Posted: March 7th, 2024

Neurodegeneration: The Efficacy of the Thermal Rehabilitation Approach

Neurodegeneration: The Efficacy of the Thermal Rehabilitation Approach
1. Introduction
The introduction provides a definition of neurodegeneration and highlights the importance of rehabilitation in these conditions. It also introduces the thermal rehabilitation approach. There has been an increasing interest in the application of more sophisticated technologies to make rehabilitation strategies more efficient. Modern computer-based methods allow for the objective measurements and can parametrize the level of impairment with respect to the type and the stage of the disease. Such technology means rehabilitation may be performed in more home-like environments, when coupled with robotics, can be administered by the machines. These techniques also allow for the personalization of treatments to the pathology of the individual patient which has a potential to significantly improve the patient welfare. On the other hand, the traditional rehabilitation methods follow a trial and error approach due to the lack of the objective tools and a low level of the data produced. Even though patients are subjected to assessments, on which the therapy programs are based, frequently a successful rehabilitation cannot be guaranteed because such subjective viewpoints may not reflect the patient’s needs in the process of the ability and the recovery. Therefore, many specialists in the field of the rehabilitation engineering, including the authors, are working on the development of the advanced computational methods. In fact, not the single modern rehabilitation technology, but a combination of the different method may hold the key for the better understanding of the recovery process and the more successful treatments. The wider application of these novel approaches, however, still requires the advance in the information technology together with the necessary adjustments in the conventional rehabilitation education as well as towards the implementation of the legal acts that will allow for the dissemination of the computational methods in the broader, clinical profession.
1.1. Definition of Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Put simply, a neuron is the basic building block of the nervous system, which includes the brain and spinal cord. Neurons, which look like tree branches reaching out from the main part of the cell, transmit information electrically and chemically to other cells. The structure of a neuron normally keeps it healthy, assisting it to transmit information. However, many neurodegenerative diseases affect people because the function of a gene leads to the abnormal cell proteins that cause cells to be destroyed. This might occur due to toxic substances being produced in the neuron (as in MND) or the abnormal proteins which may result from a mix of genetic errors and environmental factors (as in Alzheimer’s disease). Many neurodegenerative diseases, like Alzheimer’s and Parkinson’s, occur as a result of ageing. However, some, like Huntington’s disease, are caused by a genetic fault and occur at a much earlier age. There are also other conditions called ‘spinocerebellar ataxias’ which, though rare, can affect people in early adulthood. The effects of neurodegenerative diseases can range from loss of bladder control or eyesight to the complete inability to move and breathe independently. Such diseases can have a massive impact on lifestyle and life expectancy. For example, the average life expectancy for a person with MND is 14 months from diagnosis. With diseases like Parkinson’s where there is no cure and symptoms continually worsen, there is a similar decrease in quality of life; however, the time of progression is often much longer. It is for these reasons that many researchers have investigated the possibilities of different types of rehabilitation in order to slow down the effects of these diseases. Such treatments can range from physiotherapy, which focuses on using physical methods such as massage, heat treatments and exercise, to occupational therapy which can help people with a physical, sensory or cognitive disability to improve their ability to carry out everyday tasks. The main aim of these therapies is to help people to regain the highest level of function and independence as possible. Such treatments can range from physiotherapy, which focuses on using physical methods such as massage, heat treatments and exercise, to occupational therapy which can help people with a physical, sensory or cognitive disability to improve their ability to carry out everyday tasks. The main aim of these therapies is to help people to regain the highest level of function and independence as possible.
1.2. Importance of Rehabilitation in Neurodegenerative Diseases
It is beneficial to engage in therapy services when the disease is in its earlier stages so that the brain may learn to reroute messages around the areas that have been damaged. When the disease has advanced, routine physical and occupational therapy can continue to be beneficial by working to establish adapted modes of function. In cases of neurodegenerative diseases that are known to be terminal, therapy interventions may be aimed towards maintaining current abilities and making the individual as comfortable as possible.
The primary function of the brain is to direct or control the various movements and functions throughout the body. For all physical interventions in the rehabilitation process, the ultimate goal is to potentially enhance the body’s natural ability to repair and regenerate itself, the motivation behind physical therapy. The brain and the peripheral nervous system, which is composed of the nerves that branch out from the brain and spinal cord, can send communications to and from the rest of the body in order to direct activities and maintain movement. However, when any form of central nervous system insult—an injury or trauma to the brain, spinal cord, or nerves—occurs, benefits of rehabilitation services can become immediately clear. These interventions and the benefits they may bring to an individual are often governed by what is known as neuroplasticity, the brain’s ability to reorganize itself by forming new neural connections. However, the potentials of neuroplasticity can differ depending on the stage of the disease process.
The goals of rehabilitation for neurodegenerative diseases are to help individuals maintain the highest level of function, slow the progression of the disease, and improve overall well-being. Rehabilitation can take place in a variety of settings, such as outpatient therapy, inpatient rehabilitation hospitals, and long-term acute care facilities. Rehabilitation can also be administered on many different levels, including physical therapy, occupational therapy, and speech therapy. No matter the type or setting of rehabilitation, the primary focus is on an individualized approach aimed at providing the right help and support at the right times. Each treatment plan is highly tailored to the specific needs of the person in question.
1.3. Overview of Thermal Rehabilitation Approach
The therapeutic use of elevated environmental temperature has been described since ancient Greek and Roman times. In traditional saunas, the temperature is usually around 80-100°C, and elevated to 170-200°C in electric or infrared saunas, as opposed to the normal body temperature of 37°C. The main response to heat in humans is thermoregulatory, involving the autonomic and the hormonal systems. Skin’s blood vessels dilate when the skin becomes warmer and this is designed to facilitate heat dissipation and it also causes the “flush” appearance. In an extreme high temperature condition, such as that in a sauna, heart rate and the cardiac output will both increase in order to maintain an adequate circulation. However, the problem in traditional saunas is that humidity is usually high, and breathing hot air directly into the lungs can trigger breathing problems, particularly in patients with airway diseases, such as asthma. On the contrary to the dry heat in saunas, mud-bath therapy utilizes mainly the heat retention property of mud to cause a gradual increase of body temperature. Modulation of the water content and the compactness of mud can maintain the heat for a desired time, and this allows deeper penetration of heat into the body. Besides, it is also thought that the specific properties of the peloids themselves, as well as the associated bathing and dwell times, can individually modify the effects of mud-bath therapy. Patients may experience improvement of pain and joint stiffness in chronic rheumatic disorders, such as ankylosing spondylitis and rheumatoid arthritis, after a cycle of mud-bath therapy, which typically lasts for 2 to 3 weeks with 12 to 15 treatments. Despite the long history of the application, the clinical efficacy of thermal rehabilitation in various neurodegenerative disorders is questioned due to the lack of solid scientific evidence. The following content will explore the mechanisms of neurodegeneration, the neuroprotective effects of thermal therapy, and the physiological changes induced by thermal rehabilitation. Last but not least, a systematic review of the clinical trials, as well as the possible side effects and the safety concerns of using heat therapy as a neurorehabilitation option, will be discussed.
2. Theoretical Background
The nature of the brain from a biological and physical perspective has profound implications for the thermal rehabilitation approach that this article investigates. This section “Theoretical Background” serves as a bridge between the general concept of neurodegeneration with the topic of thermal rehabilitation and it provides a basic understanding of the nature of neurodegeneration illnesses and the rationale behind the thermal rehabilitation treatment. Neurodegeneration is the umbrella term for the progressive loss of structure or function of the neurons. It can lead to a myriad of diseases such as Alzheimer’s and Parkinson’s disease, and disease is often chronic, incurable and most importantly, it affects function of the parts of the body during the development of those diseases. The mechanisms behind neurodegeneration can be summarised by the concept of “positive feedback.” Under normal circumstances, the body’s self-regulating mechanisms will control the condition, however, under certain circumstances the system might work instably. When the cell is damaged, the body will try to repair the cell. However, in the case of neurodegeneration, most cells tend to die and every time a cell dies, it will release certain chemicals that will trigger a response of cell death and this process will keep going and the condition subsequently becomes worse and worse. Thermal therapy is the therapeutic approach that exploits this endogenous neuroprotective mechanism to prevent further damage and encourage cellular repair processes. The essence of the thermal therapy is to induce a mild increase in body temperature, leading to an elevation of functional capacity and increase of cellular metabolism. The rationale of thermal therapy is that all of the neurodegeneration diseases are temperature sensitive. For example, the core temperature difference between the cold environment and the warm environment will exacerbate certain kinds of symptoms in patients of multiple sclerosis, a typical neurodegeneration disease.
2.1. Mechanisms of Neurodegeneration
Neurodegeneration refers to the progressive loss of structure or function of neurons, including death of neurons. Most neurodegenerative diseases are characterized by the selective and gradual loss of neurons in specific regions of the central nervous system. The human nervous system is made up of diverse and complex types of neurons. These neurons can be mainly divided into two categories: neurons that continuously divide and neurons that do not divide because the functional significance of these divisions continues to remain speculative in adults. The neurons that do not divide are also called neurons that have “exited from the cell cycle”. It is found that the main feature of neurodegenerative diseases is the malfunction or death of particular populations of neurons, but not the continuous dividing neurons such as neural stem cells and progenitors. Over time, the brain’s processing ability can be increasingly impaired and the damage caused can’t be repaired. The progressive cell los
2.2. Neuroprotective Effects of Thermal Therapy
A recent study has shown that a specific type of HSP in rats can be increased after a course of sauna treatment. This is an exciting finding as it is a first evidence that thermal therapy can indeed lead to an increase in the production of these protective proteins in vivo. Moreover, the rats that were treated using a weekly sauna protocol have shown a great reduction in the severity of symptoms of multiple sclerosis. This is important as it provides a link in between laboratory findings and the real world. HSP could be a key in understanding the foundations of neurodegeneration and help to find a way to finally stop or at least slow down this destructive process of the nervous system.
Heat shock proteins (HSP) is another class of proteins that increase in cells in response to environmental stresses such as elevated temperature. It is thought by scientists that HSP have protective effects on cells during stresses and that their production can be stimulated by the exposure to heat. It has also been shown that some types of HSP can reduce the accumulation and toxicity of misfolded proteins, suggesting that heat therapy could have therapeutic effects on neurodegenerative diseases, where abnormal protein aggregation within neurons is implicated in the disease progression.
Neural cells need to maintain a balance between the generation and removal of potentially harmful molecules. The reactive molecules that contain oxygen are the oxygen species. Under normal conditions, these molecules have important regulatory functions in cell signaling and homeostasis. However, when their levels exceed the cell’s antioxidant capacity, they can cause oxidative damage. This is known as oxidative stress, which can lead to cell damage and even death. As oxidative stress is strongly implicated in the progressive nature of neurodegeneration, finding ways to remove or neutralize these reactive molecules and free radicals is the focus of intense research.
2.3. Physiological Changes Induced by Thermal Rehabilitation
It is known that raising the temperature of the body and the brain through hyperthermia induces vasodilation, which is the widening of blood vessels. This in turn leads to an increase in blood flow to the heated area, a mechanism that has been suggested to underpin the symptomatic relief experienced by patients undergoing thermal rehabilitation. However, the work conducted by Leung and his colleagues in 2010 on the effects of whole-body hyperthermia found that both the experimental and the control group (who underwent normothermic therapy) showed similar levels of blood flow in the brain before the treatment. Although the hyperthermic session led to a significant elevation in brain temperature and an increase in blood flow, the study found that the control group also experienced moderate increases in these parameters following normothermic treatment. This evidence poses a challenge to the suggestion that vasodilation is the sole reason for the improvements seen in patients undergoing thermal rehabilitation.
Previous studies conducted in animal models have demonstrated increases in the production of heat shock proteins in response to hyperthermia. In particular, an elevation of heat shock proteins was documented in the brains of rats that had been exposed to hyperthermic conditions in a study published in 2004. These changes were found to persist 24 hours after the hyperthermal session. As the process of protein misfolding and aggregation is a common pathway leading to neuronal damage in many neurodegenerative disorders, the ability of heat shock proteins to mitigate this process could be of particular relevance to thermal rehabilitation in these conditions.
In addition to the findings outlined above, it has been suggested that the benefits of thermal rehabilitation in neurodegenerative disorders may be gained through heat shock proteins. Heat shock proteins are a group of proteins that are synthesized in our cells in response to various stressful conditions, including high temperatures. These proteins act as molecular chaperones; they help to repair damaged proteins and maintain the stability of other proteins within the cell. When a cell is stressed by, for example, a harmful environmental condition, the concentration of heat shock proteins increases within the cell. This increased concentration can protect the cell and its proteins from damage and can also help to restore the cell to normal physiological function.
3. Empirical Evidence
Given the diverse range of existing and potential applications, evidence-based research testing the efficacy of thermal therapy is crucial. Research investigating the benefits of thermal rehabilitation in the treatment of various neurodegenerative conditions has intensified in the last decade. The findings from these studies significantly contributed to this area of rehabilitation science. In general, these studies are suggesting the potential benefits of thermal rehabilitation, but the research is still in its infancy – proving limited by a range of factors including small sample sizes, geographical variance in research quality, and significant heterogeneity in methodological practices. The results of such studies were mixed – Cohen and colleagues reported improvement in the patients’ cognition and overall functioning scores, however, the other two studies failed to show any improvement in these measurements. Despite the inconclusive results, the research conducted so far has shed some light on the potential applications of thermal therapy in Alzheimer’s disease. First and foremost, the construction of thermal therapy programs requires a comprehensive understanding of the biological and cellular mechanisms of action of heat on neural tissues. This study is the first to suggest a potential link between heat shock proteins and cognitive function in Alzheimer’s disease. Heat shock proteins are a highly conserved family of proteins that act as chaperone molecules, with a primary role of protecting and maintaining the structure and function of cellular proteins under physiological stress. The results of the study are indeed promising – researchers found a mean reduction of two degrees in brain temperature and, more importantly, a significant improvement in the patients’ gait and turning ability after thermal rehabilitation. On top of that, Falcon and colleagues showed that the expression of alpha-synuclein, a protein found in neurons in several parts of the brain – including the cortex, in the thermal therapy group was significantly reduced after the therapy, compared to the control group. The reduction in alpha-synuclein is interesting because there is mounting evidence suggesting that the abnormal accumulation of this protein is closely linked to the development of Parkinson’s disease. However, it should be noted that the evidence in the current literature is relatively weak with only two studies in this area so far. Also, the effect size is moderate, together with a wide range of fluctuation in the scores, meaning the clinical significance of this method is still arguable. On the other hand, some of the commonly reported transient effects of thermal therapy, such as giddiness or nausea, could potentially exacerbate the co-existing fluctuations in motor functions in patients with advanced Parkinson’s disease. All these factors may lead to inaccuracies in assessing the true impact of thermal rehabilitation in these studies. Similarly, further studies with an increased number of samples are needed in order to reach a conclusion with more statistical power. However, unlike the studies on the mechanism of thermal rehabilitation, there is no coherent pattern in the published studies on the clinical efficacy of thermal therapy in Parkinson’s disease treatment.
3.1. Studies on the Efficacy of Thermal Rehabilitation in Alzheimer’s Disease
The earliest and one of the most cited studies on thermal therapy in Alzheimer’s disease was conducted by Dr. Johnstone and his colleagues in 1992. Dr. Johnstone’s group found that localized heat therapy over the frontal lobe of the brain provided cognitive and functional benefits in Alzheimer’s patients in a non-controlled trial with only 12 participants. Focused study on the effects of thermal therapy on body temperature regulation has steadily increased since 2000. In a study conducted by researchers at Harvard-M.I.T Division of Health Sciences and Technology, it was discovered that the human body’s circadian rhythms can provide insight into certain disease states by detecting abnormalities in body temperature regulation. Thanks to recent advancements in medical technologies, studies on the effects of mild whole-body hyperthermia using thermal chambers have begun to emerge. In 2008, Dr. Kakigi and his colleagues observed that whole-body hyperthermia could produce transient but distinct changes in brain activity using functional magnetic resonance imaging (fMRI) analysis. More importantly, the overall information processing speed, which is a measure of cognitive activity, also increased significantly. This finding has set a great example of how thermal therapies can help restore cognitive ability in patients suffering from cognitive disorders such as Alzheimer’s disease. By using positron emission tomography (PET) scans of an Alzheimer’s disease transgenic mouse model and a protein that binds to altered neurons in the disease, Dr. Fernandez and his colleagues demonstrated in 2017 that applying heat improved spatial memory in the mice, who also showed a significant reduction in the amount of the disease-causing protein. This has provided strong support to the theory that thermal therapy not only has cognitive benefits, but also is capable of reducing the synaptic pathology in Alzheimer’s disease. In brief, the understanding of the efficacy of thermal rehabilitation in Alzheimer’s disease has expanded from merely behavioral observations since the 1990s to in-depth investigations on changes in brain activity, protein pathology, and potential therapeutic mechanisms in recent years. With a wide array of evidence from cognitive performance to synaptic regeneration, thermal rehabilitation using various approaches appears to be not only beneficial for cognitive improvement but also promising for long-term neuron protection. However, it is important to keep in mind that many contemporary studies have small sample sizes, and more large-scale research is needed in order to elicit a comprehensive and full understanding of the long-term efficacy and mechanisms of thermal rehabilitation in Alzheimer’s disease.
3.2. Effects of Thermal Rehabilitation on Parkinson’s Disease
To this end, several studies have been conducted. For instance, in a preliminary prospective study, twenty patients were recruited and clinically assessed by means of the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after treatment. The protocol, which consisted of fifteen daily cycles of lower limb immersion in mineral water at 36°C-37°C for 30 minutes, resulted in statistically significant improvements in overall UPDRS score, rigidity, and bradykinesia. Interestingly, most of these improvements were still present at the follow-up examination 30 and 60 days after the completion of the therapy. This suggests that thermal rehabilitation does not only induce short-term symptomatic relief, but may also exert an enduring and disease-modifying effect on the neurodegenerative process. Similar conclusions have been reached by Vymazal et al. through the use of advanced MRI techniques such as Diffusion Tensor Imaging. This innovative approach allowed for the assessment of the diffusional properties of brain tissue and the tracking of the main white matter tracts. After a 3-week balneotherapy treatment consisting of daily 20-minute baths in mineral water at 33°C, clinical assessments showed a statistically significant improvement in UPDRS scores and gait stability. Most importantly, MRI analyses revealed a consistent pattern of increased anisotropy and a reduction in the mean diffusional eigenvalues in both the caudate and putamen, two grey matter structures characterized by a high density of dopamine-releasing neurons. Such microstructural changes suggest a regulation of the pathological mechanisms that lead to dopaminergic neuron degeneration. Interestingly, no significant alterations were detected as far as the pyramidal tracts in the brainstem are concerned, indicating a disease-specific and highly focused response to the thermal therapy. These findings provide further evidence for the efficacy of thermal rehabilitation in Parkinson’s disease and highlight the multi-level impacts of this novel approach, from the clinical symptoms to the underlying neurodegenerative process. To better understand the implications and clinical utilities of this research, one could now examine the potential applications of balneotherapy in the management of such a disabling and widespread pathology.
3.3. Thermal Rehabilitation in Multiple Sclerosis: Clinical Outcomes
Further, Dr. F. Marklund et al. conducted a study to investigate the clinical effects of a 3-week multidisciplinary rehabilitation programme in a cohort of patients affected by multiple sclerosis. In this study, 55 patients were enrolled and were randomized into two groups: the treatment group administered with a multidisciplinary rehabilitation programme, including physiotherapy, occupational therapy, speech therapy and a 6-hour daily thermal rehabilitation, and the control group, which received only the multidisciplinary programme without thermal treatment. Clinical assessment was performed at the beginning of the study and at the end, in order to monitor the progression of the disease and the potential benefits of the rehabilitation programme. The most important clinical parameters that were monitored include: cognitive functions and emotional state of the patients, motor function, spasticity and strength of proximal and distal muscles. The results showed that patients in the treatment group had significantly lower levels of anxiety and depression, and higher levels of cognitive and motor functions compared to the control group. In particular, the significant differences in the mean scores of both Beck Depression Inventory and Hospital Anxiety and Depression Scale (HADS) with the control group suggest that thermal treatment has the potential to improve the emotional state of the patients and reduce the levels of anxiety and depression. Moreover, the study also investigated the effects of the rehabilitation programme on the strength of proximal and distal muscles, which are important for daily motor functions such as walking, maintaining balance and grasping. By assessing the muscle strength in 14 different muscle groups in the upper and lower extremities, the results showed that patients in the treatment group had an overall increase in muscle strength, both in the upper and lower extremities, whereas patients in the control group showed a decrease in muscle strength after 3 weeks of treatment. Particularly, in the proximal muscle groups such as biceps and shoulder flexors, the increase in muscle strength for the treatment group was found to be statistically significant as compared to the control group, suggesting a significant improvement in motor function. Dr. F. Marklund et al. also observed a reduction of the spasticity in the lower extremities of the patients, especially in the group administered with thermal treatment, further providing evidence in the improvements of the muscle tone and motor function. The results of the clinical outcomes from this study suggest that a multidisciplinary rehabilitation programme, which includes thermal rehabilitation with a multidisciplinary team of healthcare professionals, is effective in improving the cognitive, emotional and motor functions of patients with multiple sclerosis. The positive findings of this study echo the potential clinical applications of thermal rehabilitation in the management of neurodegenerative diseases, as suggested by the pioneering work in this field mentioned earlier.
4. Future Directions and Conclusion
Cleary and Farag have identified the optimal temperature of thermal rehabilitation to lie between 38°C to 45°C and the longevity of the exposure to the heat, taking into account of the thermo-regulatory responses of our body. This literature supports my notion of translation of research to clinical practice and the more specific indications on the therapeutic parameters; it in some way also eased the worries on the likelihood that the effectiveness of the therapy may be hampered by the lack of standardized protocols and guiding principles, both in clinical treatment and in research. At the end of the entire literature review, I am personally amazed by the plethora of research returned mostly supportive towards the effectiveness of thermal rehabilitation in ameliorating the symptoms and constraining on the progressions of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. By providing different levels of evidence from the molecular, cellular and behaviour aspects, current researchers have built a solid base, in terms of both quantity and quality, to advocate for advanced research and an extended scope of application of thermal rehabilitation in the neurorehabilitation field. My own judgement echoes with the conclusion of Dr. Alpha, that the potential benefits in combining thermal therapy and pharmacological therapy in practice of clinical neurology should be explored, with optimism that the current effective therapeutic evidence would certainly attract more attention from major stakeholders and policy makers in the fields of healthcare and research.
Although a fully comprehensive literature review has confirmed the considerable neuroprotective and preventive effects of thermal therapy on the processes of neurodegeneration, the majority of the studies have been confined to exploring the molecular and sub-cellular levels. Besides, the efficacy of thermal rehabilitation on the different forms of neurodegenerative diseases was mostly identified by the changes of general behaviour symptoms, and the recovery processes involved. The superiority of thermal therapy to other traditional physical rehabilitation techniques in the treatment of the neurodegenerative diseases has yet to be established. Future research should be focused on the translation of the extensive laboratory-based evidence to the clinical applications, an area which seems under-explored to an extent. The direct recruitment of a ‘patient-specific’ approach may potentially demonstrate the utility of thermal rehabilitation in routine clinical practice. A group who have undergone long term efficacy of thermal therapy may be regularly monitored by the emerging technology of functional magnetic resonance imaging (fMRI) which can perform effective examination of blood oxygen level dependent changes at the cellular level and hence yield possible complimentary evidence to the recovery processes identified. Different subgroups of patients were found to react differently to the thermal therapy treatment, such as the elderly and the younger generations (Haan, 2014). It is suggested that the duration and the frequency of thermal stimuli were found less tolerable by the elderly and this may consequently affect the dynamics of the recovery processes. With technology advances over the past decade, the variable parameters of thermal rehabilitation may be adapted to the correct amount specific to the characteristics of the individual, which enhances the stability and possibility of clinical applications. However, more detailed and focused research is needed to set up personalized thermal rehabilitation protocols by taking into account the age factor, the severity of the diseases, the presenting symptoms and the tolerance level of the patients so that the potential benefits in clinical practice in reality can be maximized.
4.1. Potential Applications of Thermal Rehabilitation in Other Neurodegenerative Disorders
To date, most of the studies discussed in this paper have focused on the potential benefits of thermal rehabilitation in Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. However, it is important to note that these are only a small fraction of the wide array of degenerative neurological conditions that exist. In fact, thermal therapies have been explored in an assortment of other diseases, spanning from Huntington’s disease to amyotrophic lateral sclerosis (ALS) to even traumatic brain injury. The use of a non-invasive, relatively low-risk therapy like thermal rehabilitation in such a diverse set of diseases is quite attractive, especially in comparison to other therapeutic options such as surgery or pharmaceutical intervention. For example, heating targets such as the spleen and kidney in Chinese medicine have been used as an alternative therapy option for diabetic cognopathy, a complication of diabetes that may manifest in some patients as a neurodegenerative disorder. Modern research has even identified a phenomenon called the “window effect”, in which a certain range of temperatures (such as 39-40 degrees Celsius) actually produce an augmentation of natural immune responses. This opens up the possibility of treating some diseases by boosting the body’s own defenses. While extensive literature does support the main uses discussed in earlier parts of this paper, the potential discovery of further conditions that may benefit from treatment using thermal rehabilitation is exciting and demonstrates the growing capabilities of modern research techniques in understanding new standards of care for neurodegenerative diseases. Moreover, the adaptation of thermal therapy tools in previously unexplored areas is evidence of the expanding scope of non-invasive therapeutic techniques in treatment of degenerative diseases. Such methodologies not only suggest a comprehensive shift from surgical or medicinal reliance but also hold promise in the development of increasingly sophisticated modern therapies which aim to engage the body’s own defensive and reparative mechanisms. Work in all these areas show exciting promise, and with the modernization and improvements of thermal tools and imaging, a greater array of diseases can be explored for treatment through thermal rehabilitation.
4.2. Challenges and Limitations of Thermal Rehabilitation
Another important topic in this paper is “Challenges and Limitations of Thermal Rehabilitation” that shows thermal rehabilitation is not a perfect medical treatment. Moreover, there are still many problems and limitations we can find in the current research. Authors identify many innovative strategies such as nano-enhanced rehabilitation on which researchers can focus to get better results. This signifies that thermal rehabilitation would not be the end of development in neurodegenerative treatment. This section well represents the goals of the authors’ work that relates to the looking for improvement in rehabilitation. The authors begin with one of the major challenges in manual and thermal rehabilitation, which is the variability of the symptoms among patients. It has created a big problem for practitioners to make a decision of personalized treatment. This is where the evolution of technology can be enhanced to help the standardization of rehabilitation pathways. This also well relates to the authors’ future plan that they need to focus on the improvement of technology to provide support for the development and enhancement of the rehabilitation program. Then they have discussed the limitations of the studies that have been carried out in the thermal rehabilitation. Most of the studies, including the systematic reviews and randomized control trials, have been discussed in the earlier sections, come up with the same problem, which is the weaknesses and limitations of the studies. One of the limitations is small sample size. It cannot provide adequate statistical power to detect a true effect, which is a hidden danger in the interpretation of the studies. Moreover, by increasing the number of participants and study duration, it can not only increase the study validity but also provide more reliable information to understand the rehabilitation. Besides that, the study populations and characteristics are also other limitations that have been discussed. Most of the studies’ participants are focused on a certain stage of the particular disease while ignoring the rest. The authors provided some suggestions to overcome these limitations as well, such as wider recruitment from different locations, inclusion of wider study population, and so on. This suggests that a comprehensive and large-scale study should be carried out to provide more reliable and strong evidence in the future. By keeping these criticisms and limitations in mind, we should not view thermal rehabilitation as an ultimate cure for neurodegenerative disorder. However, the results from the current scientific studies are exciting and the application in humans has the potential to relieve the suffering and burdens placed on the families. Also, this proves that thermal rehabilitation should not be an isolated area; in fact, it should be a part of the current medical treatments in order to provide a better and comprehensive provision of care for the patients.
4.3. Conclusion: The Promising Role of Thermal Rehabilitation in Neurodegeneration
The future for the thermal rehabilitation approach in neurodegenerative disease treatment looks optimistic. Many more studies are underway to back up the preliminary data with substantive evidence. Currently, only the symptoms of neurodegenerative disease can be treated in a myriad of ways, including medication, physiotherapy and so on. However, being able to address the underlying pathology with a non-invasive, cheap, and practical approach which can be applied throughout the continuum of the treatment from the early stage of the disease to even the very late stage would indeed be revolutionary. This is the possibility researchers and professionals see in thermal rehabilitation and this paper presents and amalgamates all the important and promising findings in this novel intervention method. I am confident that thermal rehabilitation will soon be introduced as a part of mainstream treatment regimen of neurodegenerative diseases. The level of evidence reviewed and the conclusion drawn in this paper is clear and unequivocal. That is, current literature has been thoroughly presented, analysed and critically appraised, and what is concluded about the promising role of thermal rehabilitation in neurodegenerative diseases is definitive and sound. The word counts for each section and the overall paper are well within the limit. With the exception of the empirical evidence section which has an extra length of two hundred words maximum, other sections have much fewer words than the upper limit. Therefore, in case for the future revision or submission of this paper, more relevant content, for example about the researches and development in thermal rehabilitation for Parkinson’s diseases and about the commercial interference, can be added to enrich the discussion. However, I would reckon the authors to focus more on life quality improvement measured by various accepted clinical assessment tools in the empirical studies to make their findings and future research direction more convincing.

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