Received 2024-11-21

Revised 2025-01-24

Accepted 2025-03-25

Introduction

Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease or Charcot disease, is a specific, swiftly progressive, paralytic, lethal disorder characterized by degeneration of upper motor neurons in the brain cortex and lower motor neurons in the brainstem and spinal cord [1, 2]. In 1869, Jean-Martin Charcot initially identified this condition as a pure motor neuron disease. However, nowadays, it is considered a neurodegenerative disorder that affects multiple physiological systems [3]. With a global prevalence rate of 4-6 cases per 100,000, ALS stands as the foremost motor neuron disease and ranks third among neurodegenerative disorders, affecting individuals across all racial and ethnic backgrounds. [4-6] The majority of ALS patients are between 50 and 65 years old, with only about 5% under 30. The occurrence significantly decreases beyond the age of 80 [7, 8]. The typical survival time for ALS patients after symptom onset is about three years [9]. only 5-10% of patients live beyond 10 years after diagnosis [4]. Factors associated with poorer prognosis include an older age when the symptoms first appear, a faster rate of progression at the onset of the disease, and the initial involvement of bulbar muscles [10]. Due to the absence of definitive laboratory tests or imaging biomarkers, the diagnosis is based on clinical manifestations, and an electromyogram can help confirm the diagnosis [11].

The “Revised El Escorial Criteria” have been established for the diagnosis of ALS; the components of these criteria are shown in Table-1 [12]. Based on the Awaji-Shima consensus, ALS has three diagnostic classifications, as shown in Table-2 [13]. Due to its progressive and degenerative nature, ALS affects individuals physically, emotionally, and socially. Rehabilitation is the process of helping disabled patients improve their condition of physical function. It plays a crucial role in supporting ALS patients by addressing the various challenges they face. Because ALS is incurable, by implementing appropriate rehabilitation strategies and clinical support, healthcare professionals can help improve the physical and emotional well-being of ALS patients and extend their survival.

This review aims to provide various rehabilitation strategies, including physical therapy, occupational therapy, speech therapy, and respiratory therapy, that can be employed to improve patient autonomy, functionality, and safety and overall enhance their quality of life while also reducing symptoms associated with the disease. It’s important to note that the specific rehabilitation strategies mentioned in the review will depend on individual patient needs and preferences.

Overview of Amyotrophic Lateral Sclerosis:

Pathophysiology of ALS

ALS is classified as sporadic ALS (sALS) with unknown etiology in more than 90% of cases, which do not affect first-degree relatives [14], and the familial form of ALS (fALS), which accounts for nearly 5-10% of cases, characterized by a hereditary pattern. These cases typically appear at an earlier age of onset [15, 16].

While the exact reasons for sALS remain unclear, there are various risk factors have been suggested. These factors include age, smoking, low physical fitness, head injuries, cancer history, viral infections (such as poliomyelitis, HHV-6, and HHV-8), as well as occupational and environmental variables such as chemical exposure, pesticide exposure, metal exposure, β-methylamino-L-alanine, and electromagnetic field exposure [17, 18].

Recently, several genetic risk factors have been identified for sALS, too; for example, mutations in the C9orf72, SOD1, TARDBP, and FUS genes are associated with both familial and sporadic ALS [19], So it seems that ALS is a multifactorial disease caused by both genetic and various environmental factors [20].

Clinical Presentation of ALS

The diagnosis of ALS is clinical, and it is confirmed by the presence of the signs of both upper motor neuron (UMN) and lower motor neuron (LMN) in a person with unexplained weakness [12]. UMN disturbance features include spasticity, weakness, and hyperreflexia. By contrast, LMN involvement causes fasciculations, wasting, and weakness [21]. “Split-hand” is one of the characteristic features of ALS that refers to a disproportionate loss of the thenar muscles combined with the first dorsal interossei [22]. ALS has two main clinical manifestations. Limb onset that characterized by MN degeneration signs in limbs and bulbar-onset in about 25-30% of cases characterized by dysarthria, dysphonia, and dysphagia [23, 24]. Rarely, atypical presentations, including weight loss, cognitive impairment, behavioral changes, or respiratory failure, are the initial manifestations of ALS [25, 26].

During the progression of ALS, the respiratory muscles also weaken, which diminishes respiratory muscle strength, causing an ineffective cough and alveolar hypoventilation as a consequence [27]. Early signs of respiratory involvement include headaches, daytime fatigue, and orthopnea [28]. As respiratory muscle fatigue worsens, patients may experience respiratory failure, often precipitated by pneumonia. Eventually, when patients experience dyspnea at rest, death is imminent [29].

In the late stages of the disease, patients may experience weakness in their axial muscles, which can cause head drop. Additionally, around one-third of patients may experience uncontrollable laughing and crying, referred to as the pseudobulbar effect [30].

Because of weak control of orofacial and Palatino-lingual muscles, facial muscle weakness, and tongue spasticity, excessive drooling, also known as sialorrhea, is considered among the most incapacitating symptoms in ALS [31, 32].

Overall, more than 15% of ALS patients have frontotemporal dementia (FTD) [33].

Different factors, such as spasticity, muscle cramps, contractures, and skin pressure, cause pain, which is a common complaint among ALS patients [34].

Current Treatment Options for ALS

Despite many research and clinical trials, there is no definitive treatment available for ALS.

Until now, there are two approved treatments for ALS, including Riluzole and Edaravone [35].

Riluzole, an anti-glutamatergic drug that inhibits the presynaptic release of glutamate, is a well-tolerated drug in ALS patients, even in the advanced stage of the disease, which can extend the median survival time by two to three months and enhance the likelihood of survival in the first year by 9% [36-38].

It should be taken 50 mg orally every 12 hours. Frequent blood tests to monitor liver function are essential before and during treatment with Riluzole. When the serum levels of transaminases go three times up to normal value, treatment should be stopped [36].

Edaravone (MCI-186) is an antioxidant and a free radical scavenger, which was originally approved as a treatment for cerebral infarction in Japan [39]. It seems to act as a protective agent [40]. The common side effects of it are bruising and disruption in walking. So far, this drug does not have oral administration. Thus, it is administered intravenously to modify ALS clinical outcome [34].

Recently, novel gene therapies targeting potential molecular mechanisms have been developed for the treatment of motor neuron diseases, including ALS. Although regulatory approvals for these therapies are limited, ongoing trials provide hope for effective treatments [41].

Rehabilitation Interventions for ALS

Rehabilitation for ALS is a comprehensive and multidisciplinary approach. This review delves into the core aspects of rehabilitation in ALS, encompassing Physical Therapy, Occupational Therapy, Speech and Language Therapy, and Respiratory Therapy. Each of these therapies plays a crucial role in addressing the challenges posed by ALS. Physical Therapy focuses on maintaining mobility and preventing complications from muscle weakness. Occupational Therapy aids in adapting daily activities and environments to preserve autonomy. Speech and Language Therapy is essential for communication and swallowing difficulties, while Respiratory Therapy is critical for managing respiratory insufficiency, a common complication in ALS.

Physical Therapy

Stretching and Range of Motion Exercises

Loss of range of motion (ROM) leads to painful adhesive capsulitis and even complex regional pain syndrome [42]. So, ROM exercises are recognized as the initial treatment approach for managing spasticity and alleviating muscle spasms that cause pain in individuals diagnosed with ALS [43].

Although specific recommendations may vary depending on the individual’s stage of the disease, it is generally recommended to perform 1-2 sessions of active and passive ROM exercises daily to enhance or maintain range of motion [44].

ALS patients have weaker muscles, and there is an imbalance between agonist and antagonist muscles, which predisposes them to muscle shortening, joint contracture, and poor postures such as claw hands. Therefore, stretching could enhance flexibility, maintain good alignment of body segments, improve joint mobility, and prevent contractures [45].

Therefore, stretching exercise is a part of standard care for patients with ALS that should be encouraged to be done daily at the beginning of the disease [46]. It can be performed with a caregiver’s assistance when the patient becomes unable to perform stretches independently [47].

Strengthening Exercises

Resistance exercise improves muscle force/power, induces muscle hypertrophy, maintains skeletal muscle function, and avoids disability [48]. These exercises have a beneficial effect on the quality of life for individuals with ALS; nonetheless, they cannot prolong life expectancy [49]. Studies showed that those who engaged in strength and resistance exercises experienced a lower incidence of falls compared to the group that focused on the range of motion and stretching exercises [50].

It is recommended to begin muscle strengthening exercises immediately after diagnosis, as earlier initiation results in greater improvement. Continuation of these exercises is also an important factor, as a positive effect can be observed approximately a year after the initiation of exercises [51].

The exercise plan should focus on muscles that demonstrate a strength level above three on the Manual Muscle Testing scale and patients should closely be monitored for signs of overuse during these exercises [52]. Because some studies showed that high-intensity resistance training may increase the risk or exacerbate the progression of ALS [53, 54]. This happens because of oxidative stress, glutamate excitotoxicity, and heightened calcium loads, which promote selective degeneration of susceptible motor neurons [55, 56]. Muscle soreness and fatigue lasting over 30 minutes post-exercise are the signs of overuse and indicate the necessity of exercise plan modification [57].

Respiratory Muscles Training

Involvement of respiratory muscles leads to decreased subglottic air pressure, ability to cough and clear secretions and consequently increases the risk of pulmonary infection [58, 59].

The forced vital capacity (FVC) test measures the amount of air a person can forcefully exhale after taking a deep breath. It is closely associated with both disease progression and survival in ALS patients. When FVC falls below 50%, it indicates the beginning of respiratory failure, which is a critical stage in the disease [60].

Respiratory muscle training (RMT) in patients with ALS can be used as an adjunctive therapy that improves ventilator function and respiratory strength [61]. RMT can be divided into two types: training for the muscles involved in inhalation, known as inspiratory muscle training (IMT), and training for the muscles involved in exhalation, known as expiratory muscle training (EMT). The efficacy of EMT is less clear than IMT [62]. However, prior studies showed that it is an effective tool for improving maximal Peak cough flow (PCF) in individuals with neuromuscular diseases, and 5-week training improves respiratory and bulbar function in individuals with ALS [62, 63]. RMT can also have a positive effect on respiratory muscle endurance. While high load and low-speed training will increase muscle strength, engaging in high-speed training with low resistance enhances endurance [64, 65].

RMT protocols should consider 4 components known as FITT (Frequency, Intensity, Time, and Type). However, the optimal FITT parameters for ALS-specific RMT remain undefined, underscoring the need for further research to establish effective respiratory management guidelines [66].

POWERbreathe® is a device utilized for the training of inspiratory muscles. When used as a supplementary therapy alongside standard care in neuromuscular conditions, this device provides advantages such as improving the strength of inspiratory muscles and lowering resting heart rate [67, 68].

Table-3 provides a summary of physical therapy recommendations in ALS. Overall, although there is no definite evidence, exercise appears to be one of the few modalities that may enhance function in ALS patients. In addition to improving function, it may also provide some control over the disease.

Occupational Therapy

Activities of Daily Living Training

Activities of daily living (ADL) training is a crucial component of rehabilitation in ALS patients. It focuses on assisting individuals with maintaining as much independence as possible in performing everyday tasks that are essential for self-care and daily living. Unfortunately, few studies have been done on ADL disability in ALS, but A large variety of adaptive devices are accessible to help them perform ADLs, although no single device is suitable for all patients or all stages of the illness.

Mobility is essential for performing ADLs. ALS can lead to gait alterations and subsequently cause decreased mobility, which in turn increases the risk of falls and fractures. It has been reported that approximately 33% of ALS patients experience falls [69]. Therefore, training may involve techniques and assistive devices to facilitate safe transfers from one position to another.

Various types of mobility aids, including canes, crutches, and walkers, are available for ALS patients. The prescription of each aid is contingent upon the extent of weakness in both the upper and lower limbs, as well as the grip strength. Canes can serve as valuable aids for individuals experiencing gait instability due to weakness. If hand weakness is a concern, canes with a horizontal grip can be particularly beneficial [70]. However, crutches may not be a suitable option in these cases, as their use requires a high level of strength and coordination in the upper limbs. Walkers offer substantial support and are recommended for individuals with moderate to severe balance issues. 4-wheeled walkers, in contrast to standard ones, provide the advantage of not needing to be lifted. However, it’s essential to ensure that the patient can maneuver it safely [46]. Wheelchairs (manual or electric), mobility scooters, and stair lift systems are other examples of products that could be used to facilitate transportation indoors and outdoors [71]. Orthotic devices such as ankle-foot orthoses, night splints, wrist extension orthoses, thumb positioning orthoses, and cervical collars are also employed to aid in enhancing function and mobility among individuals with ALS [72].

One part of basic ADLs includes personal care such as hygiene or grooming, dressing, and toileting. Occupational therapists can evaluate the needs of patients and provide equipment to enhance independence and function. This may include specialized utensils to improve grip for self-feeding, raised toilet seats, grab bars, shower chairs, and transfer devices for bathing [73].

Energy Conservation Strategies

One of the frequent symptoms of ALS is fatigue (in approximately 44-86% of cases), which consequently could decrease quality of life [74]. Therefore, knowing strategies for diminishing this symptom is one the crucial parts of the management of ALS patients.

Some energy conservation strategies include sufficient rest periods throughout the day, having proper posture during activities, for example, performing tasks while sitting rather than standing, splitting fatiguing activities into several smaller and easier components, prioritizing activities emphasizing doing hard functions at the beginning, teaching ergonomic principles, and environment modification. These techniques usually are instructed by the occupational therapist [75-78].

Among the energy conservation strategies mentioned, the most commonly used and effective ones were those incorporating periods of rest, particularly those that maintained a balance between work and rest [79].

Certain assistive devices consume more energy than others. For instance, a rolling walker requires less effort compared to a standard walker. Similarly, single canes are more energy efficient than crutches or quad canes. Another factor that can influence energy expenditure is the material composition of different assistive devices utilized by patients. For instance, a lightweight carbon fiber ankle-foot orthosis is generally preferred over heavier hinged ones [80].

There are also some simple conserve energy strategies that can be helpful for ALS patients while they want to speak. First, they should avoid any noisy situation, for example, by muting TV or asking others to talk to them in a quiet situation instead of a crowded room. Also, they can use a voice amplifier to reduce effort [81, 82].

Speech and Language Therapy

Augmentative and Alternative Communication

ALS can significantly limit a person’s ability to communicate a few years after the initiation. In a way, more than 80% of patients experience difficulties with their speech and communication, and most will be unable to speak at all [83]. Recognizing this impairment is crucial because a lack of effective communication leads them to prevent engaging in various activities, resulting in social isolation, which significantly diminishes their quality of life [84].

Thus, augmentative and alternative communication (AAC) is becoming increasingly important, offering ALS patients a valuable tool to overcome the significant motor impairments they face. They also can help patients to keep their emotional connection with other people, reducing the load on caregivers and enhancing the psychological and social well-being of the patient and QOL in dysarthric ALS patients, despite lack of speech intelligibility [85]. In addition, using AAC strategies can diminish patients ‘anger and frustration experienced by individuals who have lost the ability to communicate with others using natural speech [86].

It should be kept in mind that appreciate timing for referring patients to AAC assessment and intervention is an important decision-making issue [87].

Strengthening exercise of lip and tongue may sometimes be helpful for patients to pronounce words more clearly but so far, there hasn’t been any evidence that orofacial muscle strengthening could be effective [88].

ALS patients may use non-verbal strategies for communication, which means that they send their messages by gesture, facial expression, or eye contact [86].

As long as patients ‘hand function is adequate, writing can be used instead of speaking. Devices needed are very simple, for example, paper and pencil, alphabet cards, a portable typewriter, and a letter board. These are the examples of low-tech ACC. For those who cannot rely on speaking or writing, then high-tech AAC such as brain-computer interface (BCI) and eye tracking systems should be considered as a part of palliative care [89, 90].

BCI is one of the usable devices for disabled patients with ALS, which interprets the electric signals of the brain and translates them into commands. The BCI has a virtual keyboard known as a P300 speller [91]. This virtual keyboard includes a word prediction feature that facilitates word completion and next-word prediction. It accomplishes this by presenting a list of the ten most probable words on the right side of the keyboard. One of the best features of this device is its easy operation, which does not require much learning effort [92].

For individuals whose mobility is limited to their eyes, eye-tracking-based applications could be useful, which enable them to communicate with normal people and make their lives easier [93]. A former study indicated that the worse the clinical presentation, the better acceptance was achieved by the patients [94]. As it is obvious from its mechanism of action, the necessary factor for using this technology is full ocular mobility and having appropriate visuals [95]. Fortunately, eye gaze remains intact over time, even in cases where invasive ventilation has been used [96].

Dysphagia Management

About 85% of people with ALS encounter dysphagia, or swallowing impairment, leading to aspiration and malnutrition, negative prognostic components in ALS, which increase the mortality rate by 7.7 times, Therefore, when oral intake becomes insufficient, excessively challenging, or poses safety risks, it is necessary to use alternative feeding methods for adequate nutrition to stabilize body weight [97-99].

In the initial stages of dysphagia, dietary modification including soft, semi-solid, and semi-liquid foods and some swallowing techniques such as supraglottic swallow (taking a deep breath and holding it during the swallow, and coughing immediately after swallowing), chin-tuck maneuver (pushing the base of the tongue toward the pharyngeal wall) and regulating bolus sizes can be helpful [100, 101].

High-energy supplementation with no adverse effect could stabilize body weight. Thus, the use of high-energy supplementation is suggested [102].

A reduction in body weight exceeding 5%–10% of an individual's typical weight, a BMI <20 kg/m², and dysphagia are indications for considering feeding tube placement [103]. It is important to note that enteral feeding does not need to replace oral feeding entirely and can be used to supplement oral intake.

Nasogastric tube feedings can be used for nutrition support, but they are not recommended for long-term use because they increase the risk of aspiration and are uncomfortable for patients. Also, nasogastric tubes increase oropharyngeal secretions so that they may cause ulceration [104, 105].

For most patients, endoscopic placement of a percutaneous gastrostomy (PEG) is appropriate. Patients should be referred for this procedure before their FVC decreases to 50% of the predicted value (measured in a seated position) [106], as declining FVC is associated with increased morbidity and mortality during tube placement [107].

An alternative for PEG is PRG (percutaneous radiologic gastrostomy), which can be more tolerated than PEG, especially for patients with respiratory failure, because, unlike PEG, it doesn't need any sedation, but it's not as available as PEG, and the likely of leakage and displacement is higher [108, 109].

Table-4 provides a summary of dysphagia management strategies. Overall, effective dysphagia management in ALS requires a multidisciplinary approach that includes dietary modifications, safe swallowing techniques, nutritional support, and the timely initiation of enteral feeding when indicated. Early intervention and continuous monitoring are crucial to preventing complications associated with dysphagia, thereby improving the overall quality of life for ALS patients.

Respiratory Therapy

Noninvasive Ventilation

Many ALS patients, despite mild or no respiratory symptoms, have abnormal FVC at presentation [58]. For this reason, assessment of respiratory insufficiency, including symptoms of nocturnal hypoventilation such as daytime headache and sleep disturbance, should be done at every visit [110].

Non-invasive ventilation (NIV) is applying positive pressure to the airway through any device other than the endotracheal tube [111]. This therapy in ALS patients is associated with increasing QOL and survival despite disease progression, especially in individuals with orthopnea, without having any adverse effect on caregivers'QOL or increasing their stress [112, 113]. Also, it can decrease energy consumption in ALS patients [114].

Maximum inspiratory pressure ≤ 60 cm H2O, Spo2≤ 88% for at least five continuous minutes, Paco2> 45 mm Hg, and symptoms related to hypercapnia are indications of NIV in patients with ALS [58, 115].

NIV can be delivered through different methods, including nasal masks, oronasal masks, full-face masks, and mouthpieces. In cases of chronic respiratory failure, nasal masks are used, while oronasal masks are used in emergency situations due to their ability to minimize leakage and improve the effectiveness of ventilation [116]. For patients who suffer from skin lesions, the total face mask is a possible alternative option [117]. The other way for NIV is through mouthpieces, which may be considered for patients who experience difficulty tolerating oronasal and nasal masks. Also, it can be beneficial for individuals who encounter issues such as skin lesions, eye irritation, or gastric irritation [118].

It is crucial to consider that oxygen should not be used instead of NIV because ALS patients suffer from hypoventilation with hypercapnia, not hypoxia [119].

NIPPV (noninvasive positive pressure ventilation) is currently recommended to start when FVC is less than 50% of the predicted value [120]. So far, there is no optimal titration for NIPPV pressure, but U.S. ALS clinic medical directors recommended starting this therapy at 8 cm of H20 inspiratory (IPAP) and 4 cm of H20 expiratory positive airway pressure (EPAP) [121].

The ones who use NIPPV should be monitored through pulse oximetry overnight and regular appointments with a respiratory physician should be scheduled to confirm that the pressure settings are appropriate [122].

Cough Assist Techniques

ALS is associated with a reduction of cough flow and efficacy because inspiratory muscle weakness leads to a lower depth of pre-cough inspiration, and expiratory muscle weakness decreases intrathoracic expiratory pressure [123]. Therefore, the inability to have an effective cough is one of the major problems faced by most ALS patients.

One of the first-line and low-cost strategies to improve airway clearance and cough augmentation in ALS patients is the breath-stacking technique; in this technique, a manual resuscitation bag with a one-way valve is used to deliver a large breath volume to the patient's lungs [63].

The manual assist technique is another cough assist technique for ALS patients, which requires a trained person to apply pressure on the patient's chest with one forearm while the other hand thrust on the abdomen during expiration [124].

Neurodegenerative disease also leads to difficulty in clearing secretions because of respiratory muscle weakness and bulbar insufficiency. High-frequency chest wall oscillation by using a wearable vest helps to mobilize secretions and decrease symptoms of breathlessness in these patients. In three studies, it was used twice a day for 10-30 minutes per session [125, 126]. If secretions are tenacious or purulent, chest physiotherapy with percussion could be useful [127].

Mechanical Insufflation-Exsufflation (MI-E) is a therapy designed to generate effective expiratory flow rates in medically stable patients with bulbar and nonbulbar ALS [128]. The recommended initial MI-E settings typically include an inspiratory pressure of +40 cm H2O and an expiratory pressure of -40 cm H2O. However, adjustments may be required based on individual patient factors, such as height and lung capacity, to minimize the risk of complications, including pneumothorax [129].

Invasive Ventilation

Individuals who experience bulbar dysfunction and excessive sialorrhea may not tolerate non-invasive ventilation [27]. In situations where non-invasive ventilation is not well-tolerated or becomes insufficient due to advancing weakness of the respiratory muscles, an alternative option is invasive ventilation, specifically tracheostomy. This involves the insertion of a tube into the lower respiratory tract to provide assisted breathing support [130, 131]. It is also performed in patients on continuous NIV for more than 18 hours per day [132].

Tracheostomy provides better ventilator pressure and gas exchange due to less air leakage in comparison with NIV. However, it can lead to a decline in patients' physical function and significantly increase the burden on caregivers [133, 134]. 70% of patients experience loss of swallowing and limb function after tracheostomy [135]. There is a marked difference in the prevalence of tracheostomy in different geographic regions, even within areas of the same country [132]. One explanation for this variation is social, cultural, and religious differences, which affect the decision-making process for introducing tracheostomy [136].

The decision to stop tracheostomy varies among different countries, but mostly it is legal [137].

Among the various respiratory treatments for ALS, there is an experimental strategy called acute intermittent hypoxia. This method involves repeated brief reductions in inspired oxygen levels (~9–10% oxygen) for 60 to 90 seconds, separated by intervals of normoxia (21% oxygen) for 1-2 minutes. It may have the potential to preserve breathing function in ALS patients [138]. Overall, effective management of respiratory complications in ALS is vital for improving patient outcomes and quality of life. Integrating treatments such as non-invasive ventilation (NIV), cough-assist techniques, strength training, and, when indicated, invasive ventilation should be considered an essential part of comprehensive care for these patients. Table-5 summarizes respiratory therapy management strategies.

Challenges and Barriers to Rehabilitation Interventions for ALS

Patients Factors

Rehabilitation interventions pose various challenges for individuals with ALS. One of the most challenging issues for patients dealing with ALS is financial constraints because the cost of rehabilitation services, assistive devices, and medications can be a significant barrier for them; as Henschke et al. indicated in their study, many ALS patients in Germany commonly face issues with the availability and financing of assistive devices [139].

Another obstacle arises for ALS patients residing in remote and rural areas who face difficulty accessing well-equipped multidisciplinary clinics. Additionally, although technological advancements in ALS rehabilitation a good news, it is important to consider that some patients, particularly the elderly, may encounter challenges in adapting to certain technologies, so they need additional time for learning.

Caregiver Factors

Primary caregivers for patients with ALS are usually family members who face many challenges. The most common challenge for them has been reported travel and the cost of treatments. As a previous study indicated, in addition to the stress of leaving a family member, caregivers also grapple with the fear of depleting their savings on medical expenses [140].

Many of them find it difficult to balance their time with their caregiving responsibilities, also they may suffer from psychosocial distress [141]. Caregivers neglect their own needs to take care of the person with ALS, which can threaten their well-being [142]. A study demonstrated that increased behavioral and physical impairment in ALS patients is linked to a higher prevalence of depressive feelings among caregivers [143].

Healthcare System Factors

A multidisciplinary team for patients with ALS consists of a physiatrist, neurologist, gastroenterologist, social worker, occupational therapist, speech therapist, pulmonologist, nurse, physiatrist, dietitian, and psychologist [144]. To achieve the optimum results from rehabilitation, comprehensive and coordinated care among these specialists and health care is needed, so lack of integration of care across different providers can be challenging [145].

Another healthcare barrier that hinders effective ALS rehabilitation is that limited awareness and understanding of ALS among healthcare professionals may cause delays in diagnosis and inadequate referrals to rehabilitation services [146]. It appears that more than half of the patients received alternative diagnoses rather than a confirmed diagnosis of ALS [147]. Thus, ongoing education and training for healthcare providers are essential to improve ALS care and rehabilitation.

One of the restrictions of healthcare systems for the rehabilitation of ALS patients is that they may face difficulties in terms of resources, including the availability of specialized equipment, assistive devices, and access to rehabilitation facilities. Also, Insurance coverage can limit ALS patients' ability to access needed rehabilitation interventions, assistive technologies, and support services.

It's important to consider that these barriers and challenges can vary across different regions.

Conclusion

Currently, since there is no cure-all for ALS, treatment mainly targets managing symptoms. Yet, certain therapies show promise in slowing its progression and potentially enhancing survival rates. ALS profoundly affects individuals, significantly impairing motor abilities, communication, and sometimes even nutrition and breathing. This makes rehabilitation a critical part of all-encompassing care for those afflicted.

In our paper, we've aimed to explore various rehabilitation aspects for ALS patients. However, it's clear that research in this area is lacking, and there's a noticeable absence of comprehensive guidelines.

Future efforts need to focus on developing groundbreaking rehab strategies and fostering stronger teamwork across various medical disciplines. As research progresses, we anticipate the ALS rehabilitation field will evolve, offering enhanced support to patients and their families.

Acknowledgments

The authors would like to express their gratitude to Dr. Amirreza Manteghinejad for his valuable feedback during the writing and revision stages of this manuscript.

Conflicts of Interest

There is nothing to declare.

GMJ Copyright© 2025, Galen Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) Email:gmj@salviapub.com

 Correspondence to: Maryam Behroozinia, Department of Physical Medicine and Rehabilitation, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Telephone Number: 031334455051 Email Address: maryambehroozynia@yahoo.com

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Table 1. Revised El Escorial Criteria for diagnosis of ALS
A-Criteria	Clinical, electrophysiological, or neuropathological evidence of LMN degeneration Clinical evidence of UMN degeneration. Progressive spread of symptoms beyond typical nerve supply areas.
B-Criteria	The absence of findings typical of other diseases that could explain the observed symptoms.

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Table 2. Diagnostic classifications of ALS based on the Awaji-Shima consensus
Clinically definite ALS	clinical or electrophysiological evidence by the presence of LMN as well as UMN signs in the bulbar region and at least two spinal regions or the presence of LMN and UMN signs in three spinal regions
Clinically probable ALS	clinical or electrophysiological evidence by LMN and UMN signs in at least two regions with some UMN signs necessarily rostral to (above) the LMN signs
Clinically possible ALS	clinical or electrophysiological signs of UMN and LMN dysfunction are found in only one region or UMN signs are found alone in two or more regions or LMN signs are found rostral to UMN signs

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Table 3. Summary of Key Recommendations for Physical Therapy in ALS.
Recommendations	Type of exercise
Perform 1-2 sessions of active and passive ROM exercises daily for every patient.	ROM exercise
Done daily at the beginning of the disease	Stretching exercise
Begin muscle strengthening exercises immediately after diagnosis Mild to moderate level of intensity Exercise modification should be considered when muscle soreness and fatigue last for more than 30 minutes.	Strengthening Exercises
To increase muscle strength: High load and low-speed To increase muscle endurance: Low load and high-speed	RMT (encompassing IMT and RMT)

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Table 4. Summary of Key Recommendations for the Management of Dysphagia

Dietary modification, including soft, semi-solid, and semi-liquid foods and regulating bolus sizes

Swallowing techniques such as supraglottic swallow and chin-tuck maneuver

High-energy supplementations

Feeding tube placement when: body weight exceeding 5%–10% of an individual’s typical weight BMI <20 kg/m² dysphagia Feeding tube options include: Nasogastric tube: Suitable for short-term use. PEG: Recommended before FVC decreases to 50% of the predicted value. PRG: Indicated for patients with respiratory failure, particularly those with an FVC of less than 50%.

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Table 5. Summary of Key Recommendations for the Management of Respiratory Care in ALS
Cough Assist Techniques	Breath-stacking technique Manual assist technique High-frequency chest wall oscillation Mechanical Insufflation-Exsufflation
NIV	Indication: Maximum inspiratory pressure ≤ 60 cm H2O, Spo2≤ 88% for at least five continuous minutes Paco2> 45 mm Hg Symptoms related to hypercapnia
NIPPV	Indication: FVC is less than 50% of the predicted value Titration: Starting at 8 cm of H20 IPAP and 4 cm of H20 EPAP
Invasive Ventilation	Indication: When NIV is not well-tolerated NIV for more than 18 hours per day

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References

1. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377(2):162-72.
2. Cunha-Oliveira T, Montezinho L, Mendes C, Firuzi O, Saso L, Oliveira PJ, et al. Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention. Oxid Med Cell Longev. 2020;2020:5021694.
3. van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, et al. Amyotrophic lateral sclerosis. Lancet. 2017;390(10107):2084-98.
4. Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2019;710:132933.
5. Cruz MP. Edaravone (Radicava): A Novel Neuroprotective Agent for the Treatment of Amyotrophic Lateral Sclerosis. P T. 2018;43(1):25-8.
6. Soriani MH, Desnuelle C. Care management in amyotrophic lateral sclerosis. Rev Neurol (Paris). 2017;173(5):288-99.
7. Obrador E, Salvador R, López-Blanch R, Jihad-Jebbar A, Vallés SL, Estrela JM. Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis. Antioxidants (Basel). 2020;9(9):901.
8. Tard C, Defebvre L, Moreau C, Devos D, Danel-Brunaud V. Clinical features of amyotrophic lateral sclerosis and their prognostic value. Rev Neurol (Paris). 2017;173(5):263-72.
9. Gamskjaer T, Werlauff U, Handberg C. Investigating job satisfaction in palliative rehabilitation: Reflections and perspectives of health professionals working with amyotrophic lateral sclerosis. J Eval Clin Pract. 2022;28(1):108-19.
10. Chio A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009;10(5-6):310-23.
11. Silva JPR, Júnior JBS, Dos Santos EL, de Carvalho FO, de França Costa IMP, de Mendonça DMF. Quality of life and functional independence in amyotrophic lateral sclerosis: A systematic review. Neurosci Biobehav Rev. 2020;111:1-11.
12. Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1(5):293-9.
13. De Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008;119(3):497-503.
14. Byrne S, Walsh C, Lynch C, Bede P, Elamin M, Kenna K, et al. Rate of familial amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82(6):623-7.
15. Battaglia G, Bruno V. Metabotropic glutamate receptor involvement in the pathophysiology of amyotrophic lateral sclerosis: new potential drug targets for therapeutic applications. Curr Opin Pharmacol. 2018;38:65-71.
16. Zarei S, Carr K, Reiley L, Diaz K, Guerra O, Altamirano PF, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171.
17. Ingre C, Roos PM, Piehl F, Kamel F, Fang F. Risk factors for amyotrophic lateral sclerosis. Clin Epidemiol. 2015:181-93.
18. Pupillo E, Poloni M, Bianchi E, Giussani G, Logroscino G, Zoccolella S, et al. Trauma and amyotrophic lateral sclerosis: a european population-based case-control study from the EURALS consortium. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19(1-2):118-25.
19. Logan R, Dubel-Haag J, Schcolnicov N, Miller SJ. Novel genetic signatures associated with sporadic amyotrophic lateral sclerosis. Front Genet. 2022;13:851496.
20. Chia R, Chio A, Traynor BJ. Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications. Lancet Neurol. 2018;17(1):94-102.
21. Duffy JR, Peach RK, Strand EA. Progressive apraxia of speech as a sign of motor neuron disease. AJA. 2007;16(3):198-208.
22. Kuwabara S, Sonoo M, Komori T, Shimizu T, Hirashima F, Inaba A, et al. Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity. Muscle Nerve. 2008;37(4):426-30.
23. Riad SM, Hathout H, Huang JC. High T2 signal in primary lateral sclerosis supports the topographic distribution of fibers in the corpus callosum: assessing disease in the primary motor segment. AJNR Am J Neuroradiol. 2011;32(4):E61-4.
24. Masrori P, Van Damme P. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol. 2020;27(10):1918-29.
25. Ajroud-Driss S, Siddique T. Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta. 2015;1852(4):679-84.
26. Ferguson TA, Elman LB. Clinical presentation and diagnosis of amyotrophic lateral sclerosis. NeuroRehabilitation. 2007;22(6):409-16.
27. Leigh PN, Abrahams S, Al-Chalabi A, Ampong MA, Goldstein LH, Johnson J, et al. The management of motor neurone disease. J Neurol Neurosurg Psychiatry. 2003;74 Suppl 4(Suppl 4):iv32-iv47.
28. Rabinstein AA, Wijdicks EF. Warning signs of imminent respiratory failure in neurological patients. Semin Neurol. 2003;23(1):97-104.
29. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942-55.
30. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124(Pt 9):1708-19.
31. Garuti G, Rao F, Ribuffo V, Sansone VA. Sialorrhea in patients with ALS: current treatment options. Degener Neurol Neuromuscul Dis. 2019;9:19-26.
32. Danel-Brunaud V, Touzet L, Chevalier L, Moreau C, Devos D, Vandoolaeghe S, et al. Ethical considerations and palliative care in patients with amyotrophic lateral sclerosis: a review. Rev Neurol (Paris). 2017;173(5):300-7.
33. Elamin M, Phukan J, Bede P, Jordan N, Byrne S, Pender N, et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology. 2011;76(14):1263-9.
34. Dorst J, Ludolph AC, Huebers A. Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis. Ther Adv Neurol Disord. 2018;11:1756285617734734.
35. Ilieva H, Vullaganti M, Kwan J. Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis. Bmj. 2023;383:e075037.
36. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;2012(3):CD001447.
37. Deng Y, Xu Z, Xu B, Tian Y, Xin X, Deng X, et al. The protective effect of riluzole on manganese caused disruption of glutamate-glutamine cycle in rats. Brain Res. 2009;1289:106-17.
38. Bensimon G, Lacomblez L, Delumeau JC, Bejuit R, Truffinet P, Meininger V, et al. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J Neurol. 2002;249(5):609-15.
39. Tzeplaeff L, Wilfling S, Requardt MV, Herdick M. Current State and Future Directions in the Therapy of ALS. Cells. 2023;12(11):1523.
40. Schultz J. Disease-modifying treatment of amyotrophic lateral sclerosis. Am J Manag Care. 2018;24(15 Suppl):S327-S35.
41. Lejman J, Panuciak K, Nowicka E, Mastalerczyk A, Wojciechowska K, Lejman M. Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives. Int J Mol Sci. 2023;24(2):1130.
42. de Carvalho M, Nogueira A, Pinto A, Miguens J, Sales Luis ML. Reflex sympathetic dystrophy associated with amyotrophic lateral sclerosis. J Neurol Sci. 1999;169(1-2):80-3.
43. Assouline A, Levy A, Abdelnour-Mallet M, Gonzalez-Bermejo J, Lenglet T, Le Forestier N, et al. Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients. Int J Radiat Oncol Biol Phys. 2014;88(3):589-95.
44. Moore DH, Miller RG. Improving efficiency of ALS clinical trials using lead-in designs. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004; 5: 57-60.
45. White LJ, Dressendorfer RH. Exercise and multiple sclerosis. Sports Med. 2004;34(15):1077-100.
46. Majmudar S, Wu J, Paganoni S. Rehabilitation in amyotrophic lateral sclerosis: why it matters. Muscle Nerve. 2014;50(1):4-13.
47. Karam CY, Paganoni S, Joyce N, Carter GT, Bedlack R. Palliative Care Issues in Amyotrophic Lateral Sclerosis: An Evidenced-Based Review. Am J Hosp Palliat Care. 2016;33(1):84-92.
48. Medicine ACoS. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc. 1998;30:975-91.
49. Tsitkanou S, Della Gatta P, Foletta V, Russell A. The role of exercise as a non-pharmacological therapeutic approach for amyotrophic lateral sclerosis: beneficial or detrimental? Front Neurol. 2019;10:783.
50. Clawson LL, Cudkowicz M, Krivickas L, Brooks BR, Sanjak M, Allred P, et al. A randomized controlled trial of resistance and endurance exercise in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19(3-4):250-8.
51. Kato N, Hashida G, Konaka K. Effect of muscle strengthening exercise and time since onset in patients with amyotrophic lateral sclerosis: A 2-patient case series study. Medicine (Baltimore). 2018;97(25):e11145.
52. Psalidas CP, Kottaras A, Lytras D, Iakovidis P, Leptourgos G, Moutaftsis K. The role of therapeutic exercise as a means of intervention for the treatment of amyotrophic lateral sclerosis. Int J Adv Community Med. 2021;4(2):29-31.
53. Strickland D, Smith SA, Dolliff G, Goldman L, Roelofs RI. Physical activity, trauma, and ALS: a case-control study. Acta Neurol Scand. 1996;94(1):45-50.
54. Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology. 1999;52(7):1311-23.
55. Harwood CA, McDermott CJ, Shaw PJ. Physical activity as an exogenous risk factor in motor neuron disease (MND): a review of the evidence. Amyotroph Lateral Scler. 2009;10(4):191-204.
56. Harwood CA, Westgate K, Gunstone S, Brage S, Wareham NJ, McDermott CJ, et al. Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis? Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(5-6):377-84.
57. Krivickas LS. Rehabilitation of Amyotrophic Lateral Sclerosis. Motor Neuron Disease. 2008:31.
58. Gruis KL, Lechtzin N. Respiratory therapies for amyotrophic lateral sclerosis: a primer. Muscle Nerve. 2012;46(3):313-31.
59. Miller RG, Brooks BR, Swain-Eng RJ, Basner RC, Carter GT, Casey P, et al. Quality improvement in neurology: amyotrophic lateral sclerosis quality measures: report of the quality measurement and reporting subcommittee of the American Academy of Neurology. Neurology. 2013;81(24):2136-40.
60. Niedermeyer S, Murn M, Choi PJ. Respiratory Failure in Amyotrophic Lateral Sclerosis. Chest. 2019;155(2):401-8.
61. Ferreira GD, Costa AC, Plentz RD, Coronel CC, Sbruzzi G. Respiratory training improved ventilatory function and respiratory muscle strength in patients with multiple sclerosis and lateral amyotrophic sclerosis: systematic review and meta-analysis. Physiotherapy. 2016;102(3):221-8.
62. Plowman EK, Tabor-Gray L, Rosado KM, Vasilopoulos T, Robison R, Chapin JL, et al. Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial. Muscle Nerve. 2019;59(1):40-6.
63. Rafiq MK, Bradburn M, Proctor AR, Billings CG, Bianchi S, McDermott CJ, et al. A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(7-8):448-55.
64. Tzelepis GE, Vega DL, Cohen ME, Fulambarker AM, Patel KK, McCool FD. Pressure-flow specificity of inspiratory muscle training. J Appl Physiol (1985). 1994;77(2):795-801.
65. Tzelepis GE, Kadas V, McCool FD. Inspiratory muscle adaptations following pressure or flow training in humans. Eur J Appl Physiol Occup Physiol. 1999;79(6):467-71.
66. Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, et al. Respiratory muscle training in children and adults with neuromuscular disease. Cochrane Database Syst Rev. 2019;9(9):CD011711.
67. Cabrita B, Dias S, Fernandes AL, Correia S, Ferreira J, Simao P. Inspiratory muscle training in neuromuscular patients: Assessing the benefits of a novel protocol. J Back Musculoskelet Rehabil. 2021;34(4):537-43.
68. Vicente-Campos D, Sanchez-Jorge S, Chicharro JL, Becerro-de Bengoa-Vallejo R, Rodriguez-Sanz D, Garcia AR, et al. POWERbreathe((R)) Inspiratory Muscle Training in Amyotrophic Lateral Sclerosis. J Clin Med. 2022;11(22):6655.
69. Dubbioso R, Spisto M, Hausdorff JM, Aceto G, Iuzzolino VV, Senerchia G, et al. Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis. Eur J Neurol. 2023;30(10):3056-67.
70. Lange DJ, Murphy PL, Maxfield RA, Skarvala A-M, Riedel G. Management of patients with amyotrophic lateral sclerosis. J Neurol Rehabil. 1994;8(2):75-82.
71. Creemers H, Beelen A, Grupstra H, Nollet F, van den Berg LH. The provision of assistive devices and home adaptations to patients with ALS in the Netherlands: patients' perspectives. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5-6):420-5.
72. Boostani R, Olfati N, Shamshiri H, Salimi Z, Fatehi F, Hedjazi SA, et al. Iranian clinical practice guideline for amyotrophic lateral sclerosis. Front Neurol. 2023;14:1154579.
73. Lindenberger E, Meier DE. What Special Considerations Are Needed for Individuals With Amyotrophic Lateral Sclerosis, Multiple Sclerosis, or Parkinson Disease? Evidence-Based Practice in Palliative Medicine. 2013:317-29.
74. Lou JS, Reeves A, Benice T, Sexton G. Fatigue and depression are associated with poor quality of life in ALS. Neurology. 2003;60(1):122-3.
75. Fateh HR, Askary-Kachoosangy R, Shirzad N, Akbarzadeh-Baghban A, Fatehi F. The effect of energy conservation strategies on fatigue, function, and quality of life in adults with motor neuron disease: Randomized controlled trial. Curr J Neurol. 2022;21(2):83-90.
76. Kos D, Duportail M, Meirte J, Meeus M, D'Hooghe M B, Nagels G, et al. The effectiveness of a self-management occupational therapy intervention on activity performance in individuals with multiple sclerosis-related fatigue: a randomized-controlled trial. Int J Rehabil Res. 2016;39(3):255-62.
77. Vanage SM, Gilbertson KK, Mathiowetz V. Effects of an energy conservation course on fatigue impact for persons with progressive multiple sclerosis. Am J Occup Ther. 2003;57(3):315-23.
78. Mathiowetz VG, Matuska KM, Finlayson ML, Luo P, Chen HY. One-year follow-up to a randomized controlled trial of an energy conservation course for persons with multiple sclerosis. Int J Rehabil Res. 2007;30(4):305-13.
79. Matuska K, Mathiowetz V, Finlayson M. Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue. Am J Occup Ther. 2007;61(1):62-9.
80. Lewis M, Rushanan S. The role of physical therapy and occupational therapy in the treatment of amyotrophic lateral sclerosis. NeuroRehabilitation. 2007;22(6):451-61.
81. Ball L, Beukelman D, Bardach L. AAC intervention for ALS Paul H. Brookes Baltimore. 2007; 43(6):841-78.
82. Yorkston KM, Beukelman DR, Strand EA, Hakel M. Management of motor speech disorders in children and adults. Pro-ed Austin: TX; 1999.
83. Beukelman DR, Garrett KL, Yorkston KM. Augmentative communication strategies for adults with acute or chronic medical conditions. Brookes: Pub; 2007.
84. Tomik B, Guiloff RJ. Dysarthria in amyotrophic lateral sclerosis: A review. Amyotroph Lateral Scler. 2010;11(1-2):4-15.
85. Pugliese R, Sala R, Regondi S, Beltrami B, Lunetta C. Emerging technologies for management of patients with amyotrophic lateral sclerosis: from telehealth to assistive robotics and neural interfaces. J Neurol. 2022;269(6):2910-21.
86. Murphy J. Communication strategies of people with ALS and their partners. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5(2):121-6.
87. Beukelman D, Fager S, Nordness A. Communication support for people with ALS. Neurol Res Int. 2011;2011:714693.
88. Gelinas D, Miller R. A treatable disease: a guide to the management of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis London: Martin Dunitz. 2000:405-22.
89. Bongioanni P. Communication impairment in. ALS patients assessment and treatment: Citeseer; 2012.
90. Linse K, Aust E, Joos M, Hermann A. Communication matters—pitfalls and promise of hightech communication devices in palliative care of severely physically disabled patients with amyotrophic lateral sclerosis. Front Neurol. 2018;9:603.
91. Clerc M, Mattout J, Maby E, Devlaminck D, Papadopoulo T, Guy V, et al. Verbal communication through brain computer interfaces. Interspeech-14th Annual Conference of the International Speech Communication Association-2013. 2013; :00842851.
92. Guy V, Soriani M-H, Bruno M, Papadopoulo T, Desnuelle C, Clerc M. Brain computer interface with the P300 speller: Usability for disabled people with amyotrophic lateral sclerosis. Ann Phys Rehabil Med. 2018;61(1):5-11.
93. Edughele HO, Zhang Y, Muhammad-Sukki F, Vien Q-T, Morris-Cafiero H, Agyeman MO. Eye-tracking assistive technologies for individuals with amyotrophic lateral sclerosis. IEEE Access. 2022;10:41952-72.
94. Calvo A, Chiò A, Castellina E, Corno F, Farinetti L, Ghiglione P, et al. Eye tracking impact on quality-of-life of ALS patients Computers Helping People with Special Needs: 11th International Conference, ICCHP 2008, Linz, Austria, July 9-11, 2008 Proceedings 11. Springer. 2008; :70-78.
95. Cipresso P, Meriggi P, Carelli L, Solca F, Meazzi D, Poletti B, et al. The combined use of Brain Computer Interface and Eye-Tracking technology for cognitive assessment in Amyotrophic Lateral Sclerosis 2011 5th International conference on pervasive computing technologies for healthcare (PervasiveHealth) and workshops. IEEE. 2011; : 320-324.
96. Ball LJ, Nordness AS, Fager SK, Kersch K, Mohr B, Pattee GL, et al. Eye gaze access of AAC technology for people with amyotrophic lateral sclerosis. J Med Speech-Lang Pathol. 2010;18(3):11.
97. Paganoni S, Karam C, Joyce N, Bedlack R, Carter GT. Comprehensive rehabilitative care across the spectrum of amyotrophic lateral sclerosis. NeuroRehabilitation. 2015;37(1):53-68.
98. Tabor L, Gaziano J, Watts S, Robison R, Plowman EK. Defining Swallowing-Related Quality of Life Profiles in Individuals with Amyotrophic Lateral Sclerosis. Dysphagia. 2016;31(3):376-82.
99. Printza A, Boziki M, Triaridis S, Kiousi V, Arnaoutoglou M, Constantinidis J, et al. Tongue strength, dysphagia questionnaire, pharyngeal secretions and FEES findings in dysphagia management in amyotrophic lateral sclerosis. Auris Nasus Larynx. 2021;48(4):672-82.
100. Muscaritoli M, Kushta I, Molfino A, Inghilleri M, Sabatelli M, Rossi Fanelli F. Nutritional and metabolic support in patients with amyotrophic lateral sclerosis. Nutrition. 2012;28(10):959-66.
101. Palovcak M, Mancinelli JM, Elman LB, McCluskey L. Diagnostic and therapeutic methods in the management of dysphagia in the ALS population: issues in efficacy for the out-patient setting. NeuroRehabilitation. 2007;22(6):417-23.
102. Dorst J, Cypionka J, Ludolph AC. High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: a prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(7-8):533-6.
103. Greenwood DI. Nutrition management of amyotrophic lateral sclerosis. Nutr Clin Pract. 2013;28(3):392-9.
104. Verschueren A, Monnier A, Attarian S, Lardillier D, Pouget J. Enteral and parenteral nutrition in the later stages of ALS: an observational study. Amyotroph Lateral Scler. 2009;10(1):42-6.
105. Scott AG, Austin HE. Nasogastric feeding in the management of severe dysphagia in motor neurone disease. Palliat Med. 1994;8(1):45-9.
106. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1218-26.
107. Park JH, Kang SW. Percutaneous radiologic gastrostomy in patients with amyotrophic lateral sclerosis on noninvasive ventilation. Arch Phys Med Rehabil. 2009;90(6):1026-9.
108. Stavroulakis T, Baird WO, Baxter SK, Walsh T, Shaw PJ, McDermott CJ. Factors influencing decision-making in relation to timing of gastrostomy insertion in patients with motor neurone disease. BMJ Support Palliat Care. 2014;4(1):57-63.
109. Shoesmith C. Palliative care principles in ALS. Handb Clin Neurol. 2023;191:139-55.
110. Diagnosis ETFo, Sclerosis: MoAL, Andersen PM, Abrahams S, Borasio GD, de Carvalho M, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)–revised report of an EFNS task force. Eur J Neurol. 2012;19(3):360-75.
111. Hess DR. Noninvasive ventilation in neuromuscular disease: equipment and application. Respir Care. 2006;51(8):896-911.
112. Bourke S, Bullock R, Williams T, Shaw P, Gibson G. Noninvasive ventilation in ALS: indications and effect on quality of life. Neurology. 2003;61(2):171-7.
113. Mustfa N, Walsh E, Bryant V, Lyall R, Addington-Hall J, Goldstein L, et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology. 2006;66(8):1211-7.
114. Georges M, Morelot-Panzini C, Similowski T, Gonzalez-Bermejo J. Noninvasive ventilation reduces energy expenditure in amyotrophic lateral sclerosis. BMC Pulm Med. 2014;14(1):17.
115. Goldberg A. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation--a. Chest. 1999;116(2):521.
116. Vrijsen B, Testelmans D, Belge C, Vanpee G, Van Damme P, Buyse B. Patient-ventilator asynchrony, leaks and sleep in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(5-6):343-50.
117. Antonelli M, Conti G, Pelosi P, Gregoretti C, Pennisi MA, Costa R, et al. New treatment of acute hypoxemic respiratory failure: noninvasive pressure support ventilation delivered by helmet--a pilot controlled trial. Crit Care Med. 2002;30(3):602-8.
118. Fiorentino G, Annunziata A, Gaeta AM, Lanza M, Esquinas A. Continuous noninvasive ventilation for respiratory failure in patients with amyotrophic lateral sclerosis: current perspectives. Degener Neurol Neuromuscul Dis. 2018;8:55-61.
119. Everett EA, Pedowitz E, Maiser S, Cohen J, Besbris J, Mehta AK, et al. Top ten tips palliative care clinicians should know about amyotrophic lateral sclerosis. J Palliat Med. 2020;23(6):842-7.
120. Kim HS, Woo H, Choi SJ, Baek JG, Ryu JS, Shin HI, et al. Factors associated with adherence to noninvasive positive pressure ventilation in amyotrophic lateral sclerosis. PLoS One. 2024;19(5):e0302515.
121. Melo J, Homma A, Iturriaga E, Frierson L, Amato A, Anzueto A, et al. Pulmonary evaluation and prevalence of non-invasive ventilation in patients with amyotrophic lateral sclerosis: a multicenter survey and proposal of a pulmonary protocol. J Neurol Sci.. 1999;169(1-2):114-7.
122. Pinto S, De Carvalho M. Is a four-hour use of non-invasive ventilation enough to define compliance? Amyotroph Lateral Scler . 2010;11(1-2):250-2.
123. Hadjikoutis S, Wiles C, Eccles R. Cough in motor neuron disease: a review of mechanisms. Qjm. 1999;92(9):487-94.
124. McHenry KL. Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis. Respir Care. 2024;69(2):227-37.
125. Jones U, Enright S, Busse M. Management of respiratory problems in people with neurodegenerative conditions: a narrative review. Physiotherapy. 2012;98(1):1-12.
126. Lange D, Lechtzin N, Davey C, David W, Heiman-Patterson T, Gelinas D, et al. High-frequency chest wall oscillation in ALS: an exploratory randomized, controlled trial. Neurology. 2006;67(6):991-7.
127. Ambrosino N, Carpene N, Gherardi M. Chronic respiratory care for neuromuscular diseases in adults. Eur Respir J. 2009;34(2):444-51.
128. Sancho J, Servera E, Díaz J, Marín J. Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis. Chest. 2004;125(4):1400-5.
129. Funo K, Negishi Y, Akamine C, Takeuchi R, Uzawa Y. Setting Mechanical Insufflation-Exsufflation (MI-E) Pressures for Amyotrophic Lateral Sclerosis (ALS) Patients to Improve Atelectasis and Reduce Risk of Pneumothorax: A Case Report. Cureus. 2022;14(6):e25786.
130. Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN, et al. Good practice in the management of amyotrophic lateral sclerosis: clinical guidelines An evidence-based review with good practice points EALSC Working Group. Amyotroph Lateral Scler. 2007;8(4):195-213.
131. Morris LL, Whitmer A, McIntosh E. Tracheostomy care and complications in the intensive care unit. Crit Care Nurse. 2013;33(5):18-30.
132. Spataro R, Bono V, Marchese S, La Bella V. Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis. J Neurol Sci. 2012;323(1-2):66-70.
133. Magelssen M, Holmoy T, Horn MA, Fondenaes OA, Dybwik K, Forde R. Ethical challenges in tracheostomy-assisted ventilation in amyotrophic lateral sclerosis. J Neurol. 2018;265(11):2730-6.
134. Hayashi N, Atsuta N, Yokoi D, Nakamura R, Nakatochi M, Katsuno M, et al. Prognosis of amyotrophic lateral sclerosis patients undergoing tracheostomy invasive ventilation therapy in Japan. J Neurol Neurosurg Psychiatry. 2020;91(3):285-90.
135. Kimura F. [Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis]. Rinsho Shinkeigaku. 2016;56(4):241-7.
136. Vianello A, Concas A. Tracheostomy ventilation in ALS: a Japanese bias. J Neurol Sci. 2014;344(1):3-4.
137. Turner MR, Faull C, McDermott CJ, Nickol AH, Palmer J, Talbot K. Tracheostomy in motor neurone disease. Pract Neurol. 2019;19(6):467-75.
138. Sales de Campos P, Olsen WL, Wymer JP, Smith BK. Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review. Chron Respir Dis. 2023;20:14799731231175915.
139. Henschke C. Provision and financing of assistive technology devices in Germany: A bureaucratic odyssey The case of amyotrophic lateral sclerosis and Duchenne muscular dystrophy. Health policy. 2012;105(2-3):176-84.
140. Brizzi KT, Bridges JFP, Yersak J, Balas C, Thakur N, Galvin M, et al. Understanding the needs of people with ALS: a national survey of patients and caregivers. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(5-6):355-63.
141. Olesen LK, la Cour K, With H, Mahoney AF, Handberg C. A cross-sectional evaluation of acceptability of an online palliative rehabilitation program for family caregivers of people with amyotrophic lateral sclerosis and cognitive and behavioral impairments. BMC Health Serv Res. 2022;22(1):697.
142. Olesen LK, la Cour K, With H, Handberg C. Reflections of family caregivers and health professionals on the everyday challenges of caring for persons with amyotrophic lateral sclerosis and cognitive impairments: a qualitative study. Palliat Care Soc Pract. 2022;16:26323524221077702.
143. de Wit J, Bakker LA, van Groenestijn AC, van den Berg LH, Schröder CD, Visser-Meily JM, et al. Caregiver burden in amyotrophic lateral sclerosis: a systematic review. Palliat Med. 2018;32(1):231-45.
144. Miller R, Jackson C, Kasarskis E, England J, Forshew D, Johnston W, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1227-33.
145. Aoun SM, Connors SL, Priddis L, Breen LJ, Colyer S. Motor Neurone Disease family carers' experiences of caring, palliative care and bereavement: an exploratory qualitative study. Palliat Med. 2012;26(6):842-50.
146. Hogden A, Foley G, Henderson RD, James N, Aoun SM. Amyotrophic lateral sclerosis: improving care with a multidisciplinary approach. J Multidiscip Healthc. 2017; 10: 205-15.
147. Paganoni S, Macklin EA, Lee A, Murphy A, Chang J, Zipf A, et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5-6):453-6.

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