IgG4-related disease: neurologic manifestations
Nov. 29, 2022
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Management of chronic neurologic diseases requires a multidisciplinary approach. In order for a patient to achieve maximal function, a treatment plan that includes more than just medication should be considered. Outpatient neurorehabilitation services, including physical therapy, occupational therapy, and speech therapy, is an important adjunct to medication treatment of chronic neurologic disease. The ultimate goal of this combined approach is to allow a patient to maintain functional independence.
• Chronic neurologic diseases should be treated with a multidisciplinary approach.
• Clinicians should have a low threshold to refer patients with chronic neurologic disease for neurorehabilitation services.
• Physical therapy, occupational therapy, and speech therapy have roles at time of diagnosis of chronic neurologic disease as well as throughout the course of the disease.
In the United States, physical therapy and occupational therapy emerged as medical professions in 1917 in order to provide rehabilitation to wounded soldiers returning from war (33). Physical therapists employed massage and stretching techniques whereas occupational therapists ran crafting workshops focused on knitting, chair caning, woodworking, printing, or rug making (41). Initially conceived by Congress as a way to decrease the financial burden of the veteran welfare program, rehabilitation medicine was later recognized as an integral component of the healthcare system and has since been utilized by all medical specialties (33).
Language deficits have been described since as early as the late 19th century when poststroke lesional effects on language were identified by Wernicke and Broca (51). As the neurobiology of recovery and learning has become increasingly understood, treatment of language deficits has developed into speech language pathology as we know it today (51).
Physical therapy, occupational therapy, and speech therapy services all have an important role not only in the inpatient hospital setting but also in dedicated acute rehabilitation hospitals, outpatient clinics, and patients’ homes. Neurorehabilitation in particular has become a field unto its own with dedicated training and rehabilitation centers around the country.
Though all chronic neurologic diseases are thought to benefit from neurorehabilitation services, there is limited formal evidence for their use in all but several specific diseases, including stroke, Parkinson disease, traumatic brain injury, and multiple sclerosis. The past few years have also brought an increase in rehabilitation studies focused on other neurologic disorders such as cerebellar ataxias, Huntington disease, functional neurologic disorders, and epilepsy. The COVID19 pandemic has also accelerated the evaluation of tele-rehabilitation and other technology assisted interventions. Despite significant overlap of techniques used to treat all chronic neurologic disease, specialized rehabilitation programs and techniques have been developed to address unique symptoms related to these specific disorders. In all disciplines of therapy, the recommended interventions should be individualized to address specific symptoms or concerns a patient may have. A description of each therapy technique is beyond the scope of this article, which will provide an overall review of the use of neurorehabilitation services and recent advancements.
Physical therapy. The aim of physical therapy is to improve “mobility-related activity,” a term that can refer to transfers, manual activities, posture, balance, and gait (43). Individualized therapeutic approaches may be used to target a patient’s specific limitation or a specific symptom.
Exercise training is a core strategy used by physical therapists in the treatment of neurologic disease. Exercise may include strength training, aerobic activity (such as treadmill or aquatic exercises), and balance training (43). There is a new interest in evaluating high-intensity interval training as an improved exercise regimen in all neurorehabilitation. Active and passive stretching may also be incorporated into the exercise routine. Strengthening of weak muscle groups can be improved with functional weight-bearing or other resistance training (02). Often, an individualized training program can be provided to a patient for ongoing practice at home. Both exercise and physical therapy programs have been shown to be effective in improving symptoms of Parkinson disease, although there may be greater improvement with physical therapy programs than with home exercise programs alone (13; 52). In poststroke gait rehabilitation, combinations of stretching and exercise have been shown to be beneficial as well. For example, repetitive ankle dorsiflexion exercises have been found to improve gait speed and reduce fatigability when alternated with self-stretching (53). Virtual reality and technology assisted rehabilitation is also being increasingly explored as a way to enhance rehabilitation, with one Parkinson disease study showing that outcomes in balance, gait, arm function, and mental aspect of quality of life may be better with virtual reality-based therapy than conventional rehabilitation (40).
A more recent surge in popularity of group exercise programs in Parkinson disease, such as boxing or dance classes, has highlighted the benefit of social interaction on functional outcome as well.
Tango has been shown to improve functional mobility, spatial cognition, and overall well-being in multiple studies (19). Qigong, yoga, and tai chi have all been shown to improve balance, relaxation, and in some cases, improve sleep. External cues during exercise training are particularly helpful for patients with Parkinson disease who have trouble initiating voluntary movement. Visual cues, such as equidistant floor markings (tape) or lasers attached to assistive devices, can provide a visual cue to improve stride length or prevent gait freezing. Rhythmic auditory stimuli can achieve the same effect; metronomes, self-vocalization, and music are examples of effective auditory cues (43).
The Lee Silverman Voice Treatment (LSVT) BIG program was developed in 2005 and is regularly used for the treatment of patients with Parkinson disease. Both bradykinesia (slowness of movement) and hypokinesia (small movement) are characteristic features of Parkinson disease. The focus of LSVT-BIG is to increase the amplitude and speed of movement (35). Movements that are typically performed unconsciously, such as swinging each arm while walking, are purposely exaggerated. Physical therapists are required to have specialized training to administer this protocol. The LSVT-BIG program is considered intensive in that it consists of 16 one-hour sessions over the course of 4 weeks.
Following a stroke, weakness in an individual limb or multiple limbs (such as in hemiplegia) is a significant source of disability for patients. Constraint-induced movement therapy is a technique used to isolate mobility in the affected arm by restraining the unaffected limb (15; 16). Spasticity caused by an upper motor neuron process, such as stroke or multiple sclerosis, may be approached in multiple ways, including exercise therapy, electrical stimulation, vibration, standing therapy, and radial shock wave therapy (18). The use of botulinum toxin for spasticity may help enhance the physical therapy techniques used to improve limb function. In addition, new techniques for improving function in paresis and functional capacity are being explored in physical therapy for all neurologic diseases. These include transcranial magnetic stimulation, functional electrical stimulation (31), brain-computer interface-driven neurorehabilitation (08), powered exoskeleton devices for improved limb function or walking assistance (22), and telemedicine for home physical therapy supervision (11; 44). Clinical trials have shown that virtual reality, robot-assisted therapy, and tele-rehab are feasible and improve upper motor function following stroke but show similar benefits to conventional therapy or recreational activities (48). Similarly, in treatment of multiple sclerosis, noninvasive brain stimulation has been shown to help with pain, urinary symptoms, and lower limb spasticity when combined with traditional rehabilitation therapies (09).
Occupational therapy. Patients with chronic neurologic diseases are often unable to participate fully in domestic, work, or leisure activities due to either a physical impairment or cognitive constraint. The focus of occupational therapy is to improve “self-management” and allow for engagement in activities at home and in the community (43).
The occupational therapist should start by gathering information about the patient’s individualized goals in order to tailor treatment to a prioritized activity. Observation of the activity in the established environment allows the therapist to identify modifiable personal or environmental factors (49). Self-reported surveys are often used to determine functional capacity and to measure outcomes in occupational therapy (14). Newer technology, such as actigraphy, in-home video game rehabilitation, or wearables are being implemented to more accurately evaluate and improve functional performance at home (14; 24).
There are a number of compensatory strategies that may be implemented in occupational therapy to improve a patient’s safety and efficiency during activity. Establishing a structured daily or weekly routine may cue a patient to carry out a particular activity. Other compensatory strategies include focused attention, use of external cues (such as calendars), and use of a simplified or stepwise approach to a particular activity (49). All these strategies may allow a patient to manage the stress that arises from time pressure, unexpected changes in environment, multitasking, or fluctuations in function. The latter is particularly true in patients with Parkinson disease who experience fluctuations in motor control between medication doses or patients with multiple sclerosis who experience significant fatigue (43).
In stroke rehabilitation, many occupational therapy programs focus on impairment-based approaches, which supposes that improvement in the identified impairment will translate into improvement in daily functioning (55). As many studies have shown that patients continue to have impairment in daily tasks despite improvement in their impairment, new approaches, such as “cognitive orientation to daily occupational performance” (CO-OP), instead focus on improving daily function (55). CO-OP involves a strategy to improve performance by implementing a Goal-Plan-Do-Check system that helps promote cognitive flexibility and improvement in motor impairment.
Another important role for occupational therapists is providing guidance on environmental adaptation and use of assistive devices. Strategies for optimizing the home or work environment may include eliminating obstacles (ie, trip hazards, throw rugs), rearranging furniture, modifying the height and support of furniture, or improving lighting (43). Additionally, implementing tools to improve safety, such as grab bars and shower seats, is essential (43). Occupational therapists may perform driving evaluations or provide compensatory strategies and equipment to improve driving safety in the context of physical disability.
As with all disciplines of neurorehabilitation, occupational therapists serve as important educators not only for the patient but also for the caregiver. Occupational therapists may inform caregivers on the expected challenges faced by the patient and provide resources, aids, and environmental adaptations to decrease caregiver burden (43).
Speech therapy. Impairments of language, speech, cognition, and swallowing are common in many of the chronic neurologic diseases, and speech therapists (also known as speech-language pathologists) are trained to address these challenges. The approach to treatment may fall into 1 of 3 broad categories: restorative, compensatory, and supportive techniques (03).
Aphasia is an example of a language deficit that can occur as a result of stroke, a mass lesion, or certain neurodegenerative diseases. Aphasia describes a disorder in which language processing is impaired despite preserved intelligence in many cases. One example of a restorative tool used to treat nonfluent aphasia is melodic intonation therapy in which each syllable of a word or phrase is sung while the clinician taps the patient’s hand (03). Evidence-based, person-centered behavioral therapy is the most commonly used method for treatment of aphasia, allowing patients to gain language function and compensate for residual deficits (51). The addition of transcranial stimulation in speech therapy has also shown promise in treating poststroke aphasia.
When a motor speech disturbance, such as dysarthria, occurs, oral motor exercises are a mainstay of treatment. Biofeedback, such as with the use of tape recorders, can be used to improve not only not volume but also prosody of speech. In the setting of speech apraxia, in which volitional control of speech is impaired, use of automated tasks, such as counting or singing along with repetition of sounds or words, can be useful tools (03).
For all forms of speech or language disorders, communication boards or assistive devices can be used as compensatory strategies while a supportive approach can be used by the conversation partner to increase the patient’s likelihood for success; this may include using yes-no questions and providing adequate time for response (03). Digital rehabilitative programs have been shown to be increasingly used for home therapy following stroke and traumatic brain injury (39).
Specialized speech therapy programs have been developed for particular neurologic diseases. This has been well described in the literature for Parkinson disease. In patients with Parkinson disease, there is a disconnect between a patient’s perceived volume and actual volume of his or her own voice. The Lee Silverman Voice Treatment (LSVT-LOUD) approach to speech therapy in Parkinson disease was developed in 1995 (35). Though the primary goal of the LSVT-LOUD program is to increase speech volume, secondary effects of the program can include improved intelligibility, facial expression, enunciation, and breath support (36). The program is considered intensive as it consists of 16 one-hour sessions over the course of 4 weeks.
Evaluation of dysphagia (impairment of swallowing) begins with an oral motor examination but may require specialized evaluation with a modified barium swallow study or a fiberoptic endoscopic evaluation of swallowing (FEES). Speech therapists often provide recommendations regarding diet consistency but also compensatory strategies such as postural maneuvers to improve swallowing safety. Other compensatory measures may include use of alternate utensils such as straws, repeated swallowing, slowing down the rate of eating, supervision while eating, and limiting distractions (03).
Another area of speech language pathology that is essential for the care of chronic neurologic conditions is cognitive evaluation and therapy. This is particularly important for patients with traumatic brain injury; a cognitive-linguistic assessment should be undertaken for all such patients (28). These types of assessments may evaluate areas of auditory processing, language, and functional cognition. Comprehensive cognitive-linguistic evaluations can help provide a therapist with an understanding of a patient’s ability to function in daily life. For example, the speech language pathology evaluation for patients with mild traumatic brain injury at the Marcus Institute for Brain Health in Colorado evaluates for symptoms of hyperacusis (sensitivity to noise), word-finding difficulties, conversational flow and initiation, disinhibition, executive functioning, attention, reading and writing, visual dysfunction, and verbal memory (28). This battery allows for a complete picture of the impairments faced by patients with mild traumatic brain injury and guides the treatment plan going forward.
Cognitive rehabilitation is increasingly recognized in the care of epilepsy patients (06) The cognitive effects of epilepsy are now widely acknowledged, although trials of interventions to treat the cognitive comorbidities are sparse. There is evidence to suggest that following stabilization of seizures and comorbid psychiatric disorders, neuropsychiatric testing followed by education and cognitive rehab can be useful in patients with epilepsy. This is especially true in those who are undergoing epilepsy surgery. In addition to epilepsy, dementia variants, in particular primary progressive aphasia (PPA), benefit greatly from cognitive rehabilitation (54). Semantic and phonologically-based word retrieval strategies can show immediate gains in patients with progressive aphasia. Other strategies that have shown benefit include script training for fluency and facilitative behaviors for communication.
Other rehabilitation treatments. Depending on the location of a stroke or brain injury, various other cortical symptoms can occur, such as vision changes and neglect. Vision or ocular rehabilitation can be utilized to help poststroke patients with these chronic impairments. One such treatment is the prism adaptation, where patients complete daily visuomotor training sessions while wearing prisms to improve symptoms of neglect (25). However, prism adaptation treatment length is still being studied to determine the feasibility in an outpatient setting. In addition, larger randomized studies are also needed to evaluate the benefit of vision therapy beyond the natural course of recovery in disorders such as traumatic brain injury (05).
Music therapy is an area that is being more frequently studied in multiple neurologic diseases. In particular, enhancement of the motor control through music has been an active area of research in multiple sclerosis, stroke, and Parkinson disease. Interventions to enhance neurologic function through music can either be passive (listening) or active (playing or producing music) (26). One example of this is music-supported therapy, where stroke patients are taught to play an instrument with their effected upper limb to improve both fine and gross motor movements (26). In both stroke and Parkinson disease, music-based rhythmic gait training has been shown to improve cadence, step length, and gait speed (17; 30).
Another area of focus that influences rehabilitation for patients with chronic neurologic disorders is psychological or behavioral treatment. Depression and anxiety are common comorbidities in disorders such as Parkinson disease, stroke, traumatic brain injury, and multiple sclerosis. However, studies have shown various treatments and timelines for psychological management of chronic neurologic disorders with no set guideline for the management of these comorbidities in long-term neurorehabilitation. For example, a systematic review of behavioral therapies in posttraumatic headache and postconcussive syndrome found that published interventions are heterogeneous and include cognitive behavioral therapy, group therapy, telephone therapy, psychoeducation, and cognitive training to name a few (37). Psychological distress has also been shown to have an inverse relationship to functional improvement in poststroke patients, emphasizing the importance of addressing psychological symptoms during rehabilitation (29). Additionally, treatment of poststroke depression with either citalopram or cognitive behavioral therapy along with rehabilitation showed greater benefit in depression scales than rehabilitation alone, despite prior evidence that rehabilitation alone can treat stroke-related depression (23).
Multidisciplinary clinics. For many neurologic conditions, multidisciplinary clinics are being increasingly utilized. These clinics include physical therapy, occupational therapy, speech therapy, and physician evaluations all within 1 patient visit. This model resembles the structure of acute inpatient rehabilitation and has been shown to be an efficient way to provide patients with comprehensive rehabilitation services. The effectiveness of this model relies on the improved communication between specialists, which can increase the efficiency of care, provide cohesive care, improve outcomes, and ultimately reduce the cost of care (28). To date, multidisciplinary clinics have been shown to be beneficial in stroke, chronic migraine, multiple sclerosis, traumatic brain injury, Huntington disease, and spinal cord injury (32). A key component of multidisciplinary care for patients with neurodegenerative diseases is also education for the patient and the caregivers. This has been recommended for diseases such as Huntington disease, where caregiver training was highlighted as an important way to maintain exercise programs long term (42). In the setting of the COVID19 pandemic, many neurorehabilitation centers transitioned to tele-rehab. Spaulding rehabilitation center in Massachusetts found that patient satisfaction was high for a synchronous tele-rehabilitation program that provided physical therapy, occupational therapy, and speech therapy within the same tele-rehabilitation visit (50).
There are no defined criteria available to guide referral for rehabilitation services. Providers should have a low threshold to refer patients with chronic neurologic disease to outpatient rehabilitation services. There is a role for neurorehabilitation regardless of the typical course of a disease, whether that be slowly progressive, as in Parkinson disease, or episodic, as in relapsing remitting multiple sclerosis. There is some evidence that factors such as age and time to outpatient therapy may improve rehabilitation outcomes, but there are no specific guidelines for which patients will benefit from certain outpatient therapy or when therapy initiation is most beneficial (34). It is, therefore, generally accepted that rehabilitation should be initiated regardless of stage of a progressive disorder or characteristics of the patient. This is in part due to the role of rehabilitation to not only improve impairments (which have been shown to be modest in the case of stroke) (34), but also to maintain function and prevent complications related to a chronic neurologic disease.
There are no known exclusion criteria for involvement in speech or occupational therapy. Because exercise is often incorporated into the treatment paradigm of physical therapy, certain patients may be excluded from this form of neurorehabilitation. Patients with chronic neurologic syndromes may have comorbid medical diseases that prohibit involvement in strenuous physical activity. Formal exercise testing may be indicated in patients with heart failure, exertional dyspnea, chest pain, or known arrhythmias (27).
Pregnancy itself is not a contraindication to participation in outpatient physical therapy though consultation with an obstetrician prior to initiating therapy should be considered. According to the 2015 guidelines published by The American College of Obstetricians and Gynecologists, the following are absolute contraindications to aerobic exercise in pregnancy: hemodynamically significant heart disease, restrictive lung disease, incompetent cervix or cerclage, multiple gestation at risk of premature labor, persistent second- or third-trimester bleeding, placenta previa after 26 weeks of gestation, premature labor during the current pregnancy, ruptured membranes, preeclampsia or pregnancy-induced hypertension, and severe anemia (04).
Although the goal of all neurorehabilitation is to improve function, some patients may only be capable of maintaining their current level of function. Though rehabilitation interventions are thought to be beneficial for all chronic neurologic diseases, outcome measures are only recently being collected for outpatient therapy (34). Furthermore, randomized control trials of interventions are sparse and limited to only certain neurologic conditions, which will be highlighted below.
Outcome data regarding rehabilitation in chronic neurologic disease largely come from the field of stroke, where early rehabilitation has been shown to greatly improve function and reduce the risk of recurrent stroke (10). Studies are now focusing on the combination of inpatient and outpatient stroke rehabilitation. Chang and colleagues have shown that in Taiwan, outpatient rehabilitation alone or following inpatient rehabilitation greatly reduced the risk of recurrent vascular events, readmission, and mortality for an average of 32 months (10).
Functional limb overloading training has been evaluated in community-dwelling stroke patients in a 4-week outpatient trial (02). Patients underwent task-oriented gait training for 1 hour 3 times per week while wearing a weighted cuff. The study found that functional limb overloading improved gait performance, weight-bearing ability of the stroke-affected limb, perceived mobility, and community participation.
Treadmill training has also been implemented in chronic neurologic diseases to improve gait and motor function. A phase 2 clinic trial demonstrated that high intensity treadmill exercise in de novo patients with Parkinson disease resulted in a slower rate of decline in motor function when compared to moderate intensity exercise or usual care (45; 52). Exercise can not only improve mobility and physical endurance but also may improve nonmotor symptoms (in particular, depression and cognitive function) in patients with Parkinson disease (19). Similarly, a randomized control trial of high intensity treadmill training in poststroke patients showed greater improvements in the 6-minute walk test and 10-meter walk test as well as in stride length, step length, and cadence (38).
Focused trials on outcomes of occupational therapy are limited. That being said, a 2014 randomized controlled trial comparing home-based occupational therapy to standard care in patients with Parkinson disease demonstrated improvement in self-perceived performance in daily activities as measured by the Canadian Occupational Performance Measure (COPM) (49). Similarly, a study in stroke patients assessing upper extremity improvement found that improvement in functional capacity (ability to use the arm) does not always correlate to functional performance at home as measured by an accelerometer (14). The authors supported the use of performance-based assessments such as the COPM and suggest that accelerometry may be a clinically feasible way to further capture patient performance following therapy.
The beneficial effects of the LSVT-BIG and -LOUD programs have been extensively studied. When compared to a shorter format physical therapy program or general exercise, the standard LSVT-BIG program has been shown to significantly improve motor function as measured by the Unified Parkinson Disease Rating Scale (UPDRS) (35). LSVT-LOUD has been shown to improve volume of speech even 2 years following treatment, and a study demonstrated improvements in both cough control and swallowing function that were sustained for 6 months posttreatment (36).
In chronic poststroke aphasia, there has been debate regarding the level of intensity of speech language therapy (47). Reviews have shown 5 to 10 hours of speech therapy per week, or moderate intensity therapy, will lead to improvement in standard evaluations of aphasia. A study on intensive language action therapy, which is an expanded version of constrained-induced aphasia therapy for over 10 hours per week, did not show benefit over moderate-intensity therapy. The authors, therefore, recommend that 2 hours per day of speech therapy is sufficient to improve poststroke aphasia by standard measurements (47).
The effects of a multidisciplinary approach on outcomes in other neurologic disorders have also been demonstrated. A systematic review of multidisciplinary therapy in Huntington disease demonstrated improvement in motor function, gait speed, and balance along with improved quality-of-life-scores (21). The HEROs trial sought to further define the benefit of multidisciplinary therapy in patients with Huntington disease. Following 36 weeks of supervised exercise training, a home exercise program, and cognitive therapy, participants demonstrated improved hand dexterity and leg strength (12).
Similarly, multidisciplinary clinics have also been shown to improve chronic, refractory headache patient outcomes. Using a 3-week, outpatient, interdisciplinary program, Krause and colleagues demonstrated a significant decrease in headache severity, disability, and psychological distress both at discharge from the program and at 1 year follow up (32).
When resources allow, it is important to refer patients to therapists who have had advanced training in treatment of neurologic diseases. Within the realm of physical therapy, referral to specialized therapists can help to mitigate risk for adverse events including falls or stretch injury. Education of a patient’s caregiver throughout the course of therapy is equally important not only to ensure adherence to an exercise program at home but also to decrease risk of injury to the patient.
Patients with Parkinson disease and related disorders often develop associated autonomic instability. This can manifest in the form of neurogenic orthostatic hypotension, which leads to an, at times, dramatic drop in a person’s blood pressure after standing from a seated or supine position. Symptomatic orthostatic hypotension may limit a patient’s ability to safely participate in exercise, and consultation with the patient’s provider may be required prior to initiation of rehabilitation services, particularly physical therapy.
The following is a factitious case.
Mr. N was a 79-year-old man with Parkinson disease who presented to his neurologist for follow-up in clinic. He was diagnosed with Parkinson disease 6 years prior, with presenting symptoms that included stiffness, decreased dexterity, and resting tremor in the right hand. He had been maintained on carbidopa-levodopa for the past 4 years with improvement in his tremor and rigidity, but he had unfortunately been noting increasing motor fluctuations in recent months. Despite taking his carbidopa-levodopa every 3 hours, he was experiencing wearing-off of the medication. He also reported freezing of gait, which could occur both during the “on” and “off” periods between medication doses. He had particular difficulty making turns or crossing thresholds when moving from 1 room to another, and he had several falls resulting from these freezing episodes.
His neurologist opted to refer Mr. N to outpatient physical therapy with particular attention on gait training and fall prevention. Mr. N established care with a physical therapist who had specialized training in treating patients with Parkinson disease. He attended 12 therapy sessions in total. During these sessions, treadmill exercise, lower extremity strength training, and balance exercises were incorporated. He learned how to use a metronome while walking to help slow down his steps and prevent freezing. He was also instructed on how to create visual cues at home by taping the floor, particularly around corners.
At his next clinic visit, Mr. N reported that he had experienced no falls since his last appointment. He was pleased to report that he had continued practicing the techniques he learned in physical therapy during home exercise sessions. On gait assessment, he had noticeably increased arm swing and stride length, and he took a wide turn without freezing.
Regeneration of the adult central nervous system after injury was once thought to be limited. Thanks to the advent of functional imaging and magnetic resonance technology in recent decades, there has been a paradigm shift in the scientific community toward an understanding of neuroplasticity. According to a paper by Dr. Mary L Dombovy, CNS plasticity is thought to arise from a combination of factors including “neurogenesis, programmed cell death, dendritic and axonal sprouting, long-term potentiation and long-term depression of synaptic transmission, and recruitment of the adjacent cortex and the contralateral hemisphere” (15; 16). Rehabilitation services, therefore, aim to enhance neuroplasticity to reduce functional impairment.
The scientific rationale for neurorehabilitation largely stems from research studying the effects of physical therapy. In the Parkinson disease population specifically, researchers have demonstrated that treadmill exercise increases D2 receptor binding potential (20) whereas balance training may lead to changes in grey matter (46). Through functional MRI imaging, researchers have also shown that rhythmic auditory cues used in exercise training for patients with Parkinson disease may help to recruit compensatory neural networks (07). Transcranial magnetic stimulation studies during treadmill exercise in Parkinson disease has shown normalizing of corticomotor excitability (19). Exercise is also thought to contribute to neuroplasticity through increased neurotransmitter synthesis and decreased oxidative stress (01). In aphasia research, theories on brain organization and reorganization influence meaningful therapy goals and support early and intense therapy initiation (51).
All contributors‘ financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
All contributors‘ financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Stephanie Bissonnette MPH DO
Dr. Bissonnette of Boston University Medical Center has no relevant financial relationships to disclose.See Profile
Peter J Koehler MD PhD
Dr. Koehler of Maastricht University has no relevant financial relationships to disclose.See Profile
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