALS. Exp Neurol. 2014;262PB:84-90.
Vucic S, Rothstein JD, Kiernan MC. Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies. Trends Neurosci. 2014;37:433-42.
Ahuja A, Dev K, Tanwar RS, Selwal KK, Tyagi PK. Copper mediated neurological disorder: vision into amyotrophic lateral sclerosis, Alzheimer and Menkes disease. J Trace Elem Med Biol. 2014;29C:11-23.
Beghi E. Are Professional soccer players at higher risk for ALS? Amyotrophic Lateral Scler Frontotemporal Degener. 2013;14:501-6.
Anand A, Thakur K, Gupta PK. ALS and oxidative stress: the neurovascular scenario. Oxid Med Cell Longev. 2013;2013:635831.
Pollari E, Goldsteins G, Bart G, Koistinaho J, Giniatullin R. The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis. Front Cell Neurosci. 2014;(8):131.
Pandya RS, Zhu H, Li W, Bowser R, Friedlander RM, Wang X. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis. Cell Mol Life Sci. 2013;70:4729-45.
Valori CF, Brambilla L, Martorana F, Rossi D. The multifaceted role of glial cells in amyotrophic lateral sclerosis. Cell Mol Life Sci. 2014;71:287-97.
Garbuzova-Davis S, Sanberg PR. Blood-CNS barrier impairment in ALS patients versus an animal model. Front Cell Neurosci. 2014;(8):21.
Heath PR, Kirby J, Shaw PJ. Investigating cell death mechanisms in amyotrophic lateral sclerosis using transcriptomics. Front Cell Neurosci. 2013;(7):259.
van Groenestijn AC, van de Port IG, Schröder CD, Post MW, Grupstra HF, Kruitwagen ET et al. Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial. BMC Neurol. 2011;(11):70.
Thomsen GM, Gowing G, Svendsen S, Svendsen CN. The past, present and future of stem cell clinical trials for ALS. Exp Neurol. 2014;262PB:127-137.
Fecto F, Siddique T. Making connections: pathology and genetics link amyotrophic lateral sclerosis with frontotemporal lobe dementia. J Mol Neurosci. 2011;45:663-75.
Lillo P, Mioshi E, Zoing MC, Kiernan MC, Hodges JR. How common are behavioural changes in amyotrophic lateral sclerosis? Amyotroph Lateral Scler. 2011;12:45-51.
Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology. 2005;65:586-90.
Lillo P, Savage S, Mioshi E, Kiernan MC, Hodges JR. Amyotrophic lateral sclerosis and frontotemporal dementia: A behavioural and cognitive continuum. Amyotroph Lateral Scler. 2012;13:102-9.
Abrahams S, Newton J, Niven E, Foley J, Bak TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:9-14.
Misawa S. Utility of muscle ultrasonography for the diagnosis of amyotrophic lateral sclerosis. Brain Nerve. 2014;66:229-36.
Foerster BR, Welsh RC, Feldman EL. 25 years of neuroimaging in amyotrophic lateral scleosis. Nat Rev Neurol. 2013;9:513-24.
Senda J, Kato S, Kaga T, Ito M, Atsuta N, Nakamura T et al. Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study. Amyothroph Lateral Scler. 2011;12:59-69.
Tan RH, Devenney E, Dobson-Stone C, Kwok JB, Hodges JR, Kiernan MC et al. Cerebellar integrity in the amyotrophic lateral sclerosis - frontotemporal dementia continuum. PLoS One. 2014;9:105632.
Sarac H, Zagar M, Vranjes D, Henigberg N, Bilic E, Pavlisa G. Magnetic resonance imaging and magnetic resonance spectroscopy in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. Coll Antropol. 2008;32:205-10.
Lillo P, Mioshi E, Burrell JR, Kiernan MC, Hodges JR, Hornberg M. Grey and white matter changes across the amyotrophic lateral sclerosis-frontotemporal dementia continiuum. PLoS One. 2012;7:e43993.
Ambikairajah A, Devenney E, Flanagan E, Yew B, Mioshi E, Kiernan MC et al. A visual MRI atrophy rating scale for the amyotrophic lateral sclerosis-frontotemporal dementia continuum. Amyotroph Lateral Scier Frontotemporal Degener. 2014;15:226-34.
Blasco H, Corcia P, Pradat PF What are the applications of biomarkers in ALS today?. Presse Med. 2014;43:569-79.
Poppe L, Rue L, Robberecht W, Van Den Bosch L. Translating biological findings into new treatment strategies for amyotrophic lateral sclerosis (ALS). Exp Neurol. 2014 262PB:138-151.
Carter GT, Krivickas LS, Weydt P, Weiss MD, Miller RG. Drug therapy for amyotrophic lateral sclerosis: Where are we now? IDrugs. 2003;6:147-53.
Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Amyotroph Lateral Scler Other Motor Neuron Disord. 2003;4:191-206.
Current clinical trials and underlying pathomechanisms. Nervenarzt. 2008;79:653-61.
Meamar R, Nasr-Esfahani MH, Mousavi SA, Basiri K. Stem cell therapy in amyotrophic lateral sclerosis. J Clin Neurosci. 2013;20:1659-63.
Majmudar S, Wu J, Paganoni S. Rehabilitation in amyotrophic lateral sclerosis: why it matters. Muscle Nerve. 2014;50:4-13.
Janiszewski DW, Caroscio JT, Wisham LH. Amyotrophic lateral sclerosis: a comprehensive rehabilitation approach. Arch Phys Med Rehabil. 1983;64:304-7.
Jenkins TM, Hollinger H, McDermott CJ. The evidence for symptomatic treatments in amyotrophic lateral sclerosis. Curr Opin Neurol. 2014. doi: 10.1097/WCO.00000000000000135.
Zhao W, Beers DR, Appel SH. Immune-mediated mechanism in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol. 2013;8:888-99.
Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013;9:617-28.
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