Progressive speech impairment as the first manifestation of amyotrophic lateral sclerosis: Case report and literature review

Progressive speech impairment as the first manifestation of amyotrophic lateral sclerosis: Case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Progressive speech impairment as the first manifestation of amyotrophic lateral sclerosis: Case report and literature review Jhordan Alexis Paredes Bernales, Henry Flores Navarro, Andre Nelson Sotomayor Serruto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5799121/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease with an incidence of 1.59 per 100,000 people per year. It is characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular dysfunction, and eventual severe disability. This case report presents a 62-year-old male patient from Tarapoto who initially exhibited progressive dysarthria as his sole symptom. Two months later, he developed dysphagia for solids and liquids and weakness in his right lower limb. The diagnosis of ALS was established using the revised El Escorial and Awaji-Shima criteria, supported by electromyography findings indicative of acute denervation and chronic reinnervation in multiple segments, including bulbar and thoracic areas. Complementary studies, such as brain tomography, revealed cortico subcortical frontoparietal atrophy without significant findings suggesting other associated pathologies. The patient’s management included physical and speech therapy over multiple sessions, resulting in mild improvements in dysarthria and dysphagia, allowing greater fluency in speech and better tolerance to liquid intake. However, specific pharmacological therapies for ALS, such as riluzole, edaravone, or mitochondrial dysfunction-targeted combinations, were unavailable, limiting the potential to delay disease progression. During his evolution, the patient developed episodes of bronchitis treated with antitussive and mucolytic therapy, with no significant pulmonary complications. Bulbar phenotype ALS, present in 25–30% of cases, poses a diagnostic challenge due to its variable clinical presentation and inevitable progression. This case highlights the importance of comprehensive, multidisciplinary management, including early interventions to address physical, psychological, and social symptoms, as well as palliative strategies to optimize the quality of life for the patient and their family. Although non-pharmacological therapy achieved partial improvements, early access to approved treatments and specialized resources could have provided greater functional and survival benefits. Neurology Hospital Medicine Neurodegenerative Deglutition Disorders Dysphagia Dysarthria Figures Figure 1 Figure 2 Introduction Amyotrophic Lateral Sclerosis (ALS) is a rare disease with a prevalence of 4.42 per 100,000 people per year and an incidence of 1.59 per 100,000 people per year ( 1 ). However, variations exist across continents, with higher rates observed in Europe and the Americas compared to Africa and Asia. These epidemiological differences are associated with genetic factors ( 1 , 2 ). Additionally, ALS is more common in males and typically occurs within the age range of 70–79 years ( 1 ). ALS is a multisystem neurodegenerative disease that leads to the loss of neuromuscular connections, axonal retraction, and subsequent death of upper motor neurons (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem nuclei, and anterior horn of the spinal cord. As a result, it manifests with a variety of signs and symptoms, although the classic presentation involves progressive muscle weakness, predominantly distal in the limbs ( 3 ). The etiology is complex, hypothesized to be the result of a combination of environmental factors, genetics, and aging, leading to the expression of multiple phenotypes ( 3 ). Diagnosis is based on clinical evaluation and neurological examination. Complementary studies, such as electromyography to assess affected muscles and serological tests, enhance diagnostic accuracy ( 4 ). Therefore, we present the case of a patient with ALS who initially exhibited a single symptom that progressed over time to include other clinical manifestations. The treatment administered and the patient’s response to the interventions are also discussed. Case report A 62-year-old male patient from Tarapoto, with no comorbidities or reported history of pathological or surgical conditions, reported experiencing dysarthria for the past three months. He described “speaking slowly, softly, or stuttering,” but decided not to seek medical attention as it did not interfere with his daily activities or quality of life. However, one month later, he developed dysphagia, describing difficulty consuming both liquids and solids, which prompted him to attend the neurology outpatient clinic. During his evaluation, vital signs were recorded as follows: blood pressure of 138/84 mmHg, heart rate of 77 beats per minute, respiratory rate of 10 breaths per minute, temperature of 36°C, oxygen saturation of 98%, weight of 68 kg, height of 1.69 m, and a body mass index of 23.8, indicating a healthy weight. Neurological examination revealed a lucid patient with bilateral cranial nerve IX and X involvement, monoparesis in the right lower limb, and hyporeflexia (+/++) in the same limb. An electromyography (EMG) was performed on the upper and lower limbs as well as accessory muscles. The examination was conducted while the patient was awake, under satisfactory technical conditions, using surface electrodes, an electrical stimulator, and a sterile 26G monopolar needle. Motor and sensory conduction velocities were assessed bilaterally in the lower limbs and in the right upper limb, including the peroneal motor, proximal peroneal motor, tibial motor, sural sensory, left median motor and sensory, and right ulnar motor and sensory nerves. Sensory and motor potentials in the lower limbs were within normal limits. F-waves showed minimal latencies and appropriate persistence, except in the peroneal nerves, which were inconsistent. The H-reflex was present with normal minimal latency, but the H/M index exceeded 50% (normal value: less than 50%). The EMG evaluated muscles from various segments, including bilateral anterior tibialis, right medial gastrocnemius, left vastus lateralis, bilateral biceps, left brachioradialis, right abductor pollicis brevis, right pronator teres, left first dorsal interosseous, glossus, sternocleidomastoid, T5 right paravertebral, and L2 left paravertebral muscles. Findings suggested acute denervation in all muscles evaluated except the vastus lateralis, with positive waves, fibrillations, and fasciculations in some muscles. Early denervation was noted in the vastus lateralis muscles, and chronic reinnervation was observed in the extremity muscles. These findings indicated denervation across multiple levels and segments, including the bulbar and thoracic regions, consistent with motor neuron disease. The revised El Escorial and Awaji-Shima criteria supported a diagnosis of ALS with a bulbar phenotype (Table 1 ) (Table 2 ). At his next follow-up, the patient reported occasional episodes of mild cramping in the right lower limb, persistent difficulty vocalizing fluently, and consuming both liquids and solids. Weakness in the right lower limb persisted, with muscle strength assessed as 4/5 distally and 3/5 proximally. A non-contrast cranial CT scan revealed pronounced frontoparietal cortico-subcortical atrophy with calcification in the falx cerebri (Fig. 1 ). Consequently, physical and speech therapy was initiated, consisting of 20 sessions, seven times per week, during the first cycle. The patient showed slight improvement in vocalization, though dysphagia to liquids persisted. The patient subsequently developed a productive cough with sputum. A pulmonology consultation diagnosed bronchitis, and the patient received antitussive and mucolytic therapy to alleviate respiratory symptoms. A thoracic CT scan was ordered to rule out other pulmonary pathologies, which showed no significant findings. Subsequently, the patient showed improved swallowing, with no discomfort while consuming liquids or solids, although dysarthria persisted. Physical therapy was reinforced with 10 sessions, three times per week, along with speech therapy of equal duration and frequency during the second cycle. The patient reported slight improvement after completing the sessions and was scheduled for referral to a multidisciplinary center for more complex management. Table 1 Revised El Escorial Criteria. The diagnosis of ALS requires: (A) The presence of: (A:1) Evidence of lower motor neuron (LMN) degeneration through clinical examination, electrophysiological studies, or neuropathological findings, (A:2) Evidence of upper motor neuron (UMN) degeneration through clinical examination, and (A:3) Progressive spread of symptoms or signs within a region or to other regions, as determined by clinical history or examination. B The absence of: (B:1) Electrophysiological or pathological evidence of other pathological processes that could explain the signs of lower and/or upper motor neuron degeneration. (B:2) Neuroimaging evidence of other pathological processes that could account for the observed clinical and electrophysiological findings. Clinical suspicion of ALS Clinically Possible ALS Clinically Probable ALS with Laboratory Support Clinically Probable ALS Clinically Defined ALS ALS may be suspected in many scenarios where the diagnosis cannot be considered sufficiently certain to include the patient in a confirmed category. Consequently, this category is excluded. Signs of dysfunction in both upper motor neurons (UMN) and lower motor neurons (LMN) found together in a single region, or UMN signs alone in two or more regions, or LMN signs found rostral to UMN signs, without sufficient evidence for a definitive ALS diagnosis. Presence of clinical signs of dysfunction in both UMN and LMN in a single region or UMN signs alone in one region, accompanied by LMN signs defined by electromyography criteria in at least two regions, while excluding other causes through neuroimaging and laboratory studies. Presence of UMN and LMN signs in at least two regions, with UMN signs necessarily rostral (above) the LMN signs. Presence of signs of degeneration in both UMN and LMN in the bulbar region and at least two spinal regions, or the presence of UMN and LMN signs in three spinal regions. Table 2 Awaji-Shima criteria Clinically Possible ALS Clinically Probable ALS Clinically Definite ALS Clinical or electrophysiological evidence of either UMN or LMN signs alone in two or more regions, or LMN signs rostral to the UMN signs. Clinical or electrophysiological evidence of both UMN and LMN signs in at least two regions, with some UMN signs rostral to the LMN signs. Clinical or electrophysiological evidence of both UMN and LMN signs in the bulbar region and at least two spinal regions, or UMN and LMN signs in three spinal regions. Discussion This case involves a patient diagnosed with ALS presenting with a bulbar phenotype, which occurs in 25–30% of cases. It is characterized by dysphagia, dysarthria, dysphonia, and, less frequently, weakness of the masseter muscle ( 3 ). ALS involves various molecular mechanisms, including proteostasis failure, mitochondrial dysfunction, oxidative stress, oligodendrocyte dysfunction, cytoskeletal alterations, axonal transport defects, RNA metabolism disruption, nucleocytoplasmic transport deficits, and impaired DNA repair. These mechanisms are grouped into key pathways related to protein quality control and degradation, RNA metabolism, cytoskeletal and axonal transport ( 3 ). Moreover, disease manifestation is multifactorial, with a strong genetic component associated with mutations in the SOD1, FUS, TARDBP, and C9orf72 genes, the latter being the most prevalent ( 5 ). Diagnosing ALS is challenging due to its clinical variability. However, diagnostic criteria such as the revised El Escorial and Awaji-Shima criteria facilitate the identification of signs and symptoms. The Awaji-Shima criteria exhibit higher sensitivity (81.1%) compared to the El Escorial criteria (62.2%) while maintaining equal specificity (95%) ( 6 , 7 ). Managing ALS requires a multidisciplinary approach as the disease impacts the physical, social, and psychological well-being of patients. Comprehensive care is essential to improve adherence to treatment and overall management ( 8 ). Pharmacological therapy includes three drugs approved by the United States Food and Drug Administration (FDA) specifically for ALS treatment ( 8 ). Riluzole, the first medication for ALS management, acts as an antiglutamatergic agent. It inhibits presynaptic glutamate release, blocks protein kinase C, deactivates voltage-gated sodium channels, and moderately inactivates potassium channels. It has been shown to slow muscle function decline, improve survival, and reduce neuronal death, with mild side effects such as asthenia and elevated liver enzymes ( 8 , 9 ) Edaravone, a free radical scavenger with anti-inflammatory properties, moderately delays disease progression ( 9 ). A combination of sodium phenylbutyrate and taurursodiol targets mitochondrial dysfunction, endoplasmic reticulum stress, and cell death ( 10 ). In the presented case, pharmacological therapy was unavailable. Nonetheless, the patient experienced slight improvements in mobility in the right lower limb, enabling reintegration into basic daily activities. Dysphagia and dysarthria improved solely with speech therapy. However, better outcomes could have been achieved with an earlier initiation of multidisciplinary care. The median survival of ALS patients ranges from 2 to 5 years from symptom onset but can vary depending on contributing factors( 11 ) Disease progression is often evaluated using the Revised ALS Functional Rating Scale (ALSFRS-R), where respiratory function is crucial for prognosis. However, ALSFRS-R has limitations as score changes may not accurately reflect disease progression but rather symptomatic management or therapeutic decisions, leading to score increases due to effective clinical interventions despite underlying pathology progression ( 4 , 12 ). Another evaluation tool, the Rasch-Built Overall Disability Scale for ALS (ROADS), provides a more accurate representation of functional changes throughout the disease's progression, encompassing both higher and lower levels of disability ( 12 ). Executive function impairment is a negative prognostic marker and tends to worsen over time( 9 ) Cognitive deficits may develop in later stages, even in patients initially presenting with preserved cognition at diagnosis, and are often associated with the progressive decline in motor functions ( 12 , 13 ). Gradual neuromuscular respiratory failure, secondary to diaphragm weakness, remains the leading cause of morbidity and mortality in ALS patients ( 9 , 12 ). Early palliative care focuses on alleviating symptoms such as pain, fatigue, dyspnea, and sialorrhea, addressing emotional issues related to the loss of independence, communication difficulties, and depression. Caregivers face significant physical, economic, and emotional demands stemming from the patient’s functional decline. Palliative care aims to relieve symptoms, enhance quality of life, establish therapeutic goals, and optimize functional status. Although these interventions can extend survival, they cannot significantly slow the loss of physical autonomy ( 14 ). In this case, the patient’s early clinical presentation did not exhibit severe physical, social, or psychological impact. Nevertheless, the disease's progression is definitive, underscoring the necessity of a multidisciplinary approach. Conclusions Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disease that, despite being rare, significantly impacts patients' quality of life due to its progression and complexity. The presented case illustrates how early-onset bulbar phenotype manifestations can progress to broader neuromuscular involvement, emphasizing the importance of early diagnosis based on clinical criteria and complementary studies such as electromyography. Multidisciplinary management is essential to address the physical, psychological, and social aspects of the disease. Although pharmacological therapy with riluzole, edaravone, and the combination of sodium phenylbutyrate and taurursodiol was not available in this case, physical and speech therapies demonstrated slight improvements in the patient’s quality of life. However, the progression of ALS is inevitable, highlighting the importance of early palliative strategies to manage symptoms, optimize functional status, and support both the patient and their family. Ultimately, this case underscores the need for a comprehensive approach from the outset to maximize the time and quality of life for ALS patients. Declarations Source of funding self-financed Conflict of interest The authors declare no conflict of interest. Ethical Considerations Confidentiality of data: The authors declare that they have followed the protocols of Hospital II-2 Tarapoto on the publication of patient data. Right to privacy and informed consent: The authors declare that they requested informed consent from the patient, which was reviewed and accepted by the ethics committee of Hospital II-2 Tarapoto. References Xu L, Liu T, Liu L, Yao X, Chen L, Fan D et al Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol [Internet]. 2020 Apr 1 [cited 2024 Nov 27];267(4):944–53. Available from: https://link.springer.com/article/10.1007/s00415-019-09652-y Longinetti E, Fang F Epidemiology of amyotrophic lateral sclerosis: An update of recent literature. Curr Opin Neurol [Internet]. 2019 Oct 1 [cited 2024 Nov 27];32(5):771–6. Available from: https://journals.lww.com/co-neurology/fulltext/2019/10000/epidemiology_of_amyotrophic_lateral_sclerosis__an.18.aspx Masrori P, Van Damme P (2020) Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol [Internet]. Oct 1 [cited 2024 Dec 4];27(10):1918–29. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14393 Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ et al (2022) Amyotrophic lateral sclerosis. The Lancet [Internet]. Oct 15 [cited 2024 Nov 27];400(10360):1363–80. Available from: http://www.thelancet.com/article/S0140673622012727/fulltext Zamani A, Thomas E, Wright DK (2024) Sex biology in amyotrophic lateral sclerosis. Ageing Res Rev [Internet]. Mar 1 [cited 2024 Nov 30];95. Available from: https://www.sciencedirect.com/science/article/pii/S1568163724000461?via%3Dihub Costa J, Swash M, De Carvalho M Awaji Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis: A Systematic Review. Arch Neurol [Internet]. 2012 Nov 1 [cited 2025 Jan 3];69(11):1410–6. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/1309686 Brooks BR, Miller RG, Swash M, Munsat TL El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis [Internet]. 2000 [cited 2025 Jan 2];1(5):293–9. Available from: https://www.tandfonline.com/doi/abs/10.1080/146608200300079536 Ilieva H, Vullaganti M, Kwan J (2023) Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis. BMJ [Internet]. Oct 27 [cited 2025 Jan 5];383. Available from: https://www.bmj.com/content/383/bmj-2023-075037 Gupta D, Vagha S, Dhingra H, Shirsath H Advances in Understanding and Treating Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review. Cureus [Internet]. 2023 Nov 12 [cited 2024 Nov 30];15(11). Available from: https://pubmed.ncbi.nlm.nih.gov/38090405/ Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S et al Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. New England Journal of Medicine [Internet]. 2020 Sep 3 [cited 2025 Jan 5];383(10):919–30. Available from: https://www.nejm.org/doi/full/ 10.1056/NEJMoa1916945 Tao QQ, Wu ZY (2017) Amyotrophic Lateral Sclerosis: Precise Diagnosis and Individualized Treatment. Chin Med J (Engl) [Internet]. Oct 5 [cited 2025 Jan 5];130(19):2269. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5634073/ Goutman SA, Hardiman O, Al-Chalabi A, Chió A, Savelieff MG, Kiernan MC et al Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis. Lancet Neurol [Internet]. 2022 May 1 [cited 2025 Jan 2];21(5):480–93. Available from: http://www.thelancet.com/article/S1474442221004658/fulltext Roche JC, Rojas-Garcia R, Scott KM, Scotton W, Ellis CE, Burman R et al A proposed staging system for amyotrophic lateral sclerosis. Brain [Internet]. 2012 Mar 1 [cited 2025 Jan 5];135(3):847–52. Available from: https://dx.doi.org/10.1093/brain/awr351 Mercadante S, Al-Husinat L Palliative Care in Amyotrophic Lateral Sclerosis. J Pain Symptom Manage [Internet]. 2023 Oct 1 [cited 2025 Jan 5];66(4):e485–99. Available from: http://www.jpsmjournal.com/article/S0885392423005742/fulltext Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5799121","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":400163435,"identity":"af957abc-1676-4d63-b70f-925025ce9736","order_by":0,"name":"Jhordan Alexis Paredes Bernales","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-4098-2948","institution":"UNSM","correspondingAuthor":true,"prefix":"","firstName":"Jhordan","middleName":"Alexis Paredes","lastName":"Bernales","suffix":""},{"id":400163436,"identity":"a67ac307-7df6-47ec-b610-02da3607e1ec","order_by":1,"name":"Henry Flores Navarro","email":"","orcid":"https://orcid.org/0000-0002-9857-8833","institution":"Hospital II-2 Tarapoto","correspondingAuthor":false,"prefix":"","firstName":"Henry","middleName":"Flores","lastName":"Navarro","suffix":""},{"id":400163437,"identity":"f02e2b58-393f-4a77-a319-ebb7a7e41762","order_by":2,"name":"Andre Nelson Sotomayor Serruto","email":"","orcid":"https://orcid.org/0009-0003-4750-1793","institution":"Hospital II-2 Tarapoto","correspondingAuthor":false,"prefix":"","firstName":"Andre","middleName":"Nelson Sotomayor","lastName":"Serruto","suffix":""}],"badges":[],"createdAt":"2025-01-09 21:03:51","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5799121/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5799121/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73520245,"identity":"7b159050-8662-4e85-8e88-1c6298f0abed","added_by":"auto","created_at":"2025-01-10 18:13:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":279580,"visible":true,"origin":"","legend":"\u003cp\u003eNon-contrast CT scan. (a) Coronal view: Enlargement of the lateral ventricles, increased definition of cortical sulci, and hyper density corresponding to calcification in the falx cerebri. (b) Axial view: Enlargement of the interhemispheric fissure and anteroposterior extension of falx cerebri calcification. (c) Sagittal view: Apical calcification, increased depth of the interhemispheric fissure, and anteroposterior enlargement of the lateral ventricles.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5799121/v1/388630b274263abafabad633.png"},{"id":73520243,"identity":"f1801bed-4041-42ff-9b3b-a64be066f6b2","added_by":"auto","created_at":"2025-01-10 18:13:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17774,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5799121/v1/b2b16b0b99d1e0132ccc4119.png"},{"id":73520432,"identity":"9e073cdc-e486-4cea-a1b5-fd5508e1e16c","added_by":"auto","created_at":"2025-01-10 18:21:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":747353,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5799121/v1/8ef36d74-c9d8-409d-9e6e-45f797e4218f.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eProgressive speech impairment as the first manifestation of amyotrophic lateral sclerosis: Case report and literature review\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAmyotrophic Lateral Sclerosis (ALS) is a rare disease with a prevalence of 4.42 per 100,000 people per year and an incidence of 1.59 per 100,000 people per year (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, variations exist across continents, with higher rates observed in Europe and the Americas compared to Africa and Asia. These epidemiological differences are associated with genetic factors (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Additionally, ALS is more common in males and typically occurs within the age range of 70\u0026ndash;79 years (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eALS is a multisystem neurodegenerative disease that leads to the loss of neuromuscular connections, axonal retraction, and subsequent death of upper motor neurons (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem nuclei, and anterior horn of the spinal cord. As a result, it manifests with a variety of signs and symptoms, although the classic presentation involves progressive muscle weakness, predominantly distal in the limbs (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe etiology is complex, hypothesized to be the result of a combination of environmental factors, genetics, and aging, leading to the expression of multiple phenotypes (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Diagnosis is based on clinical evaluation and neurological examination. Complementary studies, such as electromyography to assess affected muscles and serological tests, enhance diagnostic accuracy (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, we present the case of a patient with ALS who initially exhibited a single symptom that progressed over time to include other clinical manifestations. The treatment administered and the patient\u0026rsquo;s response to the interventions are also discussed.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 62-year-old male patient from Tarapoto, with no comorbidities or reported history of pathological or surgical conditions, reported experiencing dysarthria for the past three months. He described \u0026ldquo;speaking slowly, softly, or stuttering,\u0026rdquo; but decided not to seek medical attention as it did not interfere with his daily activities or quality of life. However, one month later, he developed dysphagia, describing difficulty consuming both liquids and solids, which prompted him to attend the neurology outpatient clinic. During his evaluation, vital signs were recorded as follows: blood pressure of 138/84 mmHg, heart rate of 77 beats per minute, respiratory rate of 10 breaths per minute, temperature of 36\u0026deg;C, oxygen saturation of 98%, weight of 68 kg, height of 1.69 m, and a body mass index of 23.8, indicating a healthy weight. Neurological examination revealed a lucid patient with bilateral cranial nerve IX and X involvement, monoparesis in the right lower limb, and hyporeflexia (+/++) in the same limb. An electromyography (EMG) was performed on the upper and lower limbs as well as accessory muscles. The examination was conducted while the patient was awake, under satisfactory technical conditions, using surface electrodes, an electrical stimulator, and a sterile 26G monopolar needle. Motor and sensory conduction velocities were assessed bilaterally in the lower limbs and in the right upper limb, including the peroneal motor, proximal peroneal motor, tibial motor, sural sensory, left median motor and sensory, and right ulnar motor and sensory nerves. Sensory and motor potentials in the lower limbs were within normal limits. F-waves showed minimal latencies and appropriate persistence, except in the peroneal nerves, which were inconsistent. The H-reflex was present with normal minimal latency, but the H/M index exceeded 50% (normal value: less than 50%). The EMG evaluated muscles from various segments, including bilateral anterior tibialis, right medial gastrocnemius, left vastus lateralis, bilateral biceps, left brachioradialis, right abductor pollicis brevis, right pronator teres, left first dorsal interosseous, glossus, sternocleidomastoid, T5 right paravertebral, and L2 left paravertebral muscles. Findings suggested acute denervation in all muscles evaluated except the vastus lateralis, with positive waves, fibrillations, and fasciculations in some muscles. Early denervation was noted in the vastus lateralis muscles, and chronic reinnervation was observed in the extremity muscles. These findings indicated denervation across multiple levels and segments, including the bulbar and thoracic regions, consistent with motor neuron disease. The revised El Escorial and Awaji-Shima criteria supported a diagnosis of ALS with a bulbar phenotype (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt his next follow-up, the patient reported occasional episodes of mild cramping in the right lower limb, persistent difficulty vocalizing fluently, and consuming both liquids and solids. Weakness in the right lower limb persisted, with muscle strength assessed as 4/5 distally and 3/5 proximally. A non-contrast cranial CT scan revealed pronounced frontoparietal cortico-subcortical atrophy with calcification in the falx cerebri (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Consequently, physical and speech therapy was initiated, consisting of 20 sessions, seven times per week, during the first cycle. The patient showed slight improvement in vocalization, though dysphagia to liquids persisted.\u003c/p\u003e \u003cp\u003eThe patient subsequently developed a productive cough with sputum. A pulmonology consultation diagnosed bronchitis, and the patient received antitussive and mucolytic therapy to alleviate respiratory symptoms. A thoracic CT scan was ordered to rule out other pulmonary pathologies, which showed no significant findings.\u003c/p\u003e \u003cp\u003eSubsequently, the patient showed improved swallowing, with no discomfort while consuming liquids or solids, although dysarthria persisted. Physical therapy was reinforced with 10 sessions, three times per week, along with speech therapy of equal duration and frequency during the second cycle. The patient reported slight improvement after completing the sessions and was scheduled for referral to a multidisciplinary center for more complex management.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRevised El Escorial Criteria.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eThe diagnosis of ALS requires:\u003c/p\u003e \u003cp\u003e(A) The presence of:\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e(A:1) Evidence of lower motor neuron (LMN) degeneration through clinical examination, electrophysiological studies, or neuropathological findings,\u003c/p\u003e \u003cp\u003e(A:2) Evidence of upper motor neuron (UMN) degeneration through clinical examination, and\u003c/p\u003e \u003cp\u003e(A:3) Progressive spread of symptoms or signs within a region or to other regions, as determined by clinical history or examination.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eB The absence of:\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e(B:1) Electrophysiological or pathological evidence of other pathological processes that could explain the signs of lower and/or upper motor neuron degeneration.\u003c/p\u003e \u003cp\u003e(B:2) Neuroimaging evidence of other pathological processes that could account for the observed clinical and electrophysiological findings.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical suspicion of ALS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClinically Possible ALS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinically Probable ALS with Laboratory Support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClinically Probable ALS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClinically Defined ALS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALS may be suspected in many scenarios where the diagnosis cannot be considered sufficiently certain to include the patient in a confirmed category. Consequently, this category is excluded.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSigns of dysfunction in both upper motor neurons (UMN) and lower motor neurons (LMN) found together in a single region, or UMN signs alone in two or more regions, or LMN signs found rostral to UMN signs, without sufficient evidence for a definitive ALS diagnosis.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresence of clinical signs of dysfunction in both UMN and LMN in a single region or UMN signs alone in one region, accompanied by LMN signs defined by electromyography criteria in at least two regions, while excluding other causes through neuroimaging and laboratory studies.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePresence of UMN and LMN signs in at least two regions, with UMN signs necessarily rostral (above) the LMN signs.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePresence of signs of degeneration in both UMN and LMN in the bulbar region and at least two spinal regions, or the presence of UMN and LMN signs in three spinal regions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAwaji-Shima criteria\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinically Possible ALS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClinically Probable ALS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinically Definite ALS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical or electrophysiological evidence of either UMN or LMN signs alone in two or more regions, or LMN signs rostral to the UMN signs.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClinical or electrophysiological evidence of both UMN and LMN signs in at least two regions, with some UMN signs rostral to the LMN signs.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical or electrophysiological evidence of both UMN and LMN signs in the bulbar region and at least two spinal regions, or UMN and LMN signs in three spinal regions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case involves a patient diagnosed with ALS presenting with a bulbar phenotype, which occurs in 25\u0026ndash;30% of cases. It is characterized by dysphagia, dysarthria, dysphonia, and, less frequently, weakness of the masseter muscle (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). ALS involves various molecular mechanisms, including proteostasis failure, mitochondrial dysfunction, oxidative stress, oligodendrocyte dysfunction, cytoskeletal alterations, axonal transport defects, RNA metabolism disruption, nucleocytoplasmic transport deficits, and impaired DNA repair. These mechanisms are grouped into key pathways related to protein quality control and degradation, RNA metabolism, cytoskeletal and axonal transport (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Moreover, disease manifestation is multifactorial, with a strong genetic component associated with mutations in the SOD1, FUS, TARDBP, and C9orf72 genes, the latter being the most prevalent (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Diagnosing ALS is challenging due to its clinical variability. However, diagnostic criteria such as the revised El Escorial and Awaji-Shima criteria facilitate the identification of signs and symptoms. The Awaji-Shima criteria exhibit higher sensitivity (81.1%) compared to the El Escorial criteria (62.2%) while maintaining equal specificity (95%) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eManaging ALS requires a multidisciplinary approach as the disease impacts the physical, social, and psychological well-being of patients. Comprehensive care is essential to improve adherence to treatment and overall management (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Pharmacological therapy includes three drugs approved by the United States Food and Drug Administration (FDA) specifically for ALS treatment (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Riluzole, the first medication for ALS management, acts as an antiglutamatergic agent. It inhibits presynaptic glutamate release, blocks protein kinase C, deactivates voltage-gated sodium channels, and moderately inactivates potassium channels. It has been shown to slow muscle function decline, improve survival, and reduce neuronal death, with mild side effects such as asthenia and elevated liver enzymes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Edaravone, a free radical scavenger with anti-inflammatory properties, moderately delays disease progression (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). A combination of sodium phenylbutyrate and taurursodiol targets mitochondrial dysfunction, endoplasmic reticulum stress, and cell death (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In the presented case, pharmacological therapy was unavailable. Nonetheless, the patient experienced slight improvements in mobility in the right lower limb, enabling reintegration into basic daily activities. Dysphagia and dysarthria improved solely with speech therapy. However, better outcomes could have been achieved with an earlier initiation of multidisciplinary care.\u003c/p\u003e \u003cp\u003eThe median survival of ALS patients ranges from 2 to 5 years from symptom onset but can vary depending on contributing factors(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Disease progression is often evaluated using the Revised ALS Functional Rating Scale (ALSFRS-R), where respiratory function is crucial for prognosis. However, ALSFRS-R has limitations as score changes may not accurately reflect disease progression but rather symptomatic management or therapeutic decisions, leading to score increases due to effective clinical interventions despite underlying pathology progression (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Another evaluation tool, the Rasch-Built Overall Disability Scale for ALS (ROADS), provides a more accurate representation of functional changes throughout the disease's progression, encompassing both higher and lower levels of disability (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Executive function impairment is a negative prognostic marker and tends to worsen over time(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Cognitive deficits may develop in later stages, even in patients initially presenting with preserved cognition at diagnosis, and are often associated with the progressive decline in motor functions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Gradual neuromuscular respiratory failure, secondary to diaphragm weakness, remains the leading cause of morbidity and mortality in ALS patients (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Early palliative care focuses on alleviating symptoms such as pain, fatigue, dyspnea, and sialorrhea, addressing emotional issues related to the loss of independence, communication difficulties, and depression. Caregivers face significant physical, economic, and emotional demands stemming from the patient\u0026rsquo;s functional decline. Palliative care aims to relieve symptoms, enhance quality of life, establish therapeutic goals, and optimize functional status. Although these interventions can extend survival, they cannot significantly slow the loss of physical autonomy (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In this case, the patient\u0026rsquo;s early clinical presentation did not exhibit severe physical, social, or psychological impact. Nevertheless, the disease's progression is definitive, underscoring the necessity of a multidisciplinary approach.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAmyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disease that, despite being rare, significantly impacts patients' quality of life due to its progression and complexity. The presented case illustrates how early-onset bulbar phenotype manifestations can progress to broader neuromuscular involvement, emphasizing the importance of early diagnosis based on clinical criteria and complementary studies such as electromyography.\u003c/p\u003e \u003cp\u003eMultidisciplinary management is essential to address the physical, psychological, and social aspects of the disease. Although pharmacological therapy with riluzole, edaravone, and the combination of sodium phenylbutyrate and taurursodiol was not available in this case, physical and speech therapies demonstrated slight improvements in the patient\u0026rsquo;s quality of life.\u003c/p\u003e \u003cp\u003eHowever, the progression of ALS is inevitable, highlighting the importance of early palliative strategies to manage symptoms, optimize functional status, and support both the patient and their family. Ultimately, this case underscores the need for a comprehensive approach from the outset to maximize the time and quality of life for ALS patients.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSource of funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eself-financed\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConfidentiality of data: The authors declare that they have followed the protocols of Hospital II-2 Tarapoto on the publication of patient data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRight to privacy and informed consent: The authors declare that they requested informed consent from the patient, which was reviewed and accepted by the ethics committee of Hospital II-2 Tarapoto.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXu L, Liu T, Liu L, Yao X, Chen L, Fan D et al Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.jpsmjournal.com/article/S0885392423005742/fulltext\u003c/span\u003e\u003cspan address=\"http://www.jpsmjournal.com/article/S0885392423005742/fulltext\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"National University of San Martin","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neurodegenerative, Deglutition Disorders, Dysphagia, Dysarthria","lastPublishedDoi":"10.21203/rs.3.rs-5799121/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5799121/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAmyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease with an incidence of 1.59 per 100,000 people per year. It is characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular dysfunction, and eventual severe disability. This case report presents a 62-year-old male patient from Tarapoto who initially exhibited progressive dysarthria as his sole symptom. Two months later, he developed dysphagia for solids and liquids and weakness in his right lower limb.\u003c/p\u003e \u003cp\u003eThe diagnosis of ALS was established using the revised El Escorial and Awaji-Shima criteria, supported by electromyography findings indicative of acute denervation and chronic reinnervation in multiple segments, including bulbar and thoracic areas. Complementary studies, such as brain tomography, revealed cortico subcortical frontoparietal atrophy without significant findings suggesting other associated pathologies.\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s management included physical and speech therapy over multiple sessions, resulting in mild improvements in dysarthria and dysphagia, allowing greater fluency in speech and better tolerance to liquid intake. However, specific pharmacological therapies for ALS, such as riluzole, edaravone, or mitochondrial dysfunction-targeted combinations, were unavailable, limiting the potential to delay disease progression. During his evolution, the patient developed episodes of bronchitis treated with antitussive and mucolytic therapy, with no significant pulmonary complications.\u003c/p\u003e \u003cp\u003eBulbar phenotype ALS, present in 25\u0026ndash;30% of cases, poses a diagnostic challenge due to its variable clinical presentation and inevitable progression. This case highlights the importance of comprehensive, multidisciplinary management, including early interventions to address physical, psychological, and social symptoms, as well as palliative strategies to optimize the quality of life for the patient and their family. Although non-pharmacological therapy achieved partial improvements, early access to approved treatments and specialized resources could have provided greater functional and survival benefits.\u003c/p\u003e","manuscriptTitle":"Progressive speech impairment as the first manifestation of amyotrophic lateral sclerosis: Case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-10 18:12:57","doi":"10.21203/rs.3.rs-5799121/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2276f96f-b32b-44c4-b1ce-e0c2310a256c","owner":[],"postedDate":"January 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42649436,"name":"Neurology"},{"id":42649437,"name":"Hospital Medicine"}],"tags":[],"updatedAt":"2025-01-10T18:12:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-10 18:12:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5799121","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5799121","identity":"rs-5799121","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}