What are the guideline sources, guidelines and references for Amyotrophic lateral sclerosis ?
Guideline sources The following summarized guidelines for the evaluation and management of amyotrophic lateral sclerosis are prepared by our editorial team based on guidelines from the American College of Chest Physicians (ACCP 2023), the Infectious Diseases Society of America (IDSA/ACR/AAN 2021), the ALS Society of Canada (ALSSC 2020), the European Federation of Neurological Societies (EFNS 2012), and the American Academy of Neurology (AAN 2009). 1 2 3 4 5 6 7 7 8 9 9 9 Definition ALS is a progressive neurological disorder characterized by degeneration of upper motor and lower motor neurons. 7 Epidemiology ALS is familial (10%) and sporadic (90%) in origin. The pathological hallmark of ALS is the presence of inclusion bodies (aggregation of cytoplasmic proteins) in motor neurons. 9 9 Pathophysiology In the United States, the estimated prevalence of ALS is 5.2 persons per 100,000 persons. 8 https://web.pathway.md/diseases/recoWND9TN3ZBmenp 1/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Disease course Spinal motor neuron degeneration results in muscular paralysis, including respiratory muscle paralysis. Motor neuron degeneration can also occur in the frontal cortex, causing frontotemporal degeneration and dementia. 9 Prognosis and risk of recurrence The overall survival of patients with ALS is approximately 3 years after the time of diagnosis. 7 Calculator Calculator Revised Amyotrophic Lateral Scl Revised El Escorial diagnostic cr Guidelines 1. Screening and diagnosis Diagnosis: Confirm the diagnosis of ALS by a neurologist or physical medicine and rehabilitation specialist with training and expertise in ALS. E Refer patients with an initial diagnosis of ALS to an ALS specialty clinic for confirmation of diagnosis within 4 weeks. E Differential diagnosis: As per IDSA 2021 guidelines, do not test for Lyme disease routinely in patients with typical ALS. D As per EFNS 2012 guidelines: Refer patients with suspected ALS to an experienced neurologist. E Review the diagnosis of ALS if there is no evidence of typical progression or the patient develops atypical features. E Communication of diagnosis: As per ALSSC 2020 guidelines, tailor the approach of communicating the diagnosis to the patient's individual needs. E As per EFNS 2012 guidelines, communicate the diagnosis to patients by a consultant with a good knowledge of the patient. E Show 8 more 2. Diagnostic investigations https://web.pathway.md/diseases/recoWND9TN3ZBmenp 2/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway History and physical examination: obtain prompt detailed clinical and paraclinical evaluations in all patients with suspected ALS. Consider obtaining additional investigations in selected patients, and repeating investigations if initial tests are equivocal. E Evaluation of respiratory function: As per ACCP 2023 guidelines, obtain pulmonary function testing to assist with management decisions in patients with neuromuscular disease at risk for respiratory complications. E Show 3 more As per ALSSC 2020 guidelines, obtain regular respiratory monitoring at baseline and every 3 months, or as clinically indicated, in patients with ALS, including: review of symptoms including dyspnea, orthopnea, and morning headaches B measurement of sitting FVC or slow vital capacity B sniff nasal inspiratory pressure, supine FVC, and/or maximal inspiratory pressure B arterial blood gases, venous blood gas, or transcutaneous CO when hypercapnia is suspected or when bulbar impairment precludes accurate testing B peak cough flow measurement to assess cough effectiveness B nocturnal oximetry or overnight polysomnography when symptomatic sleep-disordered breathing is suspected and other daytime indications for noninvasive ventilation initiation are not present. B As per EFNS 2012 guidelines, assess symptoms or signs of respiratory insufficiency, including symptoms of nocturnal hypoventilation, at each visit. E Show 3 more As per AAN 2009 guidelines, consider obtaining nocturnal oximetry to detect hypoventilation regardless of the FVC. C Show 2 more Cognitive evaluation: As per ALSSC 2020 guidelines: Screen for cognitive and behavioral impairment in patients with ALS early in their disease. B Obtain specific assessments with the patient and their family members or caregivers, as appropriate, if there is concern about cognition or behavior at any point. E As per EFNS 2012 guidelines, recognize that frontotemporal syndrome occurs in up to half of patients with ALS B and is associated with a poorer prognosis. Recognize that symptoms of cognitive dysfunction may appear before or after the onset of motor symptoms. Show 6 more As per AAN 2009 guidelines, consider screening for cognitive and behavioral impairment in patients with ALS, as many patients with ALS demonstrate cognitive impairment and may meet the criteria for dementia. C As per AAN 2009 guidelines: Consider screening for cognitive and behavioral impairment in patients with ALS. C https://web.pathway.md/diseases/recoWND9TN3ZBmenp 3/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Consider obtaining screening tests of executive function to detect cognitive impairment in patients with ALS before confirmation with formal neuropsychological evaluation. C Genetic testing: obtain genetic testing only in patients with a known family history of ALS and in sporadic ALS cases with the characteristic phenotype of the recessive D90A mutation. Do not obtain genetic testing in patients with sporadic ALS with a typical classical ALS phenotype. E Show 3 more Screening for venous thrombosis: recognize that there is an increased risk of VTE in patients with ALS and the risk appears heightened in cases with leg onset and in patients with poor mobility. E Show 2 more 3. Respiratory support Supplemental oxygen: As per ALSSC 2020 guidelines, do not administer oxygen routinely for chronic respiratory insufficiency. Assess the etiology of the hypoxia and consider administering supplemental oxygen if hypoxemia remains after optimal noninvasive ventilation pressure is provided. D As per EFNS 2012 guidelines, avoid using oxygen monotherapy because of the risk of exacerbating CO retention and oral dryness. Administer oxygen only in the presence of symptomatic hypoxia. D Noninvasive ventilation: As per ACCP 2023 guidelines, initiate noninvasive ventilation in patients with chronic respiratory failure. B Show 4 more As per ALSSC 2020 guidelines, intitiate noninvasive ventilation as the standard of care for the treatment of respiratory insufficiency in patients with ALS, both to lengthen survival and treat symptoms. B Show 9 more As per EFNS 2012 guidelines: Prefer noninvasive positive pressure ventilation over invasive mechanical ventilation in patients with symptoms or signs of respiratory insufficiency. E Recognize that noninvasive positive pressure ventilation can prolong survival for many months A and improve quality of life. B Consider providing active management of secretions and cough-assist devices to increase the effectiveness of assisted ventilation in patients with ALS. E As per AAN 2009 guidelines, consider initiating noninvasive ventilation for the treatment of respiratory insufficiency in ALS, both to lengthen survival and to slow the rate of FVC decline. C Invasive ventilation: https://web.pathway.md/diseases/recoWND9TN3ZBmenp 4/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway As per ACCP 2023 guidelines, consider offering invasive home mechanical ventilation via tracheostomy as an alternative to noninvasive ventilation in patients failing or intolerant of noninvasive ventilation (including extended daytime noninvasive ventilation use), worsening bulbar function, frequent aspiration, insufficient cough, episodes of chest infection despite adequate secretion management, or declining lung function. C As per ALSSC 2020 guidelines: Consider initiating invasive ventilation as an option in carefully selected patients when respiratory impairment cannot be effectively managed by noninvasive ventilation. E Consider performing a tracheostomy for upper airway obstruction with vocal cord paresis. Consider initiating long-term invasive ventilation. E As per EFNS 2012 guidelines, ensure an early discussion of end-of-life issues, coordination with palliative care teams, and appropriate advance directives to avoid unplanned (emergency) invasive mechanical ventilation. Initiate invasive mechanical ventilation only after informed discussion. E Weaning from ventilatory support: withdraw continuous ventilatory support only after consultation and planning with a healthcare professional with expertise in ventilation withdrawal and palliative sedation. E Show 2 more 4. Medical management General principles: As per ALSSC 2020 guidelines, refer patients with ALS to specialized ALS multidisciplinary clinics for optimized healthcare delivery. B Show 5 more As per EFNS 2012 guidelines, provide multidisciplinary care in all patients with ALS. Recognize that attendance at multidisciplinary clinics may extend survival, decrease medical complications, B and improve quality of life. B Show 3 more As per AAN 2009 guidelines, consider referring patients with ALS to multidisciplinary clinics to optimize healthcare delivery and prolong survival. C Riluzole: As per ALSSC 2020 guidelines, offer riluzole for improving survival in patients with ALS. A Initiate riluzole therapy soon after the diagnosis of ALS. Obtain regular monitoring of potential adverse effects. E As per EFNS 2012 guidelines, offer riluzole 50 mg BID in patients with ALS. A Show 3 more As per AAN 2009 guidelines, offer riluzole to slow disease progression in patients with ALS. A https://web.pathway.md/diseases/recoWND9TN3ZBmenp 5/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Edaravone: consider offering IV edaravone to slow the decline in the ALS Functional Rating Scale-Revised score in selected patients with ALS. C Insufficient evidence regarding the benefit of IV edaravone at other stages of ALS. Take into careful consideration and discuss individualized goals, risks, and benefits of IV edaravone before administration. E Management of sialorrhea, pharmacotherapy: As per ACCP 2023 guidelines, consider administering a therapeutic trial of an anticholinergic medication as first-line therapy, with continued use only if there are perceived benefits compared to side effects, for the management of sialorrhea in patients with neuromuscular diseases. C As per ALSSC 2020 guidelines, offer anticholinergic agents as first-line therapy for sialorrhea. Tailor individual medication choices to patient factors. Consider switching to another anticholinergic medication if one anticholinergic medication is ineffective. E As per EFNS 2012 guidelines, offer amitriptyline, oral or transdermal hyoscine, or sublingual atropine drops for the management of sialorrhea in patients with ALS. E Management of sialorrhea (oral suction): consider offering oral suction as an adjunct therapy. E Management of sialorrhea, botulinum toxin injection: As per ACCP 2023 guidelines, consider offering botulinum toxin therapy to salivary glands in patients with sialorrhea having an inadequate response or intolerant of the side effects of anticholinergic therapy. C As per ALSSC 2020 guidelines, consider offering botulinum toxin injections as second-line therapy B and after feeding tube insertion because of the theoretical risk of worsening swallowing or airway integrity. E As per EFNS 2012 guidelines, consider offering botulinum toxin injections into the parotid and/or submandibular gland in patients with refractory sialorrhea. C As per AAN 2009 guidelines, consider offering botulinum toxin B injection for the treatment of refractory sialorrhea. C Management of sialorrhea, radiotherapy: As per ACCP 2023 guidelines, consider offering salivary gland radiotherapy in patients with sialorrhea having an inadequate response or intolerant of the side effects of anticholinergic therapy. C As per ALSSC 2020 guidelines, consider offering focal salivary gland radiation as a second- or third-line therapy option in patients with sialorrhea. C As per EFNS 2012 guidelines, consider offering irradiation of the salivary glands when pharmacological treatment fails. E As per AAN 2009 guidelines, consider offering low-dose radiotherapy to the salivary glands for the treatment of refractory sialorrhea. C Management of sialorrhea (surgery): do not offer surgical interventions for the management of sialorrhea. D https://web.pathway.md/diseases/recoWND9TN3ZBmenp 6/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Management of dyspnea: Relieve anxiety and offer lorazepam (0.5-2.5 mg sublingually) for the management of short dyspneic bouts. Offer morphine (2.5 mg PO or SC) for longer phases of dyspnoea (> 30 minutes). E Offer morphine (2.5 mg PO 4-6 times daily) for the management of chronic dyspnea. Administer morphine SC or as IV infusion (started at 0.5 mg/hour, and titrated afterward) in patients with severe dyspnea. Add midazolam (2.5-5 mg) or diazepam if needed for nocturnal symptom control and to relieve anxiety. E Management of excessive bronchial secretions, manually assisted cough: As per ACCP 2023 guidelines, consider offering manually assisted cough techniques, independently or adding to other modalities (such as lung volume recruitment), in patients with reduced cough effectiveness. C As per ALSSC 2020 guidelines, offer manual-assisted coughing in patients reporting difficulty clearing airway secretions. E As per EFNS 2012 guidelines, teach patients and carers how to assist expiratory movements using a manual-assisted cough. E Management of excessive bronchial secretions, lung volume recruitment: As per ACCP 2023 guidelines: Consider offering glossopharyngeal breathing for lung volume recruitment and airway clearance in patients with hypoventilation. C Consider offering regular lung volume recruitment (breath stacking) using a handheld resuscitation bag or mouthpiece in patients with reduced lung function or cough effectiveness. C As per ALSSC 2020 guidelines, offer lung volume recruitment strategies in patients reporting difficulty clearing airway secretions. B Management of excessive bronchial secretions, mechanical insufflation-exsufflation: As per ACCP 2023 guidelines, consider adding regular mechanical insufflation-exsufflation (cough assist device) in patients with reduced cough effectiveness not adequately improved with alternative techniques. C As per ALSSC 2020 guidelines: Consider offering mechanical insufflation-exsufflation BID for secretion clearance in patients with reduced peak cough flow (< 270 L/min). Increase mechanical insufflation-exsufflation frequency during acute chest infections. E Provide in-home respiratory support of mechanical insufflation-exsufflation for education, titration, and troubleshooting. E As per EFNS 2012 guidelines, consider offering mechanical insufflator-exsufflator, particularly in the setting of an acute respiratory infection. E As per AAN 2009 guidelines, consider offering mechanical insufflation-exsufflation to clear secretions in patients with ALS having reduced peak cough flow, particularly during an acute https://web.pathway.md/diseases/recoWND9TN3ZBmenp 7/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway chest infection. C Management of excessive bronchial secretions, high-frequency chest wall oscillation: As per ACCP 2023 guidelines, consider offering high-frequency chest wall oscillation for secretion mobilization in patients with difficulties with secretion clearance. Consider combining high-frequency chest wall oscillation with airway clearance therapies, such as cough assistance or lung volume recruitment. C As per AAN 2009 guidelines, insufficient evidence to assess the risks and benefits of high- frequency chest wall oscillation for clearing airway secretions in patients with ALS. I Management of excessive bronchial secretions (home suction device and room humidifier): consider advising using a portable home suction device and a room humidifier. E Management of excessive bronchial secretions, pharmacotherapy: As per ALSSC 2020 guidelines, consider offering mucolytics (guaifenesin or N-acetylcysteine), -receptor antagonists (metoprolol or propranolol), nebulized saline, or nebulized ipratropium in patients with difficulties clearing airway secretions. E As per EFNS 2012 guidelines: Consider offering mucolytic agents (such as N-acetylcysteine 200-400 mg TID) for the management of excessive bronchial secretions in patients with ALS. E Consider offering combinations of -blockers and a nebulizer with saline and/or anticholinergic bronchodilators and/or mucolytics and/or furosemide. Offer mucolytics only if sufficient cough flow is present. E Management of pseudobulbar affect: As per ALSSC 2020 guidelines, counsel patients and family members that pseudobulbar affect is a symptom of ALS and does not necessarily represent a symptom of depression or impaired cognition. E Show 3 more As per EFNS 2012 guidelines, counsel patients and relatives that emotional lability is not a sign of an additional mood disorder but is because of the effects of ALS on the brain. E Show 2 more As per AAN 2009 guidelines, consider offering dextromethorphan plus quinidine for the treatment of pseudobulbar affect. C Management of fasciculations: do not offer medication management for fasciculations in most patients with ALS. D Consider offering gabapentin if fasciculations cause substantial distress. D Management of spasticity: As per ALSSC 2020 guidelines, consider offering stretching for the management of muscle spasticity. C Show 2 more As per EFNS 2012 guidelines: https://web.pathway.md/diseases/recoWND9TN3ZBmenp 8/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Consider offering regular physical therapy and antispastic drugs (such as baclofen and tizanidine) to relieve significant spasticity in patients with ALS. Consider offering hydrotherapy with exercises in warm pools (32-34 C) and cryotherapy. E Consider administering intrathecal baclofen in patients with severe spasticity despite oral medications. E Management of muscle cramps: As per ALSSC 2020 guidelines: Differentiate muscle cramps from other causes of pain. E Consider offering tonic water, gabapentin, and baclofen as first-line therapy for muscle cramps. Consider offering quinine, levetiracetam, and mexiletine as second-line treatment options. E As per EFNS 2012 guidelines: Consider offering levetiracetam for the management of muscle cramps in patients with ALS. Consider offering quinine sulfate (200 mg BID) if levetiracetam is unsuccessful or in case of side effects. E Consider offering physiotherapy, physical exercise, and/or hydrotherapy in the management of muscle cramps in patients with ALS. E Management of dysarthria: obtain regular monitoring in patients with dysarthria by a speech- language pathologist to ensure timely communication interventions. E Show 3 more Management of depression and anxiety: As per ALSSC 2020 guidelines: Treat depression in patients with ALS as it has a substantial impact on patient wellbeing. Consider offering SSRIs or SNRIs. Consider offering nonpharmacologic supportive measures, such as psychology, social work, psychiatry, or spiritual care. E Treat anxiety in patients with ALS as it has a substantial impact on patient wellbeing. Determine whether anxiety is related to respiratory insufficiency and treat it appropriately. Offer SSRIs in patients with concurrent depression. Recognize that benzodiazepines can exacerbate respiratory insufficiency. Consider offering nonpharmacologic supportive measures, such as psychology, social work, psychiatry, or spiritual care. E As per EFNS 2012 guidelines: Offer appropriate antidepressants (such as amitriptyline, SSRIs, or mirtazapine) for the management of depression in patients with ALS. Consider preferring SSRIs in elderly or cognitively impaired patients. E Offer bupropion or benzodiazepines (such as diazepam or lorazepam) for the management of anxiety in patients with ALS. E Management of insomnia and fatigue: As per ALSSC 2020 guidelines, obtain appropriate evaluation for insomnia as it may have multiple causes, such as respiratory insufficiency and depression. Consider obtaining respiratory investigations and sleep studies to determine the type and cause of insomnia. E https://web.pathway.md/diseases/recoWND9TN3ZBmenp 9/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway Show 4 more As per EFNS 2012 guidelines: Offer amitriptyline, mirtazapine, or appropriate hypnotics (such as zolpidem) for the management of insomnia in patients with ALS. E Consider offering modafinil for the management of debilitating fatigue in patients with ALS. B As per AAN 2009 guidelines, consider withholding riluzole in patients experiencing fatigue while taking riluzole. C Management of cognitive impairment: insufficient evidence to recommend pharmacologic agents for the management of cognitive or behavioral impairment in patients with ALS. Show 3 more Management of of venous thrombosis: As per ALSSC 2020 guidelines: Initiate anticoagulation as per standard VTE guidelines for the management of VTE in patients with ALS. E Do not administer VTE prophylaxis in nonhospitalized patients with ALS. D As per EFNS 2012 guidelines: Initiate anticoagulant therapy for the treatment of DVT. E Manage risk factors for venous thrombosis. Offer physiotherapy, limb elevation, and compression stockings. E Insufficient evidence to support the prophylactic use of anticoagulants. Therapies with no evidence for benefit: As per EFNS 2012 guidelines, insufficient evidence to support the use of vitamins, testosterone, antioxidants (such as co-enzyme Q-10 and ginkgo biloba), IVIG, cyclosporin, interferons, glatiramer acetate, KDI tripeptide, neurotrophic factors (including brain-derived neurotrophic factor, IGF-1, and mecasermin rinfabate), ceftriaxone, creatine, gabapentin, minocycline, stem cells, or lithium. I As per AAN 2009 guidelines, do not use high-dose vitamin E in the treatment of patients with ALS. D Insufficient evidence to support the use of low-dose vitamin E for the treatment of ALS D Show 2 more Palliative care: As per ALSSC 2020 guidelines, consider providing palliative care in patients with ALS throughout the disease course by ALS clinic staff, palliative care practitioners, and family physicians. E Show 9 more As per EFNS 2012 guidelines, offer input from a palliative care team early in the course of the disease whenever possible. Show 3 more End-of-life care: https://web.pathway.md/diseases/recoWND9TN3ZBmenp 10/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway As per ALSSC 2020 guidelines, refer patients to a physician or nurse practitioner for discussions about medical assistance in dying, abiding by regional guidelines. E Show 3 more As per EFNS 2012 guidelines, initiate discussions on end-of-life decisions when the patient asks or provides an opportunity for discussion on the provision of end of life information and/or interventions. Show 5 more 5. Nonpharmacologic interventions Exercise: consider advising regular moderate-intensity exercise for improved function and quality of life in the early phases of ALS. C Consider offering a personalized exercise program, including strength with submaximal effort for resistance and aerobic training. E Show 2 more Nutritional support: As per ALSSC 2020 guidelines, monitor nutritional status by weight and BMI every 3 months, or as clinically indicated. Consider assessing total daily energy expenditure. B Show 10 more As per EFNS 2012 guidelines, assess bulbar dysfunction and nutritional status (including body weight) at each visit. Recognize that difficulty drinking tap water is frequently the first sign of significant dysphagia. E Show 7 more As per AAN 2009 guidelines, consider performing placement of a percutaneous endoscopic gastrostomy in order to provide enteral nutrition and stabilize body weight in patients with ALS with impaired oral food intake. C 6. Patient education General counseling: discuss treatment options and research opportunities in patients with ALS. E Show 4 more 7. Follow-up and surveillance Indications for referral: refer patients with suspected ALS to an experienced neurologist. E Show 2 more Follow-up: As per ALSSC 2020 guidelines, review medications regularly and consider discontinuing any nonessential medications. Continue symptom management medications. Discontinue primary https://web.pathway.md/diseases/recoWND9TN3ZBmenp 11/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway prevention medications if the duration of effect is longer than the expected survival. Consider discontinuing statins based on the patient's expected survival and cardiovascular risks. E As per EFNS 2012 guidelines: Monitor patients every 2-3 months (more frequently in the months following diagnosis or in the later stages of the disease, and less frequently if the disease is progressing slowly). Maintain regular contact with the patient and relatives between visits. E Ensure to follow the patient by the same neurologist liaising closely with the patient's primary care physician. E References 1. Christen Shoesmith, Agessandro Abrahao, Tim Benstead et al. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ. 2020 Nov 16;192 46 E1453 E1468. Open 2. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis:, Andersen PM, Abrahams S et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis MALS) revised report of an EFNS task force. Eur J Neurol. 2012 Mar;19 3 360 75. Open 3. Paul M Lantos, Jeffrey Rumbaugh, Linda K Bockenstedt et al. Clinical Practice Guidelines by the Infectious Diseases Society of America IDSA , American Academy of Neurology AAN , and American College of Rheumatology ACR 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. Arthritis Care Res Hoboken). 2021 Jan;73 1 1 9. Open 4. Miller RG, Jackson CE, Kasarskis EJ 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 Oct 13;73 15 1218 26. Open 5. Akram Khan, Lindsy Frazer-Green, Reshma Amin et al. Respiratory Management of Patients with Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report. Chest. 2023 Mar 13;S0012 3692 23 00353 7. Open 6. Miller RG, Jackson CE, Kasarskis EJ et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73 15 1227 33. Open 7. Salameh JS, Brown RH Jr, Berry JD. Amyotrophic Lateral Sclerosis: Review. Semin Neurol. 2015 Aug;35 4 469 76. Open 8. Mehta P, Kaye W, Raymond J et al. Prevalence of Amyotrophic Lateral Sclerosis United States, 2015. MMWR Morb Mortal Wkly Rep. 2018 Nov 23;67 46 1285 1289. Open 9. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J Med. 2017 Jul 13;377 2 162 172. Open 10. J M Cedarbaum, N Stambler, E Malta et al. The ALSFRS R a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group Phase III . J Neurol Sci. 1999 Oct 31;169 1 2 13 21. Open https://web.pathway.md/diseases/recoWND9TN3ZBmenp 12/13 6/23/23, 2:35 AM Amyotrophic lateral sclerosis Pathway 11. B R Brooks, R G Miller, M Swash et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1 5 293 9. 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