Between Hope and Acceptance: A Case Report of Als and Realities of Palliative Care in Indonesia

Between Hope and Acceptance: A Case Report of Als and Realities of Palliative Care in Indonesia | 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 Between Hope and Acceptance: A Case Report of Als and Realities of Palliative Care in Indonesia Arya Taksya Bagaskara, Kadex Reisya Sita Damayanti, Gilbert Christhew Gunawan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7783546/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Introduction Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease involving upper and lower motor neurons. However, the scarcity of However, the scarcity of pharmacotherapy choices pose significant challenges in managing ALS. This study aims to highlight the realities of ALS management in Indonesia. Case Report A 39-year-old woman presented with dyspnoea and limb weakness in January 2024, which progressed to tetraparesis by July 2025. Her vital signs included a blood pressure of 102/74 mmHg, heart rate of 75 bpm, respiratory rate of 27x/min, temperature of 36°C, and oxygen saturation of 93% (room air). Neurological examination revealed tetraparesis (333/333; 111/111), with bilateral thenar-hypothenar atrophy. Physiological reflexes were diminished, and pathological reflexes were positive. The patient was admitted in early July with similar symptoms. Special examinations via lumbar puncture, magnetic resonance imaging (MRI), and spine CT scans revealed normal results. TTR-amyloidosis antibody, ANA, and anti-TPO test results were negative. Sural nerve biopsy indicated neuropathy. Electromyography revealed denervation from the cervical to lumbosacral regions, leading to a diagnosis of definite ALS (El Escorial criteria, King's grade 3). The ASLFRS-R score was 20. The patient received Riluzole 2x50 mg (from Germany) along with psychological support, physiotherapy, home care, and palliative treatment. Discussion and Conclusion This case highlights the limited access to diagnostic tests and management for ALS in Indonesia. Edaravone and riluzole are the only available symptomatic treatments in Indonesia; unfortunately, their distribution are limited. Palliative and supportive care are currently the only options available for ALS patients in Indonesia. Uncertainty regarding the outcome affects the patient's quality of life. ALS ALS Palliative Care ALS Treatment Case Report Quality of Life Figures Figure 1 Figure 2 Introduction Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease , is a neurodegenerative disease characterized by progressive muscle weakness that is often sporadic in nature and affects upper (UMNs) and lower motor neurons (LMNs). ( 1 ) Amyotrophy refers to muscle fiber atrophy causing weakness and fasciculations, whereas lateral sclerosis refers to atrophy of the anterior and lateral corticospinal tracts due to degeneration and gliosis. Although the exact cause is not yet understood, several theories suggest a link to genetic mutations, glutamate imbalance, neuroinflammation, and mitochondrial dysfunction. ( 3 ) The main cause of mortality is respiratory failure, which occurs approximately 3–5 years after onset. In addition to motor weakness, some patients also experience cognitive or behavioral changes, including frontotemporal dementia. ( 4 ) The prevalence of ALS is reported to be 6/100,000 people, with a peak incidence in people over 50 years of age. To date, few cases of ALS have been reported in Indonesia. ( 1 ) Studies have shown that the incidence rate of ALS will increase by 69%, from 222,801 in 2015 to 376,000 in 2040. The Global Burden of Disease states that there was a 4.5% increase to 330,918 cases from 1990–2016 in America. ( 5 ) ALS is a fatal disease for which no curative treatment has yet been identified. The management of ALS aims to prevent progression and optimize the quality of life of patients. ( 6 ) Riluzole, edaravone, and sodium pheynulbutirate have been approved by the United States Food and Drug Administration (US-FDA) as drugs to improve the survival rate of ALS patients. Oral riluzole was the first preparation approved by the FDA. Riluzole works by reducing glutamate excitotoxicity. ( 7 ) Edaravone is an antioxidant that suppresses oxidative stress. Edaravone has been available in Indonesia since 2020, but its distribution is still limited. ( 6 )( 8 ) A 24-week edaravone therapy regimen was found to reduce the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score by 33%, but subsequent studies have not reported significant outcomes. ( 4 ) The limited options for pharmacological therapy for ALS are one factor contributing to the poor prognosis of patients according to ALSFRS-R scores. This case report aims to describe the challenges associated with the ALS treatment gap faced in clinical practice in Indonesia. Case Report A 39-year-old woman was brought to the Emergency Department (ED) on July 26, 2025, complaining of shortness of breath after choking. The patient had previously experienced weakness in both legs since November 2023, starting with the left leg, followed by the right leg (Fig. 1 ). The patient became bedridden because of these complaints. In January 2024, the weakness in her legs worsened, and since May 2025, the patient has been unable to move both legs, with only slight movement remaining in the tips of her right toes. The weakness then spread to both arms, which began in May 2025. The patient also complained of shortness of breath, which had been felt since February 2025 and worsened, leading to a visit to the emergency department on 5 July 2025. The patient was diagnosed with ALS while working in Germany, with treatment consisting of Riluzole 2×50 mg. The patient had a history of hypothyroidism and was treated with L-thyroxine 2×100 mcg. There were no complaints of visual disturbances. Vital sign examination revealed tachypnea (29 breaths per minute), a blood pressure of 132/90 mmHg, a heart rate of 91 beats per minute, a temperature of 36°C, and an oxygen saturation of 93% ( room air ). Neurological examination of the extremities revealed tetraparesis and muscle strength 333/333; 111/111, with bilateral atrophy of the thenar and hypothenar muscles (Fig. 2). Physiological reflexes were decreased, but pathological Hoffman–Tromner reflexes were present (+/+). The patient then underwent a complete blood count, electrolyte panel, and thyroid panel (Table 1 ). A chest X-ray revealed signs of right hemidiaphragmatic paralysis. The initial thyroid panel results indicated hypothyroidism, but this is now controlled (Table 1 ). Figure 2 . Bilateral atrophy of the thenar and hypothenar muscles Table 1 Patient Laboratory Test Results Examination 5/7/25 26/7/25 Hb (g/dL) 12.4 12.4 Hematocrit (%) 35.8 35.9 Red blood cells (10⁶/µL) 4.47 4.39 Platelets ( 10³ /µL) 376 447 White blood cells (10 ³ /µL) 8.33 11.54 (H) Basophils (%) 0.7 1.1 Eosinophils (%) 12.1 (H) 10.2 (H) Neutrophils (%) 44.6 (L) 47.5 (L) Lymphocytes (%) 34.1 34.8 Monocytes (%) 8.5 6.4 Sodium (mEq/L) 134 137.1 Potassium (mEq/L) 3.7 4.06 FT4 (pmol/L) 40.53 (L) 19.05 TSH 4.68 (Hour) 0.834 Before undergoing therapy in Indonesia, the patient had already undergone supporting examinations in Germany. The examinations conducted were as follows: lumbar puncture with normal results; sural nerve biopsy showing neuropathy; and autoimmune and infection panels, including Transthyretin Amyloidosis, Antinuclear Antibody , C1q-ak, Anti-Thyroid Peroxidase Antibody, and Anti-Cytomegalovirus IgG , all of which were negative. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the spine at the German hospital revealed normal results. The diagnosis of ALS was confirmed via the El Escorial Classification and Awaji criteria. The electromyography (EMG) results revealed denervation of the cervical, thoracic, and lumbar regions. The patient's El Escorial score indicated definite ALS with an ASLFRS-R score of 20 (20–25% chance of survival at 9 months). On the basis of the clinical findings, the patient was categorized as King's Stage 3, characterized by tetraparesis and dyspnea due to bulbar palsy with muscle atrophy. The patient then underwent spirometry, which revealed restrictive lung disease characterized by a forced vital capacity (FVC) of 38%. The patient was recommended to receive oxygen therapy via continuous positive airway pressure (CPAP). Two days after hospitalization, the patient was discharged with tetraparesis, and her dyspnea improved. Riluzole therapy was continued without any additional therapy. During psychological counseling sessions, the patient admitted to feeling afraid of the journey toward death but had accepted their condition and was prepared to face the end. The patient was discharged with supportive and palliative care management. Discussion Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by gradual muscle paresis leading to respiratory distress . This disease causes voluntary motor degeneration, starting from the motor neurons in the motor cortex to the neuromuscular junction. ( 9 ) The pathogenesis of ALS is not fully understood and is multifactorial. The main pathomechanism of ALS involves disruption of protein homeostasis, particularly the intracellular protein degradation mechanism. There are two main pathways responsible for protein degradation, namely, the ubiquitin‒proteasome system (UPS) and the autophagy mechanism. ( 10 ) The UPS pathway functions to destroy proteins that have been identified for elimination. 11) In addition, the autophagy pathway plays a role in breaking down large protein aggregates that cannot be handled by the UPS. Dysfunction of these two systems leads to the accumulation of abnormal proteins such as TDP-43, which triggers cellular stress, apoptosis, and the formation of cytoplasmic inclusions known as Bunina bodies. ( 12 ) Epidemiologically, approximately 85–90% of ALS cases are sporadic, whereas the remaining 10% are autosomal dominant. ( 13 ) One of the most widely studied genetic mutations is the superoxide dismutase 1 (SOD1) gene on chromosome 21. This gene functions to convert superoxide free radicals into oxygen and hydrogen peroxide, thereby protecting cells from oxidative stress. SOD1 mutations can trigger the unfolded protein response , endoplasmic reticulum stress, and motor neuron death through the activation of autophagy and the apoptosis pathway. ( 14 , 15 ) Five main interrelated mechanisms are involved in the pathophysiology of ALS: ( 1 ) neuronal protein homeostasis disorders; ( 2 ) RNA metabolism dysfunction; ( 3 ) glutamate excitotoxicity; ( 4 ) mitochondrial dysfunction; and ( 5 ) the inhibition of intraneuronal axoplasmic transport. These processes lead to the destruction of motor neurons, both Betz cells in the motor cortex and anterior horn cells in the spinal cord, through retrograde axonal degeneration. This process causes the gradual manifestation of paralysis in ALS patients. The lack of epidemiological data poses a challenge in identifying the burden of disease from ALS. The cost of illness (COI) for ALS patients in Germany reaches €78,256 per person per year. Among these costs, 35.9% are direct medical costs, 49.1% are direct nonmedical costs, and 15% are indirect costs. ( 4 , 16 ) The economic burden of ALS stems not only from medical care costs but also from the need for nonmedical support and loss of productivity due to the disease. Data on the burden of ALS in Indonesia are still very limited. There are only two follow-up studies related to ALS in Papua. In 2012, there were 46 cases of ALS and/or parkinsonism, with a population range of 20,900 (2001–2012). A previous study reported 57 clinically confirmed cases of ALS from 1974–1981. ( 17 ) The prevalence rate of ALS in this study ranged from 27–240/100,000 individuals. The incidence and prevalence of ALS in this study were found to be higher than the global incidence (2/100,000) and prevalence (6/100,000) figures in 2013. ( 18 ) The highest incidence of ALS was found after the age of 50; therefore, previous studies assumed that the prevalence of ALS in Indonesia was only 2,500 individuals. This figure was obtained only by assuming that 15% of the Indonesian population was over 50 years of age in 2015. ( 2 ) These findings indicate that there is underreporting and underdiagnosis of ALS cases in Indonesia, leading to an iceberg phenomenon in the actual incidence and prevalence rates of ALS in Indonesia. This causes major pitfalls in the burden of disease from ALS cases. To date, there is no definitive treatment for ALS, and treatment is only symptomatic. According to the American Academy of Neurology, 2009 , the first-line pharmacological treatment for ALS is riluzole and edaravone, and the second-line treatment is sodium phenylbutyrate/taurursodiol, along with other experimental agents. ( 4 ) The current pharmacological agent and its properties comparison for ALS is presented in (Table 2 ). Table 2 Comparison of therapies for ALS Riluzole Edaravone Sodium Phenylbutyrate/Taurursodiol Mechanism of Action Glutamate antagonist (antitoxicity) Antioxidant (targets oxidative stress) Mitochondrial and endoplasmic reticulum protection Impact on ALS progression Slightly delays ALS progression; extends survival by 2–3 months Slightly delays ALS progression; extends survival by 6 months ( 19 ) Slight improvement in function and reduction in progression Dosage 2x50 mg/day orally (maximum 100 mg/day) ( 20 ) Intravenous dose: 60 mg/day (maximum dose not yet determined) Oral suspension dosage: 105 mg/5 ml daily ( 20 ) 1 dose of medication (3 g Sodium Phenylbutyrate + 1 g Taurursodiol) once daily for 3 weeks, then twice daily Duration of use Lifetime For 14 days, followed by 14 days without medication, and the cycle is repeated for life Initial dose: 1 dose of medication daily for 21 days Maintenance dose: 1 dose of medication twice daily ( 20 ) Side effects Asthenia, nausea, impaired respiratory function, gastrointestinal symptoms, and hepatotoxicity Hypoesthesia, gait imbalance , headache, and skin conditions Gastrointestinal symptoms (diarrhea, nausea, hypersalivation, and abdominal cramps ) ( 21 ) Safety Adverse events occurred in 5% of patients with the following symptom composition: asthenia a (19%), nausea (16%), decreased respiratory function (10%), hypertension (5%), and abdominal pain (5%). Serious events had a prevalence of 11.4% of all adverse events. ( 20 ) Hypoesthesia occurred in 38% of cases, and pancreatitis occurred in 1 out of 100–1,000 patients with and edaravone consumption. No deaths or serious events were reported. ( 20 ) Unexpected events included gastrointestinal disorders (67%), musculoskeletal disorders (43%),, and other systemic disorders (> 5%). For serious events, the prevalence was 12%, with the prevalence of treatment-related deaths still unknown. ( 21 ) ALSFRS-R score No significant changes were observed at 6 or 12 months of treatment. ( 22 ) Rate of change in ALSFRS-R score: -5.01 to -7.5 points over 24 weeks. ( 19 ) Rate of change in ALSFRS-R score: -1.24 points/month Compared with the placebo, the administration of 100 mg of Riluzole increased the probability of 1-year tracheostomy-free survival by 9%. ( 7 ) Riluzole significantly prolonged the survival period by 2 months to 22 months compared with patients who did not receive Riluzole, which was 20 months. ( 4 )( 15 ) The progression of bulbar function decline after 12 months of 100 mg Riluzole was found to be 2.06 times slower than that of the placebo. The degradation of extremity function was 3.94 times slower after the administration of 100 mg of Riluzole for 12 months. ( 23 ) Compared with edaravone, riluzole was found to prolong life expectancy in early-stage ALS patients, whereas edaravone is only a symptomatic therapy. ( 24 ) In vitro studies have shown that the combination of Riluzole and sodium phenylbutyrate results in lower SOD1 concentrations in the spinal cord, intestine and cerebral cortex than does monotherapy. ( 25 ) Further pharmacovigilance studies are not yet available. The limitations of supportive therapy make palliative therapy an important part of comprehensive ALS management. Although physical, occupational, and speech therapy can help maintain independence, nutritional and ventilation therapy aims to maintain patients’ physical well-being. ( 4 ) The progression of ALS causes respiratory and bulbar muscle paralysis, which is important for maintaining airway patency. ( 4 , 26 ) The accumulation of CO₂ due to respiratory muscle weakness triggers hypercapnia and organ hypoperfusion, including in the central nervous system, which disrupts lymphatic function, such as toxin clearance and sclerosis, and exacerbates cerebral vascular damage. These disorders further exacerbate the progression and clinical outcomes of ALS. ( 27 ) Noninvasive ventilation (NIV) is one of the main components of symptomatic management in individuals with ALS to improve survival and quality of life. ( 28 ) The European Federation of Neurological Societies ( EFNS) recommends initiating NIV in patients with respiratory symptoms or if FVC < 80%, SNIP 45 mmHg, or nocturnal desaturation is observed. Other studies have shown that earlier NIV (FVC > 80%) results in a slower decline in FVC than does placebo. ( 29 ) Psychological aspects are crucial in palliative ALS care, as depression and anxiety are common. ( 30 ) Psychotherapy and pharmacotherapy interventions such as fast-acting anxiolytics, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs) can reduce depression and anxiety, as supported by palliative care studies. ( 31 ) Physical and occupational therapy support motor function adaptation, although evidence of their effectiveness is still limited. ( 30 , 32 ) There are eight predictors of transition to palliative care, including young onset and bulbar palsy, as found in this case. Other predictors are a definitive diagnosis of ALS, delayed diagnosis, decreased forced vital capacity , rate of progression, coexisting frontotemporal dementia, and the presence of C9 or F72 repeat expansions. ( 33 ) ALS management in Indonesia requires a comprehensive reform strategy to formulate a standardized ALS clinical pathway . The algorithm is aimed at early identification with the support of EMG and MRI, as well as clinical classification on the basis of the Gold Coast criteria and El Escorial diagnostic criteria. The formulation of this pathway can be based on Kings staging, the ASLSFRS-R, and the Norris scale. Supporting examinations such as genetic testing, neuron/myocyte biopsy, and autoimmune panels are still limited. Currently, only edaravone is available, whereas riluzole and sodium phenylbutyrate-taurursodiol are not yet officially available, requiring independent importation, causing delays in therapy and worsening clinical outcomes, including the progression of onset. It is hoped that through this case report, pharmacological preparations such as riluzole, sodium phenylbutyrate , and taurursodiol will become available in Indonesia. Delays in the administration of pharmacological management can significantly reduce the survival rate of ALS patients. In addition, early assessment of accompanying symptoms such as dyspnea due to bulbar palsy and the need for medical aids such as CPAP should be standardized in all secondary facilities. The delayed diagnosis of ALS patients, especially those with bulbar onset , is associated with a poorer quality of life , a greater need for NIV and percutaneous gastrotomy , and a lower survival rate . ( 34 ) Conclusion This case represents a concrete example of the challenges of managing ALS in Indonesia. Limited access to gold standard diagnostic modalities and pharmacological and nonpharmacological management remains one of the predictors of clinical outcomes for ALS patients in Indonesia. This case report also highlights palliative therapy options that can improve the quality of life of ALS patients. Declarations Ethics approval: Ethical approval was not required for this case report, as it does not involve research on human subjects beyond standard clinical care. However, informed consent was obtained from the patient and their legal guardian for participation and publication. Consent to Publish Written informed consent was obtained from the patient’s next of kin for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Acknowledgments: ATB contributed to the conception and design of the case report, collected the clinical data, contributed to manuscript writing, and provided critical revisions of the manuscript. KRD: drafted the manuscript, contributed to the interpretation of the clinical findings, performed the literature review, and contributed to the writing of the manuscript. GCG assisted in the literature review and contributed to the writing of the manuscript. EPL: supervised the study, provided methodological input, and critically revised the manuscript Competing interests: The authors declare that there are no conflicts of interest. Funding: This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Underlying data: All data underlying the results are available as part of the article, and no additional source data are needed. References Barp A, Sansone VA, Lunetta C. 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16:22:21","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82083,"visible":true,"origin":"","legend":"","description":"","filename":"10703d6ec49a4dfcb6d5d4e3235984971structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7783546/v1/4454f292fe9f78834382b83b.xml"},{"id":97269440,"identity":"357ab77c-f456-49c0-ab39-3ee4abd37409","added_by":"auto","created_at":"2025-12-02 14:52:46","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":91541,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7783546/v1/94341692b17274a27da13172.html"},{"id":97269433,"identity":"9d1f329c-412e-482f-b609-479747c1ac01","added_by":"auto","created_at":"2025-12-02 14:52:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":267187,"visible":true,"origin":"","legend":"\u003cp\u003ePatient disease progression\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7783546/v1/be7413b6ce6d2660d99100df.png"},{"id":97269434,"identity":"635aec6a-da38-43e9-809d-4be2929247a7","added_by":"auto","created_at":"2025-12-02 14:52:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":88947,"visible":true,"origin":"","legend":"\u003cp\u003eBilateral atrophy of the thenar and hypothenar muscles\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7783546/v1/f33bfcdf9333ce707eb4ee66.png"},{"id":97372650,"identity":"d6571938-b547-42a4-9ebb-d4371a1a995a","added_by":"auto","created_at":"2025-12-03 16:32:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":901148,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7783546/v1/f69fde08-f4dc-408d-9e99-7db96aa98f12.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBetween Hope and Acceptance: A Case Report of Als and Realities of Palliative Care in Indonesia\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eAmyotrophic lateral sclerosis\u003c/em\u003e (ALS), also known as \u003cem\u003eLou Gehrig's disease\u003c/em\u003e, is a neurodegenerative disease characterized by progressive muscle weakness that is often sporadic in nature and affects \u003cem\u003eupper\u003c/em\u003e (UMNs) and \u003cem\u003elower motor neurons\u003c/em\u003e (LMNs). (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) \u003cem\u003eAmyotrophy\u003c/em\u003e refers to muscle fiber atrophy causing weakness and fasciculations, whereas \u003cem\u003elateral sclerosis\u003c/em\u003e refers to atrophy of the anterior and lateral corticospinal tracts due to degeneration and gliosis. Although the exact cause is not yet understood, several theories suggest a link to genetic mutations, glutamate imbalance, neuroinflammation, and mitochondrial dysfunction. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The main cause of mortality is respiratory failure, which occurs approximately 3\u0026ndash;5 years after onset. In addition to motor weakness, some patients also experience cognitive or behavioral changes, including frontotemporal dementia. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe prevalence of ALS is reported to be 6/100,000 people, with a peak incidence in people over 50 years of age. To date, few cases of ALS have been reported in Indonesia. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Studies have shown that the incidence rate of ALS will increase by 69%, from 222,801 in 2015 to 376,000 in 2040. The Global Burden of Disease states that there was a 4.5% increase to 330,918 cases from 1990\u0026ndash;2016 in America. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eALS is a fatal disease for which no curative treatment has yet been identified. The management of ALS aims to prevent progression and optimize the quality of life of patients. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Riluzole, edaravone, and \u003cem\u003esodium pheynulbutirate\u003c/em\u003e have been approved by \u003cem\u003ethe United States Food and Drug Administration\u003c/em\u003e (US-FDA) as drugs to improve the survival rate of ALS patients. Oral riluzole was the first preparation approved by the FDA. Riluzole works by reducing glutamate excitotoxicity. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Edaravone is an antioxidant that suppresses oxidative stress. Edaravone has been available in Indonesia since 2020, but its distribution is still limited. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) A 24-week edaravone therapy regimen was found to reduce \u003cem\u003ethe Revised Amyotrophic Lateral Sclerosis Functional Rating Scale\u003c/em\u003e (ALSFRS-R) score by 33%, but subsequent studies have not reported significant outcomes. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The limited options for pharmacological therapy for ALS are one factor contributing to the poor prognosis of patients according to ALSFRS-R scores. This case report aims to describe the challenges \u003cem\u003eassociated with the\u003c/em\u003e ALS \u003cem\u003etreatment gap\u003c/em\u003e faced in clinical practice in Indonesia.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 39-year-old woman was brought to the Emergency Department (ED) on July 26, 2025, complaining of shortness of breath after choking. The patient had previously experienced weakness in both legs since November 2023, starting with the left leg, followed by the right leg (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The patient became \u003cem\u003ebedridden\u003c/em\u003e because of these complaints. In January 2024, the weakness in her legs worsened, and since May 2025, the patient has been unable to move both legs, with only slight movement remaining in the tips of her right toes. The weakness then spread to both arms, which began in May 2025. The patient also complained of shortness of breath, which had been felt since February 2025 and worsened, leading to a visit to the emergency department on 5 July 2025. The patient was diagnosed with ALS while working in Germany, with treatment consisting of Riluzole 2\u0026times;50 mg. The patient had a history of hypothyroidism and was treated with L-thyroxine 2\u0026times;100 mcg. There were no complaints of visual disturbances.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eVital sign examination revealed tachypnea (29 breaths per minute), a blood pressure of 132/90 mmHg, a \u003cem\u003eheart rate\u003c/em\u003e of 91 beats per minute, a temperature of 36\u0026deg;C, and an oxygen saturation of 93% (\u003cem\u003eroom air\u003c/em\u003e). Neurological examination of the extremities revealed tetraparesis and muscle strength 333/333; 111/111, with bilateral atrophy of the thenar and hypothenar muscles (Fig.\u0026nbsp;2). Physiological reflexes were decreased, but pathological Hoffman\u0026ndash;Tromner reflexes were present (+/+). The patient then underwent a complete blood count, electrolyte panel, and thyroid panel (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A chest X-ray revealed signs of right hemidiaphragmatic paralysis. The initial thyroid panel results indicated hypothyroidism, but this is now controlled (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 2\u003c/b\u003e. Bilateral atrophy of the thenar and hypothenar muscles\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\u003ePatient Laboratory Test Results\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\u003eExamination\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5/7/25\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26/7/25\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematocrit (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRed blood cells (10⁶/\u0026micro;L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets (\u003csup\u003e10\u0026sup3;\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e376\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e447\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite blood cells (10\u003csup\u003e\u0026sup3;\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e11.54 (H)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasophils (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEosinophils (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e12.1 (H)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e10.2 (H)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophils (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e44.6 (L)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e47.5 (L)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocytes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSodium (mEq/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium (mEq/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFT4 (pmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e40.53 (L)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTSH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4.68 (Hour)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.834\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\u003eBefore undergoing therapy in Indonesia, the patient had already undergone supporting examinations in Germany. The examinations conducted were as follows: lumbar puncture with normal results; sural nerve biopsy showing neuropathy; and autoimmune and infection panels, including \u003cem\u003eTransthyretin Amyloidosis, Antinuclear Antibody\u003c/em\u003e, C1q-ak, \u003cem\u003eAnti-Thyroid Peroxidase Antibody, and Anti-Cytomegalovirus IgG\u003c/em\u003e, all of which were negative. \u003cem\u003eComputed tomography\u003c/em\u003e (CT) and \u003cem\u003emagnetic resonance imaging\u003c/em\u003e (MRI) scans \u003cem\u003eof the spine\u003c/em\u003e at the German hospital revealed normal results. The diagnosis of ALS was confirmed via the El Escorial Classification and \u003cem\u003eAwaji\u003c/em\u003e criteria. The electromyography (EMG) results revealed denervation of the cervical, thoracic, and lumbar regions. The patient's El Escorial score indicated \u003cem\u003edefinite\u003c/em\u003e ALS with an ASLFRS-R score of 20 (20\u0026ndash;25% chance \u003cem\u003eof survival\u003c/em\u003e at 9 months). On the basis of the clinical findings, the patient was categorized as King's Stage 3, characterized by tetraparesis and dyspnea due to bulbar palsy with muscle atrophy.\u003c/p\u003e\u003cp\u003eThe patient then underwent spirometry, which revealed \u003cem\u003erestrictive lung disease\u003c/em\u003e characterized by \u003cem\u003ea forced vital capacity\u003c/em\u003e (FVC) of 38%. The patient was recommended to receive oxygen therapy via \u003cem\u003econtinuous positive airway pressure\u003c/em\u003e (CPAP). Two days after hospitalization, the patient was discharged with tetraparesis, and her dyspnea improved. Riluzole therapy was continued without any additional therapy. During psychological counseling sessions, the patient admitted to feeling afraid of the journey toward death but had accepted their condition and was prepared to face the end. The patient was discharged with supportive and palliative care management.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by gradual muscle paresis leading to \u003cem\u003erespiratory distress\u003c/em\u003e. This disease causes voluntary motor degeneration, starting from the motor neurons in the motor cortex to \u003cem\u003ethe neuromuscular junction.\u003c/em\u003e (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) The pathogenesis of ALS is not fully understood and is multifactorial.\u003c/p\u003e\u003cp\u003eThe main pathomechanism of ALS involves disruption of protein homeostasis, particularly the intracellular protein degradation mechanism. There are two main pathways responsible for protein degradation, namely, the \u003cem\u003eubiquitin‒proteasome\u003c/em\u003e system (UPS) and the autophagy mechanism. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) The UPS pathway functions to destroy proteins that have been identified for elimination. \u003cb\u003e11)\u003c/b\u003e In addition, the autophagy pathway plays a role in breaking down large protein aggregates that cannot be handled by the UPS. Dysfunction of these two systems leads to the accumulation of abnormal proteins such as TDP-43, which triggers cellular stress, apoptosis, and the formation of cytoplasmic inclusions known as Bunina bodies. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eEpidemiologically, approximately 85\u0026ndash;90% of ALS cases are sporadic, whereas the remaining 10% are autosomal dominant. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) One of the most widely studied genetic mutations is the \u003cem\u003esuperoxide dismutase 1\u003c/em\u003e (SOD1) gene on chromosome 21. This gene functions to convert superoxide free radicals into oxygen and hydrogen peroxide, thereby protecting cells from oxidative stress. SOD1 mutations can trigger \u003cem\u003ethe unfolded protein response\u003c/em\u003e, endoplasmic reticulum stress, and motor neuron death through the activation of autophagy and the apoptosis pathway. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Five main interrelated mechanisms are involved in the pathophysiology of ALS: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) neuronal protein homeostasis disorders; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) RNA metabolism dysfunction; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) glutamate excitotoxicity; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) mitochondrial dysfunction; and (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) the inhibition of intraneuronal axoplasmic transport. These processes lead to the destruction of motor neurons, both Betz cells in the motor cortex and anterior horn cells in the spinal cord, through retrograde axonal degeneration. This process causes the \u003cem\u003egradual\u003c/em\u003e manifestation \u003cem\u003eof paralysis\u003c/em\u003e in ALS patients.\u003c/p\u003e\u003cp\u003eThe lack of epidemiological data poses a challenge in identifying \u003cem\u003ethe burden of disease\u003c/em\u003e from ALS. \u003cem\u003eThe cost of illness\u003c/em\u003e (COI) for ALS patients in Germany reaches \u0026euro;78,256 per person per year. Among these costs, 35.9% are direct medical costs, 49.1% are direct nonmedical costs, and 15% are indirect costs. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) The economic burden of ALS stems not only from medical care costs but also from the need for nonmedical support and loss of productivity due to the disease. Data \u003cem\u003eon the burden of\u003c/em\u003e ALS in Indonesia are still very limited. There are only two follow-up studies related to ALS in Papua. In 2012, there were 46 cases of ALS and/or parkinsonism, with a population range of 20,900 (2001\u0026ndash;2012). A previous study reported 57 clinically confirmed cases of ALS from 1974\u0026ndash;1981. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) The prevalence rate of ALS in this study ranged from 27\u0026ndash;240/100,000 individuals. The incidence and prevalence of ALS in this study were found to be higher than the global incidence (2/100,000) and prevalence (6/100,000) figures in 2013. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) The highest incidence of ALS was found after the age of 50; therefore, previous studies assumed that the prevalence of ALS in Indonesia was only 2,500 individuals. This figure was obtained only by assuming that 15% of the Indonesian population was over 50 years of age in 2015. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) These findings indicate that there is \u003cem\u003eunderreporting\u003c/em\u003e and \u003cem\u003eunderdiagnosis\u003c/em\u003e of ALS cases in Indonesia, leading to an iceberg phenomenon in the actual incidence and prevalence rates of ALS in Indonesia. This causes major \u003cem\u003epitfalls\u003c/em\u003e in the burden of disease from ALS cases.\u003c/p\u003e\u003cp\u003eTo date, there is no definitive treatment for ALS, and treatment is only symptomatic. According to \u003cem\u003ethe American Academy of Neurology, 2009\u003c/em\u003e, the first-line pharmacological treatment for ALS is riluzole and edaravone, and the second-line treatment is sodium phenylbutyrate/taurursodiol, along with other experimental agents. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The current pharmacological agent and its properties comparison for ALS is presented in (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eComparison of therapies for ALS\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRiluzole\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEdaravone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eSodium\u003c/em\u003e Phenylbutyrate/Taurursodiol\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMechanism of Action\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGlutamate antagonist (antitoxicity)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAntioxidant (targets oxidative stress)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMitochondrial and endoplasmic reticulum protection\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eImpact on ALS progression\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSlightly delays ALS progression; extends survival by 2\u0026ndash;3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSlightly delays ALS progression; extends survival by 6 months (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSlight improvement in function and reduction in progression\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDosage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2x50 mg/day orally (maximum 100 mg/day) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntravenous dose: 60 mg/day (maximum dose not yet determined)\u003c/p\u003e\u003cp\u003eOral suspension dosage: 105 mg/5 ml daily (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 dose of medication (3 g \u003cem\u003eSodium Phenylbutyrate\u003c/em\u003e\u0026thinsp;+\u0026thinsp;1 g Taurursodiol) once daily for 3 weeks, then twice daily\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDuration of use\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLifetime\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFor 14 days, followed by 14 days without medication, and the cycle is repeated for life\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eInitial dose: 1 dose of medication daily for 21 days\u003c/p\u003e\u003cp\u003eMaintenance dose: 1 dose of medication twice daily (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSide effects\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsthenia, nausea, impaired respiratory function, gastrointestinal symptoms, and hepatotoxicity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHypoesthesia, \u003cem\u003egait imbalance\u003c/em\u003e, headache, and skin conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGastrointestinal symptoms (diarrhea, nausea, hypersalivation, and \u003cem\u003eabdominal cramps\u003c/em\u003e) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSafety\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdverse events occurred in 5% of patients with the following symptom composition: asthenia a (19%), nausea (16%), decreased respiratory function (10%), hypertension (5%), and abdominal pain (5%). Serious events had a prevalence of 11.4% of all adverse events. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHypoesthesia occurred in 38% of cases, and pancreatitis occurred in 1 out of 100\u0026ndash;1,000 patients with and edaravone consumption. No deaths or serious events were reported. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUnexpected events included gastrointestinal disorders (67%), musculoskeletal disorders (43%),, and other systemic disorders (\u0026gt;\u0026thinsp;5%). For serious events, the prevalence was 12%, with the prevalence of treatment-related deaths still unknown. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALSFRS-R score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo significant changes were observed at 6 or 12 months of treatment. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRate of change in ALSFRS-R score: -5.01 to -7.5 points over 24 weeks. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRate of change in ALSFRS-R score: -1.24 points/month\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\u003eCompared with the placebo, the administration of 100 mg of Riluzole increased the probability of \u003cem\u003e1-year tracheostomy-free survival\u003c/em\u003e by 9%. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Riluzole significantly prolonged \u003cem\u003ethe survival period\u003c/em\u003e by 2 months to 22 months compared with patients who did not receive Riluzole, which was 20 months. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) The progression of bulbar function decline after 12 months of 100 mg Riluzole was found to be 2.06 times slower than that of the placebo. The degradation of extremity function was 3.94 times slower after the administration of 100 mg of Riluzole for 12 months. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Compared with edaravone, riluzole was found to prolong life expectancy in early-stage ALS patients, whereas edaravone is only a symptomatic therapy. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) In vitro studies have shown that the combination of Riluzole and \u003cem\u003esodium phenylbutyrate\u003c/em\u003e results in lower SOD1 concentrations in the spinal cord, intestine and cerebral cortex than does monotherapy. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Further pharmacovigilance studies are not yet available.\u003c/p\u003e\u003cp\u003eThe limitations of supportive therapy make palliative therapy an important part of comprehensive ALS management. Although physical, occupational, and speech therapy can help maintain independence, nutritional and ventilation therapy aims to maintain patients\u0026rsquo; physical well-being. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The progression of ALS causes respiratory and bulbar muscle paralysis, which is important for maintaining airway patency. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) The accumulation of CO₂ due to respiratory muscle weakness triggers hypercapnia and organ hypoperfusion, including in the central nervous system, which disrupts lymphatic function, such as \u003cem\u003etoxin clearance\u003c/em\u003e and sclerosis, and exacerbates cerebral vascular damage. These disorders further exacerbate the progression and clinical outcomes of ALS. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003cem\u003eNoninvasive ventilation\u003c/em\u003e (NIV) is one of the main components of symptomatic management in individuals with ALS to improve survival and quality of life. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) \u003cem\u003eThe European Federation of Neurological Societies (\u003c/em\u003eEFNS) recommends initiating NIV in patients with respiratory symptoms or if FVC\u0026thinsp;\u0026lt;\u0026thinsp;80%, SNIP\u0026thinsp;\u0026lt;\u0026thinsp;40 cmH₂O, pCO₂ \u0026gt;45 mmHg, or nocturnal desaturation is observed. Other studies have shown that earlier NIV (FVC\u0026thinsp;\u0026gt;\u0026thinsp;80%) results in a slower decline in FVC than does placebo. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e\u003cp\u003ePsychological aspects are crucial in palliative ALS care, as depression and anxiety are common. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Psychotherapy and pharmacotherapy interventions such as fast-acting anxiolytics, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs) can reduce depression and anxiety, as supported by palliative care studies. (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) Physical and occupational therapy support motor function adaptation, although evidence of their effectiveness is still limited. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) There are eight predictors of transition to palliative care, including young onset and bulbar palsy, as found in this case. Other predictors are a definitive diagnosis of ALS, delayed diagnosis, decreased \u003cem\u003eforced vital capacity\u003c/em\u003e, rate of progression, \u003cem\u003ecoexisting\u003c/em\u003e frontotemporal dementia, and the presence of C9 or F72 \u003cem\u003erepeat\u003c/em\u003e expansions. (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eALS management in Indonesia requires a comprehensive reform strategy to formulate a standardized ALS \u003cem\u003eclinical pathway\u003c/em\u003e. The algorithm is aimed at early identification with the support of EMG and MRI, as well as clinical classification on the basis of the \u003cem\u003eGold Coast criteria\u003c/em\u003e and \u003cem\u003eEl Escorial\u003c/em\u003e diagnostic criteria. The formulation of this \u003cem\u003epathway\u003c/em\u003e can be based on Kings staging, the ASLSFRS-R, and the Norris scale. Supporting examinations such as genetic testing, neuron/myocyte biopsy, and autoimmune panels are still limited. Currently, only edaravone is available, \u003cem\u003ewhereas riluzole and sodium\u003c/em\u003e phenylbutyrate-taurursodiol are not yet officially available, requiring independent importation, causing delays in therapy and worsening clinical outcomes, including the progression of onset.\u003c/p\u003e\u003cp\u003eIt is hoped that through this case report, pharmacological preparations such as \u003cem\u003eriluzole, sodium phenylbutyrate\u003c/em\u003e, and taurursodiol will become available in Indonesia. Delays in the administration of pharmacological management can significantly reduce the survival rate of ALS patients. In addition, early assessment of accompanying symptoms such as dyspnea due to bulbar palsy and the need for medical aids such as CPAP should be standardized in all secondary facilities. The delayed diagnosis of ALS patients, especially \u003cem\u003ethose with bulbar onset\u003c/em\u003e, is associated with a poorer \u003cem\u003equality of life\u003c/em\u003e, a greater need for NIV and \u003cem\u003epercutaneous gastrotomy\u003c/em\u003e, and a lower \u003cem\u003esurvival rate\u003c/em\u003e. (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case represents a concrete example of the challenges of managing ALS in Indonesia. Limited access to \u003cem\u003egold standard diagnostic\u003c/em\u003e modalities and pharmacological and nonpharmacological management remains one of the predictors of clinical outcomes for ALS patients in Indonesia. This case report also highlights palliative therapy options that can improve \u003cem\u003ethe quality of life\u003c/em\u003e of ALS patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was not required for this case report, as it does not involve research on human subjects beyond standard clinical care. However, informed consent was obtained from the patient and their legal guardian for participation and publication. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s next of kin for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eATB contributed to the conception and design of the case report, collected the clinical data, contributed to manuscript writing, and provided critical revisions of the manuscript. KRD: drafted the manuscript, contributed to the interpretation of the clinical findings, performed the literature review, and contributed to the writing of the manuscript. GCG assisted in the literature review and contributed to the writing of the manuscript. EPL: supervised the study, provided methodological input, and critically revised the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnderlying data:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data underlying the results are available as part of the article, and no additional source data are needed.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBarp A, Sansone VA, Lunetta C. Challenges in diagnosis of motor neuron disease: A case series of ALS mimic syndromes. 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Neurology. 1 November 2016;87(18):1878\u0026ndash;83.\u003c/li\u003e\n\u003cli\u003eFulton JJ, Newins AR, Porter LS, Ramos K. Psychotherapy Targeting Depression and Anxiety for Use in Palliative Care: A Meta-Analysis. J Palliat Med. 2018 July;21(7):1024\u0026ndash;37.\u003c/li\u003e\n\u003cli\u003eVan Damme P, Al-Chalabi A, Andersen PM, Chi\u0026ograve; A, Couratier P, De Carvalho M, et al. European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD). Eur J Neurol. 2024 June;31(6):e16264.\u003c/li\u003e\n\u003cli\u003eGould RL, Coulson MC, Brown RG, Goldstein LH, Al-Chalabi A, Howard RJ. Psychotherapy and pharmacotherapy interventions to reduce distress or improve well-being in people with amyotrophic lateral sclerosis: A systematic review. Amyotroph Lateral Scler Front Degener. 27 August 2015;16(5\u0026ndash;6):293\u0026ndash;302.\u003c/li\u003e\n\u003cli\u003eMercadante S, Al-Husinat L. Palliative care in amyotrophic lateral sclerosis. Journal of Pain and Symptom Management. 2023 Oct;66(4):e485\u0026ndash;99.\u003c/li\u003e\n\u003cli\u003eGwathmey KG, Corcia P, McDermott CJ, Genge A, Sennf\u0026auml;lt S, de Carvalho M, et al. Diagnostic delay in amyotrophic lateral sclerosis. Eur J Neurol. 2023 Sept;30(9):2595\u0026ndash;601.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ALS, ALS Palliative Care, ALS Treatment, Case Report, Quality of Life","lastPublishedDoi":"10.21203/rs.3.rs-7783546/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7783546/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\u003cp\u003eAmyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease involving upper and lower motor neurons. However, the scarcity of However, the scarcity of pharmacotherapy choices pose significant challenges in managing ALS. This study aims to highlight the realities of ALS management in Indonesia.\u003c/p\u003e\u003cp\u003eCase Report\u003c/p\u003e\u003cp\u003eA 39-year-old woman presented with dyspnoea and limb weakness in January 2024, which progressed to tetraparesis by July 2025. Her vital signs included a blood pressure of 102/74 mmHg, heart rate of 75 bpm, respiratory rate of 27x/min, temperature of 36\u0026deg;C, and oxygen saturation of 93% (room air). Neurological examination revealed tetraparesis (333/333; 111/111), with bilateral thenar-hypothenar atrophy. Physiological reflexes were diminished, and pathological reflexes were positive. The patient was admitted in early July with similar symptoms. Special examinations via lumbar puncture, magnetic resonance imaging (MRI), and spine CT scans revealed normal results. TTR-amyloidosis antibody, ANA, and anti-TPO test results were negative. Sural nerve biopsy indicated neuropathy. Electromyography revealed denervation from the cervical to lumbosacral regions, leading to a diagnosis of definite ALS (El Escorial criteria, King's grade 3). The ASLFRS-R score was 20. The patient received Riluzole 2x50 mg (from Germany) along with psychological support, physiotherapy, home care, and palliative treatment.\u003c/p\u003e\u003cp\u003eDiscussion and Conclusion\u003c/p\u003e\u003cp\u003eThis case highlights the limited access to diagnostic tests and management for ALS in Indonesia. Edaravone and riluzole are the only available symptomatic treatments in Indonesia; unfortunately, their distribution are limited. Palliative and supportive care are currently the only options available for ALS patients in Indonesia. Uncertainty regarding the outcome affects the patient's quality of life.\u003c/p\u003e","manuscriptTitle":"Between Hope and Acceptance: A Case Report of Als and Realities of Palliative Care in Indonesia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 14:52:41","doi":"10.21203/rs.3.rs-7783546/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-12-15T04:48:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T10:57:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289601587873224327353185699034723364410","date":"2025-12-06T16:49:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-05T06:53:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62847614495066853171618734728106681636","date":"2025-12-03T06:40:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299169994870706329569616004926775356593","date":"2025-11-30T15:31:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22302698090464414875906530843293274430","date":"2025-11-28T15:19:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-28T14:37:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-06T07:02:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-07T23:13:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-07T23:12:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-10-05T08:03:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"992d5418-d7a5-440f-a373-a2b751b839f2","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-02T14:52:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-02 14:52:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7783546","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7783546","identity":"rs-7783546","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}