Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector55410.25692/ACEN.2018.4.11TechnologiesТехнологииUnknownDiagnostics and management techniques in respiratory disorders in amyotrophic lateral sclerosisМетоды диагностики и коррекции респираторных нарушений при боковом амиотрофическом склерозеVasil’yevAleksey V.ВасильевАлексей Владимирович
Russian Federation
dr-ves@yandex.ruEliseyevaDariya D.ЕлисееваДарья Дмитриевна
Russian Federation
dr-ves@yandex.ruIvanovaMaria V.ИвановаМария Васильевна
Russian Federation
dr-ves@yandex.ruKocherginIvan A.КочергинИван Александрович
Russian Federation
dr-ves@yandex.ruZakroyshchikovaInessa V.ЗакройщиковаИнесса Владимировна
Russian Federation
dr-ves@yandex.ruBrylevLev V.БрылевЛев Вадимович
Russian Federation
dr-ves@yandex.ruShtabnitskiyVasily A.ШтабницкийВасилий Андреевич
Russian Federation
dr-ves@yandex.ruZakharovaMaria N.ЗахароваМария Николаевна
Russian Federation
dr-ves@yandex.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»Research Сenter of NeurologyФГБНУ «Научный центр неврологии»Moscow Сity Сlinical Нospital named after V.M. BuyanovГБУЗ «Городская клиническая больница им. В.М. Буянова»Pirogov Russian National Research Medical UniversityФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова»07122018124768514122018Copyright ©; 2018, Vasil’yev A.V., Eliseyeva D.D., Ivanova M.V., Kochergin I.A., Zakroyshchikova I.V., Brylev L.V., Shtabnitskiy V.A., Zakharova M.N.Copyright ©; 2018, Vasil’yev A.V., Eliseyeva D.D., Ivanova M.V., Kochergin I.A., Zakroyshchikova I.V., Brylev L.V., Shtabnitskiy V.A., Zakharova M.N.2018Vasil’yev A.V., Eliseyeva D.D., Ivanova M.V., Kochergin I.A., Zakroyshchikova I.V., Brylev L.V., Shtabnitskiy V.A., Zakharova M.N.Vasil’yev A.V., Eliseyeva D.D., Ivanova M.V., Kochergin I.A., Zakroyshchikova I.V., Brylev L.V., Shtabnitskiy V.A., Zakharova M.N.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/554

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease characterized by relentless increase in weakness of limb and respiratory muscles. Whereas the etiology is still not clear, there have been a remarkable progress in understanding ALS pathogenesis and pathophysiology over the last years. In 2017 the second drug that can alter ALS progression rate has been registered. Nevertheless, the prognosis remains very poor and the average life expectancy in ALS does not exceed 5 years. The most common causes of death in ALS are respiratory complications and respiratory failure. Consequently, monitoring of the respiratory system function in ALS patients by neurologists and pulmonologists is crucial for survival and prolongation of life in this condition. Currently the most available diagnostic tool for the assessment of the respiratory profile in ALS is spirometry. Other methods, such as measurement of sniff nasal pressure, overnight oximetry and polysomnography, are also important but, due to technical complexity, their use in routine practice is limited. The principal method of respiratory support used in ALS is noninvasive lung ventilation (NIV). It can increase the average life expectancy and improve the patients’ quality of life. Invasive lung ventilation with endotracheal tube is another technique that can increase life expectancy and improve quality of life. However, the number of patients accepting this type of mechanical ventilation is very low. Multidisciplinary approach involving different medical specialists including neurologists, pulmonologists and critical care physicians is the key to successive management of ALS patients with respiratory disorders.

Боковой амиотрофический склероз (БАС) – быстро прогрессирующее заболевание, сопровождающееся неуклонным нарастанием слабости мышц конечностей и дыхательной мускулатуры. Этиология заболевания до конца не ясна, однако в последние годы удалось значительно продвинуться в понимании патогенеза и патофизиологии БАС. Разработаны препараты, снижающие скорость прогрессии БАС. Несмотря на это прогноз остается крайне неблагоприятный, а средняя продолжительность жизни пациентов с БАС составляет не более 5 лет. Наиболее частыми причинами гибели больных являются дыхательная недостаточность и респираторные осложнения. В статье рассмотрены патофизиология дыхательных нарушений при БАС и методы оценки функции дыхания. Основным методом респираторной поддержки больных БАС, который позволяет увеличивать среднюю продолжительность жизни и улучшать качество жизни пациентов, является неинвазивная вентиляция легких. Залогом для успешного ведения пациентов с БАС, имеющих респираторные проблемы, является мультидисциплинарный подход с привлечением врачей разных специальностей – неврологов, пульмонологов, реаниматологов.

amyotrophic lateral sclerosisrespiratory disordersnoninvasive ventilationinvasive ventilationбоковой амиотрофический склероздыхательные нарушениянеинвазивная вентиляцияинвазивная вентиляцияRowland L.P., Shneider N.A. Amyotrophic lateral sclerosis. N Engl J Med 2001; 344: 1688–1700. DOI: 10.1056/NEJM200105313442207. PMID: 11386269.Strong M.J., Grace G.M., Freedman M. et al. Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2009; 10: 131–146. DOI: 10.1080/17482960802654364. PMID: 19462523.Tandan R., Bradley W.G. Amyotrophic lateral sclerosis: part 1. Clinical features, pathology, and ethical issues in management. Ann Neurol 1985; 18: 271–280. DOI: 10.1002/ana.410180302. PMID: 4051456.de Carvalho M., Matias T., Coelho F. et al. Motor neuron disease presenting with respiratory failure. J Neurol Sci 1996; 139: 117–122. DOI: 10.1016/0022-510X(96)00089-5. PMID: 8899670.Marangi G., Traynor B.J. Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges. Brain Res 2015; 1607: 75–93. DOI: 10.1016/j.brainres.2014.10.009. PMID: 25316630.Renton A.E., Chio A., Traynor B.J. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 2014; 17: 17–23. DOI: 10.1038/nn.3584. PMID: 24369373.Brown R.H., Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med 2017; 377: 162–172. DOI: 10.1056/NEJMra1603471. PMID: 28700839.Robberecht W., Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 2013; 14: 248–264. DOI: 10.1038/nrn3430. PMID: 23463272.Soriani M.H., Desnuelle C. Epidemiology of amyotrophic lateral sclerosis. Rev Neurol (Paris) 2009; 165: 627–640. DOI: 10.1016/j.neurol.2009.04.004. PMID: 19524991.Corcia P., Pradat P.F., Salachas F. et al. Causes of death in a post-mortem series of ALS patients. Amyotroph Lateral Scler 2008; 9: 59–62. DOI: 10.1080/17482960701656940. PMID: 17924236.Dash R.P., Babu R.J., Srinivas N.R. two decades-long journey from riluzole to edaravone: revisiting the clinical pharmacokinetics of the only two amyotrophic lateral sclerosis therapeutics. Clin Pharmacokinet 2018 [Epub ahead of print]. DOI: 10.1007/s40262-018-0655-4. PMID: 29682695.Wijdicks E.F.M. The neurology of acutely failing respiratory mechanics. Ann Neurol 2017; 81: 485–494. DOI: 10.1002/ana.24908. PMID: 28253561.Louwerse E.S., Visser C.E., Bossuyt P.M., Weverling G.J. Amyotrophic lateral sclerosis: mortality risk during the course of the disease and prognostic factors. The Netherlands ALS Consortium. J Neurol Sci 1997; 152: S10–S17. PMID: 9419048.Just N., Bautin N., Danel-Brunaud V. et al. The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle weakness in amyotrophic lateral sclerosis. Eur Respir J 2010; 35: 353–360. DOI: 10.1183/09031936.00184908. PMID: 19741023.Kuhnlein P., Gdynia H.J., Sperfeld A.D. et al. Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis. Nat Clin Pract Neurol 2008; 4: 366–374. DOI: 10.1038/ncpneuro0853. PMID: 18560390.Koritnik B., Azam S., Andrew C.M. et al. Imaging the brain during sniffing: a pilot fMRI study. Pulm Pharmacol Ther 2009; 22: 97–101. DOI: 10.1016/j.pupt.2008.10.009. PMID: 19028593.Shimizu T., Komori T., Kugio Y. et al. Electrophysiological assessment of corticorespiratory pathway function in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2010; 11: 57–62. DOI: 10.1080/17482960903207385.PMID: 19707909.de Carvalho M., Swash M. Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: a six-month longitudinal study. Muscle Nerve 2010; 41: 208–211. DOI: 10.1002/mus.21495. PMID: 19697379.Javad Mousavi S.A., Zamani B., Shahabi Shahmiri S. et al. Pulmonary function tests in patients with amyotrophic lateral sclerosis and the association between these tests and survival. Iran J Neurol 2014; 13: 131–137. PMID: 25422731.Gautier G., Verschueren A., Monnier A. et al. ALS with respiratory onset: clinical features and effects of non-invasive ventilation on the prognosis. Amyotroph Lateral Scler 2010; 11: 379–382. DOI: 10.3109/17482960903426543. PMID: 20001486.Kiernan M.C., Vucic S., Cheah B.C. et al. Amyotrophic lateral sclerosis. Lancet 2011; 377: 942–955. DOI: 10.1016/S0140-6736(10)61156-7. PMID: 21296405.Pinto S., Pinto A., De Carvalho M. Do bulbar-onset amyotrophic lateral sclerosis patients have an earlier respiratory involvement than spinal-onset amyotrophic lateral sclerosis patients? Eura Medicophys 2007; 43: 505–509. PMID: 18084174.Hardiman O. Management of respiratory symptoms in ALS. J Neurol 2011; 258: 359–365. DOI: 10.1007/s00415-010-5830-y. PMID: 21082322.Bach J.R., Bianchi C., Aufiero E. Oximetry and indications fortracheotomy for amyotrophic lateral sclerosis. Chest 2004; 126: 1502–1507. DOI: 10.1378/chest.126.5.1502. PMID: 15539719.Gonzalez-Bermejo J., Perrin C., Janssens J.P. et al. Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoringabnormal events occurring during non-invasive ventilation. Thorax 2012; 67: 546–552. DOI: 10.1136/thx.2010.142653. PMID: 20971982.Sherman M.S., Paz H.L. Review of respiratory care of the patient with amyotrophic lateral sclerosis. Respiration 1994; 61: 61–67. DOI: 10.1159/000196308. PMID: 8008989.Pellegrino R., Viegi G., Brusasco V. et al. Interpretative strategies for lung function tests. Eur Respir J 2005; 26: 948–968. DOI: 10.1183/09031936.05.00035205. PMID: 16264058.Qaseem A., Wilt T.J., Weinberger S.E. et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med 2011; 155: 179–191. DOI: 10.7326/0003-4819-155-3-201108020-00008. PMID: 21810710.Pruitt B. Loosening the bonds of restrictive lung disease. Nursing 2008; 38: 34–39. DOI: 10.1097/01.NURSE.0000327490.70569.bc. PMID: 18648298.Andersen P.M., Abrahams S., Borasio G.D. et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol 2012; 19: 360–375. DOI: 10.1111/j.1468-1331.2011.03501.x. PMID: 21914052.Miller R.G., Jackson C.E., Kasarskis E.J. et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73: 1218–1226. DOI: 10.1212/WNL.0b013e3181bc0141. PMID: 19822872.Lechtzin N., Rothstein J., Clawson L. et al. Amyotrophic lateral sclerosis: evaluation and treatment of respiratory impairment. Amyotroph Lateral Scler Other Motor Neuron Disord 2002; 3: 5–13. DOI: 10.1080/146608202317576480. PMID: 12061943.Czaplinski A., Yen A.A., Appel S.H. Forced vital capacity (FVC) as an indicator of survival and disease progression in an ALS clinic population. J Neurol Neurosurg Psychiatry 2006; 77: 390–392. DOI: 10.1136/jnnp.2005.072660. PMID: 16484652.Lechtzin N., Wiener C.M., Shade D.M. et al. Spirometry in the supine position improves the detection of diaphragmatic weakness in patients with amyotrophic lateral sclerosis. Chest 2002; 121: 436–442. DOI: 10.1378/chest.121.2.436. PMID: 11834654.Lechtzin N., Scott Y., Busse A.M. et al. Early use of non-invasive ventilation prolongs survival in subjects with ALS. Amyotroph Lateral Scler 2007; 8: 185–188. DOI: 10.1080/17482960701262392. PMID: 17538782.De Troyer A., Borenstein S., Cordier R. Analysis of lung volume restriction in patients with respiratory muscle weakness. Thorax 1980; 35: 603–610. DOI: 10.1136/thx.35.8.603. PMID: 7444828.Polkey M.I., Lyall R.A., Yang K. et al. Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med 2017; 195: 86–95. DOI: 10.1164/rccm.201604-0848OC. PMID: 27494149.Sferrazza Papa G.F., Pellegrino G.M., Di Marco F. et al. Predicting survival in amyotrophic lateral sclerosis: should we move forward from vital capacity? Am J Respir Crit Care Med 2017; 195: 144–145. DOI: 10.1164/rccm.201609-1838LE. PMID: 28035853.Lechtzin N. Respiratory effects of amyotrophic lateral sclerosis: problems and solutions. Respir Care 2006; 51: 871–81. PMID: 16867198.Tilanus T.B.M., Groothuis J.T., TenBroek-Pastoor J.M.C. et al. The predictive value of respiratory function tests for non-invasive ventilation in amyotrophic lateral sclerosis. Respir Res 2017; 18: 144. DOI: 10.1186/s12931-017-0624-8. PMID: 28743265.Lo Coco D., Mattaliano P., Spataro R. et al. Sleep-wake disturbances in patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2011; 82: 839–842. DOI: 10.1136/jnnp.2010.228007. PMID: 21217159.Arnulf I., Similowski T., Salachas F. et al. Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis. Am J Respir Crit Care Med 2000; 161: 849–856. DOI: 10.1164/ajrccm.161.3.9805008. PMID: 10712332.Pinto A., de Carvalho M., Evangelista T. et al. Nocturnal pulse oximetry: a new approach to establish the appropriate time for non-invasive ventilation in ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4: 31–35. DOI: 10.1080/14660820310006706. PMID:12745616.Ahmed R.M., Newcombe R.E., Piper A.J. et al. Sleep disorders and respiratory function in amyotrophic lateral sclerosis. Sleep Med Rev 2016; 26: 33–42. DOI: 10.1016/j.smrv.2015.05.007. PMID: 26166297.Quaranta V.N., Carratu P., Damiani M.F. et al. The prognostic role of obstructive sleep apnea at the onset of amyotrophic lateral sclerosis. Neurodegener Dis 2017; 17: 14–21. DOI: 10.1159/000447560. PMID: 27595268.Bourke S.C., Gibson G.J. Sleep and breathing in neuromuscular disease. Eur Respir J 2002; 19: 1194–1201. DOI: 10.1183/09031936.02.01302001a. PMID: 12108875.Elman L.B., Siderowf A.D., McCluskey L.F. Nocturnal oximetry: utility in the respiratory management of amyotrophic lateral sclerosis. Am J Phys Med Rehabil 2003; 82: 866–870. DOI: 10.1097/01.PHM.0000091985.22659.30. PMID: 14566155.Katzberg H.D., Selegiman A., Guion L. et al. Effects of noninvasive ventilation on sleep outcomes in amyotrophic lateral sclerosis. J Clin Sleep Med 2013; 9: 345–351. DOI: 10.5664/jcsm.2586. PMID: 23585750.Vrijsen B., Buyse B., Belge C. et al. Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a prospective polysomnographic study. J Clin Sleep Med 2015; 11: 559–566. DOI: 10.5664/jcsm.4704. PMID: 25766713.Lo Coco D., Piccoli F., La Bella V. Restless legs syndrome in patients with amyotrophic lateral sclerosis. Mov Disord 2010; 25: 2658–2661. DOI: 10.1002/mds.23261. PMID: 20669314.Vitacca M., Clini E., Facchetti D. et al. Breathing pattern and respiratory mechanics in patients with amyotrophic lateral sclerosis. Eur Respir J 1997; 10: 1614–1621. PMID: 9230256.Borasio G.D., Gelinas D.F., Yanagisawa N. Mechanical ventilation in amyotrophic lateral sclerosis: a crosscultural perspective. J Neurol 1998; 245: S7–S12. PMID: 9747928.Hopkins L.C., Tatarian G.T., Pianta T.F. Management of ALS: respiratory care. Neurology 1996; 47: S123–S125. PMID: 8858068.Pinto A.C., Evangelista T., Carvalho M. et al. Respiratory assistance with a noninvasive ventilator (Bipap) in MND/ALS patients – survival rates in a controlled trial. J Neurol Sci 1995; 129: 19–26. PMID: 7595610.Aboussouan L.S., Khan S.U., Meeker D.P. et al. Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis. Ann Intern Med 1997; 127: 450–3. DOI: 10.7326/0003-4819-127-6-199709150-00006. PMID: 9313002.Andersen P.M., Borasio G.D., Dengler R. et al. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives; An evidence-based review with good practice points. Eur J Neurol 2005; 12: 921–938. DOI: 10.1111/j.1468-1331.2005.01351.x. PMID: 16324086.Zavalishin I.A., Zakharova M.N. [Amyotrophic lateral sclerosis]. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova 1999; 4: 60–64. (In Russ.)Завалишин И.А., Захарова М.Н. Боковой амиотрофический склероз. Журнал неврологии и психиатрии им. C.C. Корсакова 1999; 4: 60–4.Kaub-Wittemer D., Steinbuchel N., Wasner M. et al. Quality of life and psychococial issues in ventilated patients with amyotrophic lateral sclerosis and their caregivers. J Paint Symptom Manage 2003; 26: 890–896. DOI: 10.1016/S0885-3924(03)00323-3. PMID: 14527757.McDermott C.J., Bradburn M.J., Maguire C. et al. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol 2015; 14: 883–892. DOI: 10.1016/S1474-4422(15)00152-0. PMID: 26234554.Onders R.P., Elmo M., Khansarinia S. et al. Complete worldwide operative experience in laparoscopic diaphragm pacing: results and differences in spinal cord injured patients and amyotrophiclateral sclerosis patients. Surg Endosc 2009, 23: 1433–1440. DOI: 10.1007/s00464-008-0223-3. PMID: 9747928.Popova L.M. Bokovoy amiotroficheskiy scleroz v usloviyakh prodlennoy zhizni [Amyotrophic lateral sclerosis in prolongued life]. Moscow, 1998. 144 p. (In Russ.)Попова Л.М. Боковой амиотрофический склероз в условиях продленной жизни. М., 1998. 144 с.LeBon B., Fisher S. Case report: Maintaining and withdrawing long-term invasive ventilation in a patient with MND/ALS in a home setting. Palliat Med 2011; 25: 262–5. DOI: 10.1177/0269216310389224. PMID: 21228095.Vianello A., Arcaro G., Palmieri A. et al. Survival and quality of life after tracheostomy for acute respiratory failure in patients with amyotrophic lateral sclerosis. J Crit Care 2011; 26: 329. e7-14. DOI: 10.1016/j.jcrc.2010.06.003. PMID: 20655697.Albert S.M., Whitaker A., Rabkin J.G. et al. Medical and supportive care among people with ALS in the months before death or tracheostomy. J Pain Symptom Manage 2009; 38: 546–53. DOI: 10.1016/j.jpainsymman.2008.11.013. PMID: 19540088.Gelinas D.F., O’Connor P., Miller R.G. Quality of life for ventilator-dependent ALS patients and their caregivers. J Neurol Sci 1998; 160: S134–6. DOI: 10.1016/S0022-510X(98)00212-3. PMID: 9851663.Takei K., Tsuda K., Takahashi F. et al. An assessment of treatment guidelines, clinical practices, demographics, and progression of disease among patients with amyotrophic lateral sclerosis in Japan, the United States, and Europe. Amyotroph Lateral Scler Frontotemporal Degener 2017; 18: 88–97. DOI: 10.1080/21678421.2017.1361445. PMID: 28872912.Heritier Barras A.C., Adler D., Iancu Ferfoglia R. et al. Is tracheostomy still an option in amyotrophic lateral sclerosis? Reflections of a multidisciplinary work group. Swiss Med Wkly 2013; 143: w13830. DOI: 10.4414/smw.2013.13830. PMID: 23925784.Filart R.A., Bach J.R. Pulmonary physical medicine interventions for elderly patients with muscular dysfunction. Clin Geriatr Med 2003; 19: 189–204, viii–ix. DOI: 10.1016/S0749-0690(02)00066-6. PMID: 12735122.Hanayama K., Ishikawa Y., Bach J.R.. Amyotrophic lateral sclerosis. Successful treatment of mucous plugging by mechanical insufflation-exsufflation. Am J Phys Med Rehabil 1997; 76: 338–339. PMID: 9267195.Lechtzin N., Wolfe L.F., Frick K.D. The impact of high-frequency chest wall oscillation on healthcare use in patients with neuromuscular diseases. Ann Am Thorac Soc 2016; 13: 904–909. DOI: 10.1513/AnnalsATS.201509-597OC. PMID: 26999271.Bach J.R. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory AIDS. Chest 2002; 122: 92–98. DOI: 10.1378/chest.122.1.92. PMID: 12114343.Mustfa N., Aiello M., Lyall R.A. et al. Cough augmentation in amyotrophic lateral sclerosis. Neurology 2003; 6: 1285–1287. DOI: 10.1212/01.WNL.0000092018.56823.02. PMID: 14610141.Clemens K.E., Klaschik E. Symptomatic therapy of dyspnoea with strong opioids and its effect on ventilation in palliative care patients. J Pain Symptom Manage 2007; 33: 473–481. DOI: 10.1016/j.jpainsymman.2006.09.015. PMID:17397708.Moosavi S.H., Golestanian E., Binks A.P. et al. Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans. J Appl Physiol 2003; 94: 141–154. DOI: 10.1152/japplphysiol.00594.2002. PMID: 12391041.Clemens K.E., Klaschik E. Morphine in the management of dyspnoea in ALS. A pilot study. Eur J Neurol 2008; 15: 445–450. DOI: 10.1111/j.1468-1331.2008.02102.x. PMID: 18355309.Andersen P.M., Borasio G.D., Dengler R. et al. Good practice in the management of amyotrophic lateral sclerosis: clinical guidelines. An evidence-based review with good practice points. EALSC Working Group. Amyotroph Lateral Scler 2007; 8: 195–213. DOI: 10.1080/17482960701262376. PMID: 17653917.Ferreira D.H., Silva J.P., Quinn S. et al. Blinded Patient Preference for Morphine Compared to Placebo in the Setting of Chronic Refractory Breathlessness – An Exploratory Study. J Pain Symptom Manage 2016; 51: 247–254. DOI: 10.1016/j.jpainsymman.2015.10.005. PMID: 26598037.Simon S.T., Higginson I.J., Booth S. et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2016; 10: CD007354. DOI: 10.1002/14651858.CD007354.pub3. PMID: 27764523.