Information on the studies that included poststroke individuals, in their samples.
\r\n\tThe aim of this book will be to describe the most common forms of dermatitis putting emphasis on the pathophysiology, clinical appearance and diagnostic of each disease. We also will aim to describe the therapeutic management and new therapeutic approaches of each condition that are currently being studied and are supposed to be used in the near future.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"278931ae110500350d8b64805c70f193",bookSignature:"Dr. Eleni Papakonstantinou",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7934.jpg",keywords:"Atopic eczema, Interleukin, Topical corticosteroids, Hand eczema, Blisters, Pruritus, Irritant contact dermatitis, Allergic contact dermatitis, Discoid eczema, Sebaceous glands, Inflammatory dermatitis, Facial rash",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 5th 2019",dateEndSecondStepPublish:"March 19th 2019",dateEndThirdStepPublish:"May 18th 2019",dateEndFourthStepPublish:"August 6th 2019",dateEndFifthStepPublish:"October 5th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"203520",title:"Dr.",name:"Eleni",middleName:null,surname:"Papakonstantinou",slug:"eleni-papakonstantinou",fullName:"Eleni Papakonstantinou",profilePictureURL:"https://mts.intechopen.com/storage/users/203520/images/system/203520.jpg",biography:"Dr. med. Eleni Papakonstantinou is a Doctor of Medicine graduate and board certified Dermatologist-Venereologist. She studied medicine at the Aristotle University of Thessaloniki, in Greece and she continued with her dermatology specialty in Germany (2012-2017) at the University of Magdeburg and Hannover Medical School, where she completed her dissertation in 2016 with research work on atopic dermatitis in children. During this time she gained wide experience in the whole dermatological field with special focus on the diagnosis and treatment of chronic inflammatory skin diseases and also the prevention and treatment of melanocytic and non-melanocytic skin tumors. Her research interests were beside atopic dermatitis and pruritus also the pathophysiology of blistering dermatoses. In addition to lectures at german and international congresses, she has published several articles in german and international journals and her work has been awarded with various prizes (poster prize of the German Dermatological Society for the project: 'Bullous pemphigoid and comorbidities' (DDG Leipzig 2016), 'Michael Hornstein Memorial Scholarship' (EADV Athens 2016), travel grant (EAACI Vienna 2016). Since 2017, she works as a specialist dermatologist in private practice in Dortmund, in Germany. Parallel she co-administrates an international dermatologic network, Wikiderm International and she writes a dermatology public guide for patients, as she is convinced that evidence-based knowledge has to be shared not only with colleagues but also with patients.",institutionString:"Private Practice, Dermatology and Venereology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"66130",title:"Neuromuscular Electrical Stimulation and Electromyographic Biofeedback as Adjunctive Modalities in the Treatment of Oropharyngeal Dysphagia in Stroke",doi:"10.5772/intechopen.84942",slug:"neuromuscular-electrical-stimulation-and-electromyographic-biofeedback-as-adjunctive-modalities-in-t",body:'\nDysphagia is a symptom related to swallowing disorders that impede or hamper safe, efficient, and comfortable oral ingestion [1], characterized by the abnormality in the transference of bolus from the mouth to the stomach [2]. In addition to compromising the swallowing process, dysphagia may impair overall health, the nutritional status, and lung conditions, impacting quality of life as well [3, 4].
\nThere are many neurological diseases that can affect the neural structures which control the complicated mechanisms of oropharyngeal swallowing. Most symptoms and complications from neurogenic dysphagia are due to sensory-motor change of the oral and pharyngeal phases of swallowing [5]. In adults and in the elderly population, dysphagia often derives from stroke [6].
\nDifferent proposals for the rehabilitation of oropharyngeal dysphagia have been researched over the years. Thus, literature review studies demonstrate the effectiveness of using protective and facilitating swallowing maneuvers, showing physiological changes in specific aspects of swallowing in normal subjects increasing or decreasing the pharyngeal contraction, the lingual pressure, the upper esophageal sphincter relaxation and contraction, according to the different techniques [7] and in the rehabilitation of oropharyngeal dysphagia reducing or eliminating aspiration and improving functional outcomes in specific populations [8, 9].
\nOrofacial myofunctional exercises are a therapeutic approach for the treatment of oropharyngeal dysphagia [10]. In poststroke individuals, tongue isometric exercises result in an increase in tongue force, with an associated improvement in swallowing pressure, airway protection, and tongue volume in acute or chronic phases [11].
\nIn a late poststroke case, these tongue exercises were associated with improved bolus control and increased oral intake [12]. The use of surface electromyography (SEM) as a therapeutic biofeedback is a resource described in various areas of health, with studies showing clinical efficacy for a variety of neuromuscular disorders. The electromyographic biofeedback can be used to aid in muscle relaxation, coordination, and/or muscle response pattern training, as well as increased recruitment of motor units during muscular activity.
\nThe McNeill Dysphagia Therapy Program (MDTP), which improves the timing of physiological events during swallowing, is another rehabilitation modality for patients presented with neurogenic dysphagia. Following MDTP, subjects presented with chronic dysphagia showed temporal coordination of swallowing components close to that of healthy individuals, thus suggesting a normalization of swallowing timing [13].
\nAs a therapeutic strategy aimed at the rehabilitation of oropharyngeal dysphagias, the electromyographic biofeedback [14] provides improved strength in swallowing and its coordination, understood as the best muscle recruitment during the function, associated with the attention and performance of cortical functions, simultaneously [15, 16]. Its use has been described in cases of dysphagia due to stroke [17, 18, 19, 20], as well as in cases of patients with sequelae from the treatment of head and neck cancer [19], with improvement in swallowing and consequent increase in the oral intake of patients treated with biofeedback associated with conventional therapy.
\nNeuromuscular electrical stimulation (NMES) is another therapeutic approach used in the rehabilitation of oropharyngeal dysphagia (NMES). NMES has been recommended as an adjunctive modality to improve the results of exercises based on dysphagia therapy. According to Wijting and Freed [21], NMES is the application of electrical current pulses to the skin to stimulate muscle contraction by peripheral motor nerves. The electric current causes a depolarization of the peripheral motor nerve, usually where the nerve enters the motor end plate, which, in turn, will elicit muscle contraction.
\nNMES has drawn the attention of speech therapists since the initial application for dysphagia by Freed et al. [22]. Some studies have shown improvement in swallowing physiology [22, 23, 24] and quality of life [25] after using NMES in individuals presenting with oropharyngeal dysphagia and also, specifically, in poststroke patients [26, 27, 28]. The increase in laryngeal excursion has been described as a physiological change in swallowing following NMES, related to the lowering of the hyoid bone during rest, in patients with neurogenic dysphagia [29, 30], and to the increase in the elevation of the larynx during swallowing [31].
\nIn studies reporting higher level of oral intake [31, 32], decreased severity of dysphagia in patients with moderate dysphagia [33], increased sensitivity in poststroke individuals [34], and decreased laryngotracheal aspiration [31] were found as well. On the other hand, some studies found no difference in the clinical outcomes of patients undergoing rehabilitation with NMES, as compared to conventional therapy [35, 36].
\nIn view of the possibility of using technological resources in the diagnosis and treatment of oropharyngeal dysphagia, this chapter presents the theoretical and procedural frameworks aimed at the application of EMG biofeedback and NMES as supporting methods in the treatment of oropharyngeal dysphagia, in cases affected by stroke.
\nRegarding the effect of NMEE on swallowing, there is not a uniform stimulation protocol in terms of duration, number of sessions, and parameters of the electric current. Some studies show positive results of NMES in the treatment of dysphagia, but others suggest negative effects on hyolaryngeal elevation or do not find differences with respect to conventional therapy. It is known that NMEE can directly modulate swallowing and interfere with the mechanisms of central control and execution. In addition, the closure of the vocal folds during swallowing and speech is modified by NMES, owing to weakness and paresis [37].
\nAdditionally, the physiological responses obtained by NMEE can also be influenced by age and level of stimulation. A study [38] found interactions between age and stimulation amplitude on lingual and pharyngeal functions during swallowing. The anterior tongue pressure was reduced by motor stimulation in both age groups; however, the posterior lingual-palatal pressures were selectively reduced in adults. The base of tongue (BOT) pressures were increased by sensory stimulation in the elderly but decreased in young adults. Hypopharyngeal pressures were increased in both groups by motor stimulation. Therefore, age and NMEE level should be taken into account when planning the rehabilitation of swallowing disorders.
\nSpecifically on the effectiveness of the application of NMES in poststroke dysphagia patients, several methods are proposed for NMES application, including level of stimulation, electrode placement, tasks requested during NMES, and frequency and duration of sessions. Aiming at understanding how the research has been conducted, Table 1 presents the information on the studies that included poststroke individuals, in their samples.
\nResearch/authors | \nBeom et al. [39] | \nKushner et al. [40] | \nSun et al. [41] | \nTerré et al. [42] | \nLee et al. [43] | \nToyama et al. [44] | \n
---|---|---|---|---|---|---|
Stroke data | \n2.4 ± 2.1 months after stroke Cortex and subcortex | \n15.7 days after stroke Brain stem, brain hemisphere, and intracerebral hemorrhage | \nBrain stem and brain hemisphere | \n5 and 7 months after stroke | \n5.5 ± 2.1 day after stroke Cortical and subcortical Brain hemisphere | \n25.2 ± 25.9 weeks after stroke Hemorrhagic and ischemic | \n
Age | \n66.1 ± 19.5 years | \n19–89 years | \n70.1 ± 8.9 years | \n32–71 years | \n63.4 ± 11.4 years | \n63.6 ± 21.4 years | \n
Gender | \n3 males and 4 females | \n38 males and 27 females | \n24 males and 5 females | \n7 males and 2 females | \n22 males and 9 females | \n12 males | \n
Stimulation level (device) | \nTolerance (STIMPLUS DP200) | \nTolerance (VitalStim) | \nTolerance (VitalStim) | \nTolerance (VitalStim) | \n120% of the mean of 3 tolerance threshold measures (VitalStim) | \nMotor (HPC device) | \n
Electrode placement | \nNear the motor point of the digastric anterior belly muscle | \nDifferent for each patient | \nA pair, horizontally, above the hyoid bone and another, on the thyroid cartilage | \nA pair, horizontally, on the mylohyoid muscle and another on the thyrohyoid one | \nInfrahyoid region | \nRegion of geniohyoid, mylohyoid, and digastric anterior belly muscles and thyrohyoid musculature | \n
Tasks required | \nNone | \nExercises to increase strength, resistance, and amplitude of movement and mobility of the orofacial, lingual, and laryngeal musculature | \nRepeated effort swallowing | \nNone | \nTactile-thermal stimulation, tongue and closing-elevation larynx exercises, effort swallowing, and Mendelsohn, Masako, and Shaker maneuvers | \n3–10-minute NMES series, with 2-minute rest intervals, followed by conventional therapy with tongue exercises, tactile-thermal stimulation associated with dry effort swallowing, and Mendelsohn maneuver | \n
Duration of sessions | \n30 minutes | \n60 minutes | \n60 minutes | \n45 minutes | \n30 minutes with NMES associated with conventional therapy | \n40 minutes | \n
Number of sessions per week | \n5 sessions | \n5−6 sessions | \n5 sessions | \n5 sessions | \n5 sessions | \n5 sessions | \n
Total of sessions | \n20 sessions | \n18 ± 3 sessions | \n12 sessions | \n20 sessions | \n15 sessions | \n40 sessions | \n
Exams carried out | \nAssessment by ASHA NOMS protocol and videofluoroscopy | \nFOIS | \nClinical assessment, FOIS, and perceptive evaluation of swallowing ability by the visual analog scale | \nFOIS, patient’s satisfaction scale, and videofluoroscopy, after and 3 months following therapy | \nFOIS and videofluoroscopy | \nFOIS, videofluoroscopy, and assessment of the anterior and upper displacements of the hyoid bone and larynx | \n
Results | \nImprovement in the dysphagia and ASHA NOMS scales and in the videofluoroscopy | \nImprovement in the FOIS scale and better FOIS score, as compared to controls | \nImprovement in the FOIS scale and maintenance from 6 months to 2 years Improvement of the dysphagia degree and of the perceptive swallowing ability, following 6 months and stable after 2 years | \nImprovement in the FOIS and in the patient satisfaction scales Decrease of aspiration and of the delay in the triggering of the swallowing reflex | \nImprovement in the FOIS and swallowing function, in all periods | \nImprovement in the FOIS and dysphagia scales Greater anterior and upper displacement of the hyoid bone Greater upper laryngeal displacement in the experimental group | \n
Information on the studies that included poststroke individuals, in their samples.
Studies with patients suffering from stroke who used the sensory level of stimulation showed improvement in swallowing function and that the increase in the sensorial input to the cortex can reduce swallowing problems. The thyrohyoid muscle stimulation was used in most studies, using motor stimulation to increase the elevation of the larynx.
\nStimulation of the thyrohyoid muscle was used in most studies, using motor stimulation to increase the elevation of the larynx. Most studies show positive effects of NMES in the performance of swallowing in patients presented with poststroke dysphagia, especially when the stimulus is applied at the sensory level or when the level of motor stimulation is applied to the infrahyoid muscles, during swallowing [45].
\nThus, speech therapy sessions should be performed according to the selected therapy protocol, taking into account the characteristics of the patient’s swallowing disorder and the goals to be achieved by the intervention.
\nNeuromuscular electrical stimulation is performed with a dual-channel electrotherapy system with an 80 Hz fixed current pulse and a 700 μs pulse duration (VitalStim, model 5900, Chattanooga Group), applied by a qualified professional.
\nPrior to placing the electrode in the skin, the anterior part of the neck should be cleaned with alcohol, so as to remove body oils that can interfere with the electrode contact. The placement of the electrodes used during therapy, for all participants, should meet their physiological needs of the patient. After placing the stimulation electrodes, the amplitude of the stimulation is increased by small increments.
\nThe amplitude of the sensory and motor levels of NMES is determined based on the patient’s description of the feeling, while the amplitude is increased from zero to the maximum tolerance. The minimum level of sensory stimulation is determined when the patient reports a tingling sensation, while the minimum motor level corresponds to sensation of tightness or pull [46].
\nThe stimulation amplitude is set before therapeutic activities, individually determined at the motor or sensory levels, with functional tasks involving the swallowing of saliva or food of different volumes and consistencies, according to the possibility of safe feeding, identified by means of instrumental examination.
\nSurface electromyography (SEMG) allows access to the physiological parameters of swallowing. Quantitative and qualitative analyses show that the normal swallowing in adults varies from individual to individual [47, 48] and is influenced by age. The pharyngeal phase is longer in children under 12 than in adults but with similar amplitude of muscle electrical signal [49], consistency, and bolus volume [50, 51, 52].
\nDuring electromyographic evaluation of swallowing, the activity of the suprahyoid muscles is 30–50% higher than that of the masseter muscles, and with advancing age, there is a decreased activity of the suprahyoid muscles and an increased masseter activity, with no statistically significant difference between men and women [47]. The literature has also shown a significant increase in the duration of muscle activity during swallowing, in patients over 70 years [53], and no difference between genders, both in the amplitude and duration of muscle activity, in the different age groups assessed [47, 53].
\nIn addition to age, the use of dental prostheses influences the electromyographic activity. Authors [54] observed that, from the oral rehabilitation with implant-supported prostheses, the amplitude of the electromyographic signal for swallowing was the same found for dentate subjects, but the duration of muscle activity in this function is higher in users of prostheses. Authors [55] found a significant drop in activity for the masseter muscle following implant-supported oral rehabilitation in the elderly, resulting from the process of adaptation to the new conditions of stability generated by the fixation of total prostheses to the lower arch, in these subjects.
\nAs an adjunctive method in the rehabilitation of oropharyngeal dysphagia, the electromyographic biofeedback can be used for the training of muscle relaxation, coordination, and/or muscle response patterns, as well as in the recruitment of a greater number of motor units during the activity of the stimulated muscle, in order to allow the patient to learn and monitor new muscle patterns using visual and/or auditory reinforcement [56, 57].
\nThe application of electromyographic biofeedback in the treatment of dysphagia aims, primarily, at improving the swallowing strength and its coordination [16]. Studies show improvement in swallowing and, consequently, an increase in the oral intake of patients treated with biofeedback combined with conventional therapy [20, 24]. Research with this technique applied to swallowing disorders was initially carried out in a clinical case involving dysphagia of unknown etiology, which presented spasticity, rehabilitated with 20 sessions of EMG biofeedback and relaxation exercises to be done at home, with a significant improvement in the difficulty in swallowing, and maintenance of the results following 6 months of the end of the intervention [58].
\nThe literature has shown improvement of swallowing in patients presented with poststroke neurogenic dysphagia, with an increased oral intake after the application of the biofeedback technique associated with conventional therapy, following seven training sessions [24] and after a 10-hour training carried out in a week [20], even in individuals previously rehabilitated with conventional exercises without success [20, 24]. A study [20] further reinforces that the functional improvement of swallowing was kept in six out of ten patients, up to 1 year after the intervention.
\nAnother study examined the effectiveness of this technique in acute poststroke subjects using Mendelsohn’s maneuver and EMG biofeedback for 2 weeks of rehabilitation and 2 weeks of non-rehabilitation, with groups which intercalated weeks of rehabilitation and non-rehabilitation and were assessed in each phase. In the rehabilitation week, the subjects were trained daily, twice a day, the first session being the learning of the maneuver and the remaining ones, training, during 30–40 swallowings. Significant changes were observed in hyolaryngeal duration and excursion (anterior and vertical), following the rehabilitation weeks [59].
\nCrary et al. [19] assessed the effectiveness of rehabilitation with EMG biofeedback in 25 patients presented with neurogenic dysphagia (poststroke) and in 20 subjects with mechanical dysphagia (posttreatment of head and neck cancer) in a 50-minute therapy, five times a week therapy, plus home training. All subjects improved their oral intake, with 92% improvement in neurogenic dysphagia and 80% in mechanics. Although the best result was seen in subjects presented with neurogenic dysphagia, they needed more sessions to complete the intervention, as compared to those with mechanical dysphagia.
\nConventional therapy associated with electromyographic biofeedback should be performed during direct swallowing therapy, aiming at the learning of the new swallowing pattern. The strategies of the treatment with electromyographic biofeedback aim to achieve the neuromuscular adjustments required for the approximation of normal physiological patterns of the electromyographic recording, mainly of the suprahyoid muscles.
\nAdditionally, the balance and coordination between different muscle groups, mainly those which elevate the jaw, orbicularis of the mouth, and suprahyoid muscles, can be approached, depending on the number of channels provided by the equipment. Figure 1 illustrates the EMG biofeedback therapy.
\nPatient and therapist during the direct training of swallowing, using the EMG biofeedback (4-channel neuroeducation equipment), monitoring the masseters, bilaterally, and suprahyoid muscles.
The normal electromyographic pattern of swallowing and that performed by the patients should be presented to them, during the training, establishing a target track for functional training, in which the patients perform the enabling swallowing strategies, whose effectiveness must have been previously proven in the instrumental examination, aiming at approximating their neuromuscular recruitment to the normality physiological pattern, which involves, mainly, increasing the amplitude of the electromyographic signal of the suprahyoid muscles during function (greater muscle recruitment in the function). In addition, the functional training may aim at improving the coordination among other muscle groups involved in swallowing, increasing the recruitment of tongue muscle activity, in order to propel the bolus safely from the oral cavity through the pharynx, and increasing the amplitude of the muscle activity exerted during the effort of swallowing [16].
\nFigure 2A and B illustrate the neuromuscular behavior accomplished before and after a month of training, using biofeedback, whose sessions were held three times a week, in a patient presented with oropharyngeal neurogenic dysphagia with no success in the rehabilitation with conventional therapy.
\n(A) EMG signal prior to therapy. (B) EMG signal after therapy.
The positive aspects of using the EMG biofeedback as an adjunctive method in cases of neurogenic dysphagia may pose this technique as a facilitator in terms of learning new neuromuscular patterns for swallowing, so as to provide the patient with a higher gain, as compared to the conventional therapy, as well as a probable longer effect of rehabilitation, since the EMG biofeedback involves the change of a previously learnt pattern, by means of the functional training therapy.
\nNMES has shown benefits in dysphagia therapy for individuals affected by stroke, mainly related to the classification of the degree of dysphagia and the level of oral intake. Some authors propose that the use of NMES associated with conventional therapy is more beneficial to the treatment of these individuals; however, there is a wide variety of electrode placement, level of the stimulus, and type and location of the stroke; thus, further studies are necessary to prove the efficacy of this treatment modality.
\nOn the other hand, swallowing training using EMG biofeedback can assist speech therapists in their clinical practice, enabling the patient to learn and monitor new muscle patterns, using visual and auditory reinforcement, and, from the learning and training of new neuromuscular recruitment, present a swallowing pattern as functional as possible, with a positive impact on quality of life.
\nHowever, further controlled and randomized clinical studies are necessary for a understanding on the contribution of the EMG technique, for there are still many doubts on the application method, the number of therapeutic sessions, and the characteristics of patients who can benefit from the training with EMG biofeedback.
\nThe authors declare no conflict of interest.
Research in plant-based medicine is gaining much more attention due to its lack of side effects, its large availability, and its multiple medicinal applications. In the past few years, this has also increased people’s awareness toward functional food, thus enhancing the consumption rate of legumes enormously [1]. The attention toward Mucuna improved colossally after 1937 when it was initially revealed that a huge quantity of levodopa is present in it. Genus Mucuna, which is familiar by different names (like: velvet beans, sea beans, cowitch, buffalo beans, cowhage, atmagupta, kapikachu, and dopa bean), is one of the conventional medicine performing crucial roles in both health and disease management. Mucuna is an excellent source of proteins, starch, micronutrients, dietary fiber, and bioactive compounds (L-DOPA), which play a great role in the traditional as well as modern medicine all over the world against Parkinson’s disease. The genus Mucuna belongs to the family Leguminosae distributed throughout the tropical and subtropical regions of various countries of the world comprising hundreds of species [2]. Recently, Pulikkalpura et al. [3] and Patil et al. [4, 5] studied the occurrence and biochemical activities of various Mucuna species in India.
Plant-based remedies are most beneficial remedies, having a cumulative effect of phytochemical and other bioactive components obtained from plants. Mucuna has various actions like antioxidant activity, anti-inflammatory activity, wound-healing activity, and activity against snake bite. Along with all this, Mucuna is also rich in nutritional and anti-nutritional compounds (rich in minerals) [6]. Mucuna is also well known for nematicidic effects and also possesses notable allelopathic activity, which was reported by Gliessman et al. [7]. In countries like Guatemala and Mexico, it is used as a coffee substitute. Along with that, in some countries (lower hills of the eastern country and Himalayas), it is commonly consumed as vegetable beans after frying and boiling. Mucuna seed powder has been used in active management of Parkinson’s disease in several countries due to its L-DOPA content.
In early health care system of India, Parkinson’s disease (PD) is known as “Kampavata”, which is a common neurological disorder related to neuromelanin containing nigrostriatal dopaminergic neuronal loss. Kampa means tremor and vata means lack of muscular movement. It was found via door-to-door survey in Bangalore (Karnataka, India) that 76 per 100, 000 (age adjusted) and 33 per 100,000 (crude prevalence) people suffered from Parkinsonism [8]. Out of that, 5–10% of individuals having PD belong to families with history of genetic disorders [9, 10]. The disease commonly occurs in the age group of 60–80. A survey on Parsi community in Mumbai shows that they were diminutively stable to PD [8]. Diagnosis of disease is sometimes difficult by clinical method, which involves analysis by considering large number of motor and non-motor symptoms in PD patients. PD is caused due to decrease in dopaminergic neurons in the substantia nigra pars compacta (SNpc) part of the brain, which leads to motor symptoms including rigidity, bradykinesia, tremor, and development of some non-motor symptoms in later stages of the disease. Although there is significant number of improvements in the medicinal and surgical actions against PD, scientists have not yet identified definite targets for disease management. According to research by Ramanan and Saykin, neurodegeneration is divided in to four main levels out of which aggregation and accumulation of abnormal or misfolded mutated proteins is crucial [11]. Some reports examine that oxidative stress (OS) and neuro-inflammation (NIF) are the main reasons of neurodegenerative disease. Thus, to tackle these neurodegenerative disorders, researchers have diverted their attention toward finding oxidative stress enzymes and pathogenesis of PD. Abraham et al. studied 115 cases of PD and concluded that catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (G-Px), and glucose-6-phosphate dehydrogenase (G6PD) levels are present in greater quantities in PD patients as compared to the control patients [11]. Various oxidative stress enzymes, pro-inflammatory cytokines, proteinase, reactive oxygen intermediates, and complement proteins are secreted by the immune cells against the neuronal cell damage response, which leads to inflammation. Along with mitochondrial dysfunction, altered proteolysis, oxidative damage of cells and Lewy bodies’ formation are some of the symptoms of Parkinson’s disease.
There are various strategies for the management for PD but there is no complete cure for this disease. The only management of the lowered dopamine levels is to control various metabolic inhibitions and enhancement pathways, preventing degeneration of neurons and other non-dopaminergic (surgelogical) treatment. L-DOPA (L-3,4 dihydroxy phenylalanine) is a non-protein amino acid used in the treatment of Parkinson’s disease. It acts as precursor of dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). It is synthesized by plants, animals, and microbes (bacterial and fungus) and has a different role in each source. Chemical synthesis of L-DOPA is easy but the purification of L and D forms is slightly complicated and expensive. Synthetic L-DOPA is considered as anti-nutritional factor and its consumption causes abdominal distention, vomiting, dyskinesia, nausea, etc. This happens when L-DOPA is converted to dopamine in the peripheral nervous system by enzyme dopa decarboxylase. Whereas, L-dopa is also used as the treatment against infertility recovering the spermatogenic harm to some extent. Numerous other secondary metabolites produced by plants like flavonoids and phenolics illustrate strong anti-inflammatory and antioxidant potentials, which have a significant role in the management of health and disease of human beings.
The current book chapter is focused on the use of plant source of L-DOPA and neuroprotective potential of magical dopa beans and their special prominence in Parkinson’s disease treatment. Along with this we have also focused on the models and other treatments used in treating Parkinson’s disease.
Parkinson’s disease (PD) was initially discovered by Dr. James Parkinson in 1817; it is a chronic neurological disorder triggered by a progressive loss of dopaminergic neurons present in the nigrostriatal part of the brain and found to be common in U.S [12]. In 1970, only few effective drugs were available for treatment of the PD but there is no such therapy yet that completely treats PD. Only thing we can do is to stop the progression of Parkinson’s disease or delay the of PD by replacement of dopaminergic neuron or by mimicking the neuron by using substituent. Management of PD is mainly divided into two categories: first involves improving symptomatic treatment of motor and non-motor types of symptoms and second will be addressing potential causes of PD. Firstly in 1978 Vaidya et al., published the report that PD can be treated by Mucuna extract, a natural source of levodopa having better activity than the synthetic version of levodopa drug [13]. Similar studies were reported in 1990 and 1994 by Kempster et al. and Rabey et al. [14, 15]. L-DOPA is a precursor of dopamine (Figure 1), norepinephrine (noradrenaline), and epinephrine (adrenaline), together known as catecholamines. The dopamine produced cannot cross the blood–brain barrier but L-DOPA can. Outside the brain, L-DOPA can directly be converted to 3-O-methyldopa (3-OMD) by catechol-O-methyl transferase (COM T) and then further to vanillactic acid (VLA), which leads to primary same side effect. To avoid this conversion, standard clinical practices use DOPA decarboxylase inhibitor such as carbidopa or benserazide and often a catechol-O-methyl transferase (COMT) inhibitor [16, 17, 18]. L-DOPA present in Mucuna plant (anti-Parkinson’s drug) [19, 20, 21] helps to produce dopamine. Along with L-DOPA, the reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by Mucuna are stress-producing free radicals playing a great role in the physiological functioning of the body [21, 22, 23, 24, 25, 26, 27, 28, 29, 30]. The content of antioxidant compounds using different solvents in different species of Mucuna, the concentration of antioxidants and other phytochemicals are extremely different. Ethanolic extract of Mucuna seed shows good antioxidant activity due to high phenolic content as compared to methanol, water, and acetone [31]. Some reports also conclude that water is as universal solvent, which shows the significant quantity of phenolic, flavonoids, and strong antioxidants which have the ability to scavenge free radicals using different assays. LCMS (liquid chromatography mass spectrophotometry) report of four different species (Table 1) shows that there are various components like phenolic flavonoids and bioactive compounds present in the Mucuna that are responsible for the production of reactive species [32]. Along with L-DOPA and antioxidants, other secondary metabolites like phenolics, flavonoids, vitamins, enzymes, and protein also have a cumulative effect in the management of PD. Few reports on Mucuna show correlation between L-DOPA, protein, and carbohydrates. The use of plants for the treatment of PD is more beneficial than chemically manufactured L-dopa due to its high potential required in the levo and dextro form purification. It is also studied that various compounds present in Mucuna are responsible for the antimicrobial action, which can be utilized in dealing with various infectious diseases and ulcers [31, 32, 44]. Experiments on various plant pathogens suggest that methanolic extract of Mucuna pruriens seeds showed the highest antimicrobial activity [45]. A similar type of study done by Pujari et al. also determined that methanol extracts of Mucuna pruriens seeds were found to have the best inhibiting activity among all scrutinized pathogens as compared to ethanol and acetone solvents. But alcoholic extract of Mucuna pruriens (L.) leaves has significant antioxidant and antibacterial activity [45]. Dopaminergic agonists or dopamine replacement therapy is a common and most effective way to cure PD. It decreases the signs of disease by sustaining the level of dopamine; however, it cannot regenerate or halt the degeneration. It only replaces or mimics dopamine by inhibiting its breakdown. Apomorphine, bromocriptine, pergolide, piribedil, pramipexole, and ropinirole are some dopaminergic agonists mainly used to heal the PD. All these bioactive compounds present in the Mucuna species have cumulative effect in the treatment of PD. Mucuna pruriens is a species from the Fabaceae family and Faboideae subfamily. M. pruriens is an annual twinning plant in bushes, hedges, and one of the popular medicinal plants indigenous to tropical countries like India [42]. It is useful in relieving inflammation, delirium, neuropathy, cephalalgia, and general debility, nephropathy, dysmenorrhea, amenorrhea, ulcers, constipation, elephantiasis, consumption, helminthiasis, fever, and dropsy. The trichomes of pods contain serotonin and mucunain. The trichomes are used as anthelmintic. Seeds contain glutathione, gallic acid, levodopa (4-3, 4-dihydroxy phenylalanine), lecithin, prurenine, prurenidine, glycosides, nicotine, minerals, and dark brown viscous oil [42].
Synthesis pathway of L-DOPA, dopamine and further metabolites.
Sr.no | Mucuna species | Reference |
---|---|---|
1 | Mucuna imbricata | [32] |
2 | Mucuna macrocarpa | [33] |
3 | Mucuna monosperma | [34] |
4 | Mucuna Bactetia | [35] |
5 | Mucuna sanjepee | [36] |
6 | Mucuna Autripuria | [37] |
7 | Mucuna Latiparica | [5] |
8 | Mucuna prurience | [3, 6, 20, 21, 24, 38, 39, 40, 41, 42, 43] |
9 | M. nigricans | [5] |
10 | M. gigentea | [5] |
11 | Dhanwantari | [5] |
Different species of Mucuna studied till date.
Natural products are valuable sources of bioactive compounds that can be exploited for novel therapeutic potential in PD pathogenesis. There are number of publications reported till now dealing with experiments on hundreds of compounds from various plant species for their different activity in curing the Parkinson’s disease [46]. However, rapid screening of plant-derived natural products and characterization of bioactive compounds is a challenging job. This problem was combated by using Drosophila melanogaster and zebrafish as experimental models at initial stages then followed by studies on various experimental models like, C. elegans, mice/rat, and also cell lines (e.g., murine BV-2 microglia and human SH-SY5Y neuroblastoma cells). Few verdicts using different models are listed underneath.
Drosophila melanogaster, universally familiar as the fruit fly, have turned up as an outstanding model for human neurodegenerative diseases, comprising PD. Due to their high degree of conserved molecular pathways with mammalian models, Drosophila PD models serve to be an inexpensive solution to pilot stages of target validation in the drug discovery pipeline. Fruit fly acts as a screening platform to evaluate the therapeutic potential of phytochemicals from natural extracts against PD [47]. Drosophila melanogaster is a persuasive tool to explore molecular facets and physiopathology of Parkinson’s disease (PD) [48]. There are studies that compare the effects of L-DOPA vs. MP extract using a Drosophila model of autosomal recessive PD in which flies carried a mutation in the PTEN-induced putative kinase 1 (PINK-1) gene [49]. Their observations illustrates that Drosophila fed on MP had a significantly extended lifespan, showed a restored olfactory response and improved climbing behavior compared to flies that consumed L-DOPA.
Owing to its large number of favorable properties, Zebra fish has been used widely as experimental animal for various diseases. Zebra fish are inexpensive, easy to conserve, develop rapidly, and breed in large quantities. Larval zebra fish are also extensively used in toxicity screens since they have a permeable skin through which substances added in the rearing medium are effortlessly taken up. This permits for greater control over dosage and ease of administering substances to large numbers of animals. Furthermore, larval behaviors can be exploited in assays to test the effects of the treatment. Being a vertebrate, the central nervous system of larval zebra fish expressions an extremely homologous to humans. Therefore, toxicology studies performed on larval zebra fish can be very helpful in deciding the putative targets in humans [50]. Thus Danio rerio commonly known as zebrafish is a charming popular animal model for treatments in neuropharmacology and pharmacogenetics. Both the adult and larval zebrafish are presently studied to increase the understanding of central nervous system’s function and dysfunction [51]. There are various studied reports by Gerlai et al. on the latent learning, behavior, and memory alteration of adult zebrafish [51, 52, 53, 54, 55]. Apart from fish, there are several other experimental models.
Many clinical trials have been done on herbal extract and their isolated compound, which has opened a new scenario in the area of PD. The models of PD are induced by different chemical compounds like 6-OHDA, rotenone, and MPTP based on the aim of the experiment. Singh et al. investigated the effect of ethanolic extract of Mucuna pruriens (Mp) on the reduction of oxidative stress level, nitric oxide (NO), and subsequent influence on lipid peroxidation in paraquat (PQ)-induced Parkinsonian mouse model. MTTP-induced Parkinson mouse models were also studied by them for the reduction of estrogen by Mucuna pruriens [26, 55, 56]. Yadav et al. demonstrated that Mp seed extract reduces oxidative stress in nigrostriatal tissue and improves neurobehavioral activity and the expression of tyrosine hydroxylase (TH) in SN and striatum of the brain in PQ-intoxicated mice [56]. Apoptotic pathways of dopaminergic neurons in the PQ mouse model were also found to be inhibited by the neuroprotective activity of Mucuna pruriens [57]. Experiments also reveal that the Mucuna pruriens has a resilient anti-inflammatory property that diminishes the neuroinflammation by plummeting inducible nitric oxide synthase expression in Parkinsonian mice model. Symptomatic and neuroprotective efficacy in rodent model of Parkinson’s disease using Mucuna pruriens seed extract were studied by Kasture and Pontis [58]. Significance of M. pruriens in sperm parameters and sexual behavior of streptozotocin-induced diabetic male rat were studied by Sekar Suresh et al. [59]. Earlier efforts exhibited the capability of Mucuna pruriens seeds extract to induce contralateral turning behavior in the 6-hydroxydopamine (6-OHDA)-lesion persuaded rat model of PD [60]. Likewise, the potential of Mucuna seed powder extract significantly improved activity of brain mitochondrial complex-I without disturbing total monoamine oxidase activity in vitro [61]. Mucuna pruriens also has the potential to amend immune components like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-λ (IFN-λ), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and interleukin-2 (IL-2) in the central nervous system, thereby, averting the progression of dopaminergic neurons degeneration, in PD [62]. Moreover M. pruriens was also assessed for levodopa pharmacokinetics by Sarrafchi et al., in a double-blinded clinical and pharmacological study. They observed that administration of M. pruriens at doses of 2.5, 5.0, or 10.0 g/kg/day for 52 weeks significantly increased the dopamine content of the cortex in animal model of PD. Therefore, they concluded that M. pruriens seed powder with natural source of levodopa probably has benefits over conventional levodopa preparations in treatment of PD due to its longer action and speedy onset without increase in adverse effect [63]. Thus, M. pruriens would seem to be a remarkable commercially viable alternative to standard L-dopa [64]. Likewise, an improvement in motor skills and dyskinesia analogous to those induced by equivalent doses of L-DOPA was also found to be induced by M. pruriens preparations in rat and macaque monkey models of PD [61]. Therefore, all these studies strongly advocate the use of Mucuna pruriens: a treasurable herbal plant for treatment of PD.
Copious studies have scrutinized the effect of MP in PD patients. The bioavailability of L-DOPA in the central nervous system is about one-fifth when pooled with carbidopa or benserazide due to nonexistence of DOPA decarboxylase inhibitor (DDCI) in Mucuna [61, 62, 63, 64, 65]. Even then, the first report in 1978 revealed that 23 PD patients were treated with MP with similar effect and better tolerance than L-DOPA/benserazide. This study was followed by an open study where 60 PD patients in Hoehn and Yahr stage I–IV were treated with MP preparations for over 12 weeks, which led to momentous headways in both UPDRS score and the Hoehn and Yahr stage. This captivated the attention on the registration of Mucuna preparation (Zandopa™) as a treatment for PD in India [61]. Cilia et al. executed a crossover study (N = 14) on PD patients in an advanced stage with motor fluctuations and peak-of-dose dyskinesia. The observations indicated better motor improvement on Mucuna powder consumption in comparison to the effect imparted by intake of an equivalent dose of L-DOPA/benserazide [66]. Innumerable experiments are still under investigation by several assemblages of researchers from all over the world to understand the PD progression and come up with innovative strategies to treat Parkinson’s disease [61, 62].
Gargantuan improvement has been done to treat the PD for over half-century. Diverse individuals from different places have come up with different treatments. Miscellaneous categories of drugs are being used apart from levodopa. Yet to date there are no complete cure strategies for PD. But some symptomatic palliative treatments are being implemented to slow down the disease progression. There are various enzymes used in the management of PD. Enzymes monoamine oxidase-B (MAO-B) and catechol-o-methyl-transferase (COMT) are normally involved in metabolism of dopamine. Therefore, few inhibitors of the two enzymes (MAO-B and COMT) have been extensively studied. Inhibitors like selegiline, rasagiline, tolcapone, and entacapone are being used for the disease modification in PD from previous few years. N-propargyl-methamphetamine is known as selegiline, which is an irreversible inhibitor of MAO-B. Action of selegiline was studied in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in monkeys [67]. It was used at concentration of 10 mg/day, but they found that it loses its selectivity at higher concentrations of dosage [67]. Various other reports show the neuroprotective potential of selegiline but there is no such report proving that selegiline has “disease-modification” effects [68, 69, 70]. The in vitro and in vivo experimental Parkinsonian models indicate that rasagiline (N-propargyl-1-(R)-aminoindan) acted as irreversible MAOB inhibitor exhibiting anti-apoptotic effect [68, 69, 70].
There are various studies proving that the dopamine agonist or levodopa has stronger symptomatic benefits as the MAOB inhibitor; however, there was no evidence of direct comparison between them [71, 72, 73, 74]. Older people provide more rapid onset improvement than younger patients. Dopamine agonist is more prominent in younger people with dyskinesia and older people with orthostatic hypotension and CNS effects (hallucinations). Pharmacokinetic studies revel that COMT inhibitors prevent degradation of peripheral levodopa by extending half-life and also permit it to cross the blood–brain barrier in higher concentrations. There are large number of compounds used to treat motor symptoms and motor complications occurring due to dopaminergic mode of action as reported in review by Oertel et al. Whereas carbidopa (modified form of L-dopa soluble), opicapone (COMT-inhibitor), safinamide (MAO-B-inhibitor), droxidopa (NMDA-receptor antagonist), stradefylline (noradrenaline precursor), tozadenant (Adenosine 2A receptor antagonist), pimavanserin (5HT2A inverse agonist), and donepezil (Acetyl choline esterase inhibitor) are some of the most common compounds used in the treatment internationally [16]. Along with benzhexol and orphenadrine, anticholinergic drugs are also recommended as they reduce the effect of acetylcholine in the brain by antagonizing cholinergic receptors and restore the acetylcholine/dopamine balance within the brain. They also prevent hyperkinesia.
Apart from chemical drugs, there are some physical therapies involved in the treatment of PD that have given special attenuation toward movement (motor) symptoms of patient. In this treatment, parts of the brain involved in the progression of disease are either removed, bombard with electric impulse, or subjected to neuroimaging [75]. In pallidotomy and thalamotomy, the globus pallidus part of the brain, which is overactive in the PD patients, resulting in slackening down the body movements, is surgically destroyed permanently. This destruction of globus pallidus significantly reduces tremor, bradykinesia, balance problems, and writing problems, and eliminates rigidity, while thalamus part is involved in the involuntary movement (like tremor) [76, 77]. Deep brain stimulation (DBS) is also one of the unconventional treatments used, in which brain pace markers (microelectrode) are applied where an electrical impulse passes over the electrodes to the specific part of the brain. DBS decreases the secondary difficulties elevated due to dopaminergic replacement therapy. There are survival disadvantages of pallidotomy and thalamotomy cases due to dysphagia, hypophonia, and dysarthria [78]. DBS is having significant results over thalamotomy because it does not need hardware and have very fewer side effects and relatively lowers the risk of complications. Besides all these pharmacological and surgical treatments, few other strategies like speech therapy, mediations are being currently explored along with it for the treatment of PD. Apart from singular therapy, doctors are now recommending a combination of treatments to impart cumulative effect in the treatment of PD.
Mucuna is a natural, rich source of precursor of dopamine that acts as gold standard for the treatment of Parkinson’s disease to control body movements, hormonal balance, emotion, and memory. The Mucuna is a pharmaceutically and biochemically valuable plant used from the early days, having high market value due to its large amount of bioactive compounds. It also contains a maximum amount of phenolics, flavonoids, and antioxidants, which have a cumulative role in the release of oxidative stress produced by body systems. Drosophila melanogaster, zebrafish, mice/rat, and human models were used to check the potential of Mucuna seed powder on rotenone, MPTP-induced Parkinson’s model, and it was concluded that Mucuna seeds have great values in the treatment of PD. The book chapter also covers various other drugs and neurosurgical treatments used in Parkinson’s disease. It also gives an introduction to various other species (apart from Mucuna FSTA) used in the PD treatment and lowers the burden on commonly used(Mucuna pruriens) species.
IntechOpen publishes different types of publications
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