Afferent pathways

Functionally, the basal nuclei can be divided into an afferent portion and an efferent portion ( Fig. 18.2 ). The afferent structures are the caudate and putamen. They receive input from the entire cerebral cortex, the intralaminar thalamic nuclei, and the centromedian-parafascicular complex of the thalamus as well as from the substantia nigra and the dorsal raphe nucleus, both located within the brain stem. The projections from the cortex are systematically arranged so that the frontal cortex projects to the head of the caudate and putamen and the visual cortex projects to the tail. In addition, the prefrontal cortex projects mainly to the caudate, whereas the sensorimotor cortex projects mainly to the putamen. Projections from the cortical regions that represent the proximal musculature, and those from the premotor regions, may be bilateral. ^, These close and profuse connections between the cortex and the basal nuclei suggest a close interfunctional relationship. The projections from the thalamus to the caudate-putamen are also somatotopically arranged. The heaviest projections are from the centromedian nucleus, and these nuclei also receive massive input from the motor cortex. ^,

Afferent and efferent portions of the basal nuclei.

The somatotopic arrangement of the cortico-striatal–thalamic-cortical pathways is maintained throughout the loop. This finding has led to an important functional hypothesis that the basal nuclei form parallel pathways subserving specific sensorimotor and associative functions. The putamen is linked to the sensorimotor functions and the caudate to the associative, including cognitive functions. ^,

As knowledge of the circuitry of the basal nuclei has advanced, so has the knowledge regarding the microscopic structure. The caudate-putamen looks somewhat homogeneous because of the predominance of one cell type. Careful analysis using precise staining methods has demonstrated the appearance of patches within these nuclei. It is hypothesized that this organization is important for the ability of the basal nuclei to modulate ongoing sensory input and choose the appropriate motor response. The intrinsic structure of the caudate-putamen also suggests that at least nigral input occurs in a way that could immediately modulate the input coming from the cortex. ^,

Efferent pathways

The input that has been processed in the caudate-putamen is sent to the globus pallidus (pallidum) and substantia nigra (nigra), which constitute the efferent portion of the basal nuclei. The globus pallidus and substantia nigra are each divided into two regions. The globus pallidus has an external and an internal region; the substantia nigra consists of the dorsal pars compacta and the ventral pars reticulata. Embryologically and microscopically, the internal segment of the globus pallidus and the pars reticulata of the substantia nigra are similar. These two regions are the primary efferent structures for the basal nuclei. The projections from the caudate and putamen to the pallidum and nigra maintain a somatotopic arrangement. ^{, ,} From these structures the information is transmitted to the thalamus and then to the cortex, still maintaining somatotopy. The superior colliculus, the PPN, and other, less-defined brain stem structures (perhaps the reticular formation) also receive pallidal and nigral output. All output of the basal nuclei has then been processed through the globus pallidus and/or the substantia nigra before proceeding to other areas of the brain (see Fig. 18.2 ).

Pathways to the motor system

Information processed in the basal nuclei can influence the motor system in several ways, but no direct pathway to the alpha or gamma motor neurons of the spinal cord exists. The first route is the projection to the ventroanterior and ventrolateral nuclei of the thalamus, which then project predominantly to the premotor cortex. Another pathway is through the superior colliculus and then to the tectospinal tract. Pathways exist from the globus pallidus and substantia nigra that terminate in areas of the reticular formation (e.g., the PPN) and therefore may influence the motor system through the reticulospinal pathways. Research also supports the connection of the basal nuclei and the cerebellum and thus these two regions of the brain have the opportunity to further integrate movement responses. This includes support for the cerebellar-basal nuclei connection contributing to the Parkinsonian tremor and dystonia.

The basic circuitry of the basal nuclei comprises two loops. The loops for the sensorimotor system are shown in Fig. 18.3 . The direct loop is the loop that begins in the motor regions of the cortex and projects to the putamen and then directly to the globus pallidus, the internal segment, and on to the thalamus. The indirect pathway adds the subthalamic nucleus between the globus pallidus, external segment, and internal segment before sending the signal on to the thalamus. The subthalamic nucleus also receives direct input from the premotor and motor cortex as well as from the pallidum. ^, The darkened neurons represent inhibitory connections, and the open neurons represent excitatory connections. In general, the direct pathway, by disinhibition, activates the thalamocortical pathway; the indirect pathway inhibits the thalamocortical system. The role of these loops in normal and diseased states is clarified in the discussion of the physiology and pharmacology of the basal nuclei.

Diagram of the sensory motor portion of the basal nuclei depicting the direct and indirect pathways. Black circles represent inhibitory neurons; open circles represent excitatory neurons. CM , Centromediannucleus of the thalamus; GPe , globus pallidus external segment; GPi , globus pallidus internal segment; MC , motor cortex; PMC , premotor cortex; SMA , supplementary motor cortex; SNr , pars reticularis of the substantia nigra; STN , subthalamic nucleus; VApc/mc , ventral anterior pars parvocellularis and pars magnocellularis of the thalamus; VLo , ventral lateralis pars oralis nucleus of the thalamus.

(Reprinted from Alexander GE, Crutcher MD. Functional architecture of basal nuclei circuits: neural substrates of parallel processing. Trends Neurosci. 1990;13:266–271.)

In summary, input from the motor cortex, all other areas of the cortex, parts of the thalamus, and the substantia nigra enter the basal nuclei through the caudate and putamen. Here they are processed and sent on to the globus pallidus and substantia nigra. The appropriate “gain” of the system is adjusted, for example, how large a movement is necessary or how much postural stability is needed. The information is sent to the muscles by way of the thalamus and motor cortex, the superior colliculus, and/or the reticular formation.

Automatic movement

The earliest view of the basal nuclei came from Willis in 1664. He hypothesized that the corpus striatum received “the notion of spontaneous localized movements in ascending tracts … Conversely, from here tendencies are dispatched to enact notions without reflection [automatic movements] over descending pathways.” Willis possessed great insights in the discussion of the signs and symptoms of basal nuclei disease. Magendie in 1841 demonstrated that removal of the striatum bilaterally produced compulsive movements, whereas removal of only one striatum produced no visible effect. Studies by Nothnagel demonstrated that lesions of the nigra tended to produce immobility. With the advent of the use of electrical stimulation in the late-19th century, further information on the function of the basal nuclei was gathered. Stimulation of the caudate nucleus did not (and does not) produce movement of muscles or limbs, as occurs with stimulation of the motor cortex; however, at higher levels of current, total-body patterns and postures were usually evoked. The earliest stimulation of the caudate nucleus produced an increase of flexion of the head, trunk, and limbs and tonic contraction of the facial muscles. These early studies are mentioned because of the insights they provide for the symptoms of the disorders of today.

Motor problems in animals

Contemporary experiments using lesion paradigms show a wide variety of motor problems in a variety of animals. Hypokinesia, a decrease or poverty of movements, a decreased amount of exploration of novel environments, and a tendency to assume a fixed posture are the most common problems after a lesion in the basal nuclei. These motoric dysfunctions are seen regardless of the method by which the lesion is made: pharmacological, surgical, or by stimulation. In essence, movements are altered in scale (related to the gain), take longer for completion, and take place under altered conditions of antagonistic muscle interactions (e.g., contraction).

Movement initiation and preparation

The hypothesis that the basal nuclei are involved in movement initiation and preparation has been an area of some research disagreement. A “readiness potential,” recorded from the scalp of human beings before movement and thought to reflect basal nuclei activity, is more apparent in complex than in simple movements, for example, before dorsiflexion with gait but not before dorsiflexion when sitting.

Neuronal recordings from awake, behaving animals found that units in the basal nuclei alter their activity before changes in the electromyographic activity of the prime movers of the task. Studies recorded from multiple units in animals moving freely in their home environment suggest that neurons in the caudate-putamen and in the substantia nigra are activated in sequential, purposeful movements. More recent functional magnetic resonance imaging (fMRI) studies emphasize the role of the mesial premotor cortex and its role as part of the cortico-basal nuclei-thalamo-cortical network for motor planning and movement initiation. This includes the role of the substantia nigra during motor planning caused by the dopaminergic gating of motor sequences.

Postural adjustments

The basal nuclei have been implicated in the process of posture and postural adjustments. People with diseases of the basal nuclei assume flexed or other fixed postures as the disease progresses ( Fig. 18.5 ). In addition, these individuals have decreased postural stability and are therefore at risk for falls. Animal experiments indicate that a deficit exists in determining response based on one’s own body position, or “egocentric localization.” This deficit decreases the ability of a person with basal nuclei disease to modify a postural response to the precise environmental demands.

Typical posture of a patient with Parkinson disease from the front (A) and from the side (B) . Note the flexed spine, mild flexion at the hips and knees, and excessive dorsiflexion with weight predominantly on the heels. Patient was at Hoehn and Yahr stage 2.5.

Martin, in his extensive studies of individuals with Parkinson disease, was the first to describe severe disturbances in posture, especially when vision was occluded. Melnick and colleagues showed that a decrease in static postural adjustments in persons with Parkinson disease could be seen early in the disease process. Bloem and colleagues and Visser and colleagues meticulously studied the reflexes involved in postural adjustments and described deficits in the longer loop reflexes but not in the short latency reflex associated with the stretch reflex.

Others have investigated the interactions of the sensory systems involved in balance in those with Parkinson disease. Bloem and colleagues and Visser and colleagues concluded that postural instability was caused by a decrease in proprioception. In a recent review of proprioception and postural stability and motor control, Nicola and colleagues also describe the kinesthetic and proprioceptive deficits in people with Parkinson disease. Nicola and colleagues concluded that there was a “failure” in the body map similar to the failure in egocentric localization described previously. ^, A decrease in the ability to use proprioceptive and kinesthetic information to properly scale the input and response also contributes to a loss of balance reactions.

Perceptual and cognitive functions

The basal nuclei are not solely motor systems. The previous paragraphs demonstrate the role of the basal nuclei in sensory integration, but they are also involved in cognitive functions and responses associated with reward. ^{, , , ,} Researchers have found that learned movements are more affected by basal nuclei lesions than reflexes, neurons in the basal nuclei are responsive to some sensory input, especially proprioceptive input, and neurons in other parts of the basal nuclei are responsive to reward and anticipation of the reward. ^{, ,} Klockgether and Dichgans, as well as Jobst and colleagues, found that patients with Parkinson disease likewise had impairments in kinesthesia and that as a person moved a limb further from the body’s center, kinesthetic sense decreased. Schneider and colleagues found that animals that developed parkinsonian symptoms from a neurotoxin had deficits in operantly conditioned behavior. They suggested that the decrease in performance resulted from a “defect in the linkage” between a stimulus and the motor output centers. These sensory difficulties may be important factors in evaluation and treatment of basal nuclei diseases, especially those associated with dystonia.

The basal nuclei appear to be involved in the process of withholding a response until it is appropriate. A deficit in alternation of response may be the result of a tendency toward perseveration of a previously reinforced cue. Additional deficits exist in remembering or relearning tasks requiring a temporal sequence. Graybiel integrated the behavioral findings with information from her anatomical and chemical studies to suggest that the basal nuclei are important in providing behavioral flexibility. She hypothesizes that the basal nuclei are involved in procedural learning that leads to the development of habits. These habits become routine and are easily performed without conscious effort; we are free to react to new events in our environment and to think. Graybiel and colleagues have performed electrophysiological experiments that explain this learning process, and these studies demonstrate great plasticity in basal nuclei networks. ^, This enables the individual to select the proper movements in the proper environmental context. These cognitive dimensions are important to remember when developing a plan of care for a patient with basal nuclei dysfunction.

The ability to perform cognitive activities involves integrating sensory information and, on the basis of this information, making an appropriate response. Humans with basal nuclei disease may show problems in perceptual abilities, including deficits in tasks that involve perception of interpersonal and intrapersonal space. The basal nuclei seem to have a sensory integrative function as evidenced by experiments that show a multisensory and heterotopic convergence of somatic, visual, auditory, and vestibular stimuli. ^, Segundo and Machne, ^, as well as Nicola and colleagues, hypothesized that the function of the basal nuclei was not subjective recognition of the stimuli but rather in the regulation of posture and movements of the body in space and in the production of complex motor acts.

For movements to be properly controlled and properly sequenced, the two sides of the body need to be well integrated. There is anatomical evidence that suggests some means of bilateral control for the basal nuclei. A lesion of one caudate nucleus or nigrostriatal pathway produces a change in the unit activity of the remaining caudate. ^, Studies of the dopaminergic pathway also indicate interactions between the two sides of the body. For this reason one may find deficits in function even on the “uninvolved” side of an individual with disease or lesion of the basal nuclei. It is also possible that diseases of the basal nuclei may go unnoticed until damage is found bilaterally.

This summary of experimental results on the function of the basal nuclei illustrates several points. At least in some general way the basal nuclei are involved in the processes of movement related to preparing the organism for future motion and future reward. This may include preparing the cortex for approximate time activation, setting the postural reflexes or the gamma motor neuron system, organizing sensory input to produce a motor response in an appropriate environmental context, and inhibiting all unnecessary motor activity. Owing to the multilevel involvement of the basal nuclei in movement, it is crucial that clinicians carefully observe all aspects of movement (simple and complex) with and without interference of sensory cues or performance of dual tasks as well as postural tone during examination, treatment, and the responses to treatment.

Symptoms

Gait.

The typical Parkinsonian gait is characterized by decreased velocity and stride length. As a consequence, foot clearance is decreased, which places the individual at a greater fall risk. In many patients, especially as the disease progresses, speed and shortening of stride progressively worsen as if the individual is trying to catch up with his or her center of gravity; this is termed festination. Forward festination is called propulsion; backward festination is known as retropulsion. One hypothesis is that festinating gait is caused by the decreased equilibrium responses. If walking is a series of controlled falls and if normal responses to falling are delayed or not strong enough, then the individual will either fall completely or continue to take short, running-like steps. The abnormal motor unit firing seen with bradykinesia may also be the cause of ever-shortening steps. If the motor unit cannot build up a high enough frequency or if it pauses in the middle of the movement, then the full range of the movement would decrease; in walking this would lead to shorter steps. Festination may also be the result of other changes in the kinematics of gait.

The changes in gait kinematics include changes in excursion of the hip and ankle joints ( Fig. 18.7 ). Instead of a heel-toe, the patient may have a flat-footed or, with disease progression, a toe-heel sequence. The flat-footed gait with poor weight shifting decreases the ability to step over obstacles or to walk on carpeted surfaces. The use of three-dimensional gait analysis has shown that there is a decrease in plantarflexion at terminal stance. Changes are also seen in hip flexion, which may alter ankle excursion; however, qualitative aspects of the timing of joint excursion appear intact. Fig. 18.7 illustrates the joint angles in a 55-year-old patient with Parkinson disease compared with adults without basal nuclei dysfunction.

Angles of Excursion During Gait in a Patient With Parkinson Disease.

Shaded areas are mean ± standard deviations for adults without Parkinson disease; black lines represent a patient with Parkinson disease. Movement shown for right- and left-lower extremities. Note decreases, especially in left lower extremity for extension and bilateral decreased plantarflexion.

Impaired gait and postural instability are the two impairments that contribute to the greatest activity limitations to persons with Parkinsonism. The inability to ambulate safely and the high fall risk of these patients are the major elements contributing to mortality and preventing independence in home and work as the disease progresses.

Stages of Parkinson disease

Staging of Parkinson disease uses the Hoehn and Yahr scale ( Table 18.1 ). Originally developed as a 5-point scale, in recent years 0, 1.5, and 2.5 measurements have been added. The 1.5 and 2.5 ratings have not been validated, but because their use is so common, the latest recommendation is to continue using them while the validity is studied.

In stage 1 of the disease, initial motor symptoms, often a resting tremor or unilateral micrography (bradykinesia of the upper extremity), is present. Stage 2 progresses with rigidity and bradykinesia bilaterally, and postural alterations and axial symptoms begin to occur. This commonly starts with an increase in neck, trunk, and hip flexion that, accompanied by a decrease in righting and balance responses, leads to a decreased ability to maintain the center of gravity over the base of support.

While these postural changes are occurring moving into stage 3, so does an increase in rigidity, which is most apparent in the trunk and proximal and axial musculature. Trunk rotation becomes severely decreased; there is no arm swing during gait and no spontaneous facial expression; and movement becomes more and more difficult to initiate. Movement is usually produced with great concentration and is perhaps cortically generated, thereby bypassing the damaged basal nuclei pathways. This great concentration then makes movement tiring, which heightens the debilitating effects of the disease, requiring assistive devices to ambulate in stage 4.

Eventually the individual becomes wheelchair bound and dependent. In the late and severe stages of the disease, especially without therapeutic attention for movement dysfunctions, the patient may become bedridden and may demonstrate a fixed trunk-flexion contracture regardless of the position in which the person is placed. This posture has been called the “phantom pillow” syndrome because, even when lying supine, the person’s head is flexed as if on a pillow.

Throughout this progressive deterioration of movement, there is also a decrease in higher-level sensory processing. In addition, the patient can perform only one task at a time. Reports of dementia range from 30% to 93% in patients with Parkinson disease. The presence of dementia in this population may indicate involvement of the ACh or noradrenergic mesolimbic system. In this case, treatment with anticholinergic drugs may increase a tendency toward dementia, especially in older patients. Sometimes, cognitive deficits are inferred because of slowed responses, spatial problems, sensory processing problems, and a masked face.

The most serious complication of Parkinson disease is bronchopneumonia. Decreased activity in general and decreased chest expansion may be contributing factors. Aspiration pneumonia can also contribute to mortality because patients may experience dysphagia and dysarthria. The mortality rate is greater than in the general population, and death is usually from pneumonia.

Pharmacological considerations and medical management

The knowledge that the symptoms of Parkinson disease are caused by a decrease in DA led to the pharmacological management of this disease. Because DA itself does not cross the blood-brain barrier, levo-dihydroxyphenylalanine (l-dopa), a precursor of DA that does, has been used to treat Parkinson disease since the late 1960s. ^, An inhibitor of aromatic amino acid decarboxylation (carbidopa) is usually given with l-dopa to prevent the conversion to DA before entering the brain. The decarboxylase inhibitor allows a reduction in dosage of l-dopa itself, which helps decrease the cardiac and gastrointestinal side effects of DA.

Amantadine is another drug that has been effective in the treatment of patients with Parkinson disease. Although the mechanism of action of this antiviral medication is unknown, it is thought to include a facilitation of release of catecholamines (of which DA is one) from stores in the neuron that are readily releasable. It is often administered in combination with l -dopa.

Treatment of Parkinson disease with l -dopa in these various combinations is extremely helpful in reducing bradykinesia and rigidity. It is less effective in reducing tremor and the postural instability. Because Parkinson disease involves the nigral neurons, the receptors and the neurons in the striatum (which are postsynaptic to dopaminergic neurons) remain intact and, initially, are somewhat responsive to DA. ^, With time, however, the receptors appear to lose their sensitivity, and the prolonged effectiveness (10 years or more) of l -dopa therapy is questionable. A further complication of l -dopa therapy is the development of involuntary movements (dyskinesias) and the “on-off” phenomenon—a short-duration response resulting in sudden improvement of symptoms followed by a rapid decline in symptomatic relief and perhaps the appearance of dyskinesias and/or dystonias. ^, With time the “on” effect becomes of shorter and shorter duration. ^{, , ,} Controlled-release or slow-release l -dopa may decrease these side effects. The effectiveness of l -dopa does not appear to be closely correlated with the stage of the disease.

The use of l -dopa alone or in combination with carbidopa has not provided a cure or even prevented the degeneration of Parkinson disease. ^, As more has become known about the DA receptor, specific agonists have been developed. Ropinirole, pramipexole, pergolide, and bromocriptine are examples of DA receptor D2 agonists that are used alone or with l -dopa. The agonists are thought to decrease the wearing-off effects as well as decrease the dyskinesias that occur with long-term l -dopa use, but l -dopa remains the most effective medication. It is quite likely that newer D2 and/or D2-D1 (DA receptor D1) agonists will be developed. Pharmacological interventions also include drugs that prevent the breakdown of DA (e.g., catechol- O -methyltransferase [COMT] inhibitors) and/or its reuptake. Entacapone is an example of a COMT inhibitor.

Another approach to pharmacological treatment of individuals with Parkinson disease was developed from research on a designer drug that contained the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was found that the conversion of MPTP to the active neurotoxin MPP+ could be prevented by monoamine oxidase inhibitors such as deprenyl and pargyline. ^, Deprenyl, rasagiline, and selegiline are now used before the initiation of, or in conjunction with, l -dopa and carbidopa.

Another treatment alternative is surgery performed in precise areas of the basal nuclei, known as stereotaxic surgery. Stereotaxic surgery is an old technique that has made a comeback based on the new knowledge of basal nuclei connectivity and improvements in the procedural instrumentation. Initially, one of the structures of the basal nuclei was lesioned with freezing or high-frequency stimulation. Today, the globus pallidus internal segment or the subthalamic nucleus is stimulated with implanted electrodes. This technique is known as DBS. DBS has now been approved by the US Food and Drug Administration (FDA). An advantage of DBS over permanent lesions is that DBS is reversible and is safer for bilateral surgeries. Stimulation of the globus pallidus internal segment or subthalamic nucleus has been shown to decrease all symptoms; subthalamic nucleus stimulation is also effective in reducing dyskinesias and may lessen the amount of medication taken. Effects of stimulation are greater for symptoms manifested in the “off” state. DBS has been demonstrated to improve rigidity, bradykinesia, and akinesia, as well as gait ^, and balance. ^, It has also been demonstrated to improve movement velocity and speed of muscle recruitment for activity. ^, The proposed mechanism of action is interference with the abnormal neuronal firing. ^, In a randomized, controlled clinical trial, DBS was more effective in reducing symptoms and increasing quality of life than medication. ^, This group also found that although some side effects were worse (e.g., brain hemorrhage), the total number of adverse reactions was greater in the medication group. Whether stimulation of the subthalamic nucleus is neuroprotective, that is, prevents further degeneration, is presently under investigation. Thalamic stimulation is used for decreasing tremor. Therapists may find that intense treatment immediately after these surgeries may be able to take advantage of neural plasticity.

Fetal transplantation of the substantia nigra to the caudate nucleus remains under investigation. A double-blind, placebo-controlled trial was completed with mixed results. ^, Studies continue, including those of dose, cell type, and placement of cells. Recently, however, there was a report of Lewy-body inclusions in grafted cells 14 years after the transplant. The authors concluded that Parkinson disease was an ongoing process and that what caused the disease initially also affected the grafted cells.

Examination of the patient with Parkinson disease

Examination of an individual with Parkinson disease should assess impairments and functional activities and draw correlations of impact on participation in the individual’s life. Additionally, information regarding quality of life and the patient’s perception of their function and disease is extremely valuable. The use of objective outcome measures for the different International Classification of Functioning Disability and Health (ICF) domains is strongly recommended, with population specific cut-offs that correlate with function and predictors of future events (i.e., falls). It is essential to perform outcome measure testing at initial exam, with re-assessment at regular intervals to assess changes, modify interventions as appropriate, and allow for open, updated communication with patients, family, and physicians.

When assessing the overall clinical presentation of a person with Parkinson disease, the Hoehn and Yahr scale (see Table 18.1 ) is the most commonly and widely used to describe the severity of the disease. It is based on clinical features and functional disability, assigning a numerical value of dysfunction as it relates to unilateral or bilateral involvement, and whether postural stability is compromised. ^, Progression through the Hoehn and Yahr scale has prognostic implications—stage 3 has been correlated with increasing physical and cognitive impairment scores despite medication adjustments and therefore a marked deterioration in quality of life; however, it should be understood that this tool is not linear and does not include nonmotor functions. Because the scale provides an overall assessment of impairment and disability combined, clinicians should use it to create a general clinical picture of their patient and, as such, help guide their interventions and decision making.

The Movement Disorder Society Sponsored-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is the most widely used clinical rating scale for Parkinson disease. The scale assesses both nonmotor and motor symptoms associated with the disease, including nonmotor experiences, motor experiences of daily living, motor examination, and motor complications. ^{, , ,} The tool gathers information from the clinician’s exam, as well as from patient/caregiver response. It is sensitive in terms of detecting change in function and disability as the disease progresses (especially in the earlier stages of the disease), while having a high correlative value with the Hoehn and Yahr scale. ^, Another clinical scale is the Core Assessment Program for Surgical Interventional Therapies in Parkinson’s Disease (CAPSIT-PD), which includes timed tests for motor evaluation and neuropsychological testing. This scale was designed to provide minimal requirements and standardize assessments for those undergoing surgical intervention, and is used during the evaluation and consideration of a patient being considered for DBS surgery. Knowledge of these scales will help the therapist communicate with other health care professionals.

When completing an examination of a patient with Parkinson disease, subjective and quality of life questionnaires, in combination with functional activities assessment, will provide the most valuable information to guide treatment planning and goal setting. The Parkinson’s Disease Questionnaire (PDQ)-39 is a self-reported questionnaire that assesses how the disease impacts function and well-being. It is the most frequently used measure to assess health status in people with Parkinson disease and is recommended for all stages of the disease. The abbreviated PDQ-8 takes one item from each of the eight dimensions of the PDQ-39. Both the PDQ-39 and PDQ-8 are valid and reliable instruments to assess disease and health-related changes. Construct-specific subjective measures are also strongly recommended, including the Freezing of Gait questionnaire and Parkinson’s Fatigue Scale.

Five core areas should be assessed: physical capacity, transfers, manual activities, balance, and gait. In addition, a clinician should also assess respiratory function and pain. In the clinical setting, the exam should focus on impairments and functional activities. Highly recommended measures in the Body Structure and Function domain include MDS-UPDRS part 1 and the Montreal Cognitive Assessment (MOCA), while those in the Activity Limitation domain include 6-minute Walk Test, 10 m walk, mini-BESTest, Functional Gait Assessment (FGA), MDS-UPDRS part 2, five times sit-to-stand, and 9 Hole Peg Test. An integral component of the exam is a complete and thorough movement analysis during the tasks to generate links between impairments and activity limitation. Additionally, the time it takes to complete an activity must be measured. It is also valuable to address the effects of adding interfering stimuli (motor and cognitive) and complexity to a task to determine at which point a patient may begin having difficulties. ^,

Throughout all stages of the disease, a careful and comprehensive analysis of balance is imperative because a patient with Parkinson disease has a two to four times higher risk of hip fractures caused by falls compared to individuals without the disease. ^, The Activities-Specific Balance Confidence Scale (ABC) is highly recommended owing to its excellent reliability and validity in this population. ^, The ABC Scale, along with previous fall history and UPDRS motor score, were the most significant predictor of future falls. It has become more evident that balance impairments and increased fall risk are present even in the early stages of the disease; decreased confidence in self-perceived balance is a known contributor for future fall risk. ^, Assessing challenges to balance such as tandem walking or standing on a compliant surface is important because this may be the first sign of balance impairment. Posturography is the most sensitive measure of postural instability, especially in the early stages of the disease (Hoehn and Yahr stages 1 and 2). A clinically useful tool to assess dynamic balance is the functional reach test, which has been shown to be an effective, predictive tool in people with Parkinson disease as it is in the elderly, while the functional axial rotation (FAR) test has been shown to detect functional limitations in the early stages of the disease. ^, Evaluation of pain in an individual with Parkinson disease is important because this can have a detrimental effect on function and quality of life, although it is frequently underrecognized and often inadequately treated. While pain may come from different origins, pain of musculoskeletal origin is the most prevalent in people with Parkinson disease. ^, It is widely known that chronic pain can develop from, and lend itself to, avoidance of activities based on the fear of pain. This further exacerbates decreased participation in functional activities and, ultimately, progression of disease-related symptoms.

An assessment of chest expansion and vital capacity should also be included because of their contribution to the complication of pneumonia. For this reason, when rigidity is assessed, the muscles of respiration, extremity, and trunk movement should be included. Active and passive range of movement, general strength, chest expansion, and vital capacity should also be measured on regular intervals. Clinicians should also be aware of swallow function, sleep-disordered breathing, and cough mechanism because these can also contribute to respiratory limitations. Early recognition of contributors to respiratory limitations are imperative for timely interventions and, ultimately, improving quality of life and mortality. At present, a complete and easy-to-use form for evaluation does not exist for Parkinson disease.

General prognosis, treatment principles, and rationale

As with all treatment, the prognosis (functional goals, personal factors, and established time parameters) is based on the general goals related to the findings from the examination of each patient, the patient’s expectations, and functional requirements. Parkinson disease must be understood as a degenerative disease when establishing the prognosis and treatment plan, initially emphasizing a recovery model of care, then evolving to a maintenance/compensatory approach. In general, goals include increasing movement and range of motion (ROM) in the entire trunk and extremities, improving endurance, chest expansion with emphasis on posture, balance reactions, and restoring or maintaining functional abilities. Increased movement may in fact modify the progression of the disease. ^, Nonpharmacological and nonsurgical interventions, especially physical therapy treatment, are essential at the beginning of the disease owing to potential complications associated with chronic medication use and surgical procedures. Although levodopa decreases the bradykinesia, it alone will not be effective in increasing movement or improving balance; therefore aggressive intervention in the early stages is necessary.

Overall, physical rehabilitation is effective in the treatment of people with Parkinson disease and the results are greater when treatment is started early in the disease process. Although treatment initiated while the disease is still unilateral (Hoehn and Yahr stage 1) is more advantageous, it has been shown to be effective in Hoehn and Yahr stages 1 to 3. ^, The American Academy of Neurology recommends physical therapy in its practice parameters. Animal studies have shown that exercise can induce neuroprotective and neurorepair changes in the brain. Neuroprotective changes can slow the disease progression by increasing DA generation and availability, while neurorepair changes slow motor deterioration and disability by improving the efficiency of available DA. In the later stages of the disease, adaptive and compensatory approaches are utilized with increased reliance on undamaged systems, although increased angiogenesis and decreased brain damage marker expression in the striatum occur in response to exercise in animal studies. In the clinical setting, therapists tend to see patients after motor symptoms appear, and thus patients are already in the neurorepair or adaptation window of the disease.

Basic principles for treatment of the person with Parkinson disease will depend on the areas of impairment and functional limitations revealed in the evaluation. Certain principles, however, are true for all stages of the disease. Interventions should incorporate neuroplasticity parameters addressing intensity, repetition, specificity, difficulty, and complexity of practice. Interventions should integrate goal-based activities for skill acquisition while also requiring cognitive engagement, which is essential for learning to occur. Owing to diminished automatic movements from the loss of DA in the basal nuclei, increased cognitive control and attentional strategies are indicated. Asking the patient to generate goals and activities of their interest encourages patient investment and consistency, while a collaborative clinician-patient relationship helps improves compliance. Patients should engage in moderate to vigorous intensity-based training because higher-intensity training has been shown to induce DA D2 receptor-binding potential; this pathway has been implicated in increasing inhibitory drive, leading to motor impairments caused by decreased DA. Interventions should also address balance and an emphasis on increasing amplitude of movement because the DA-depleted state results in slower and smaller movements. Treatment should also involve strengthening, gait training, incorporating transitional movements (changes in directions and turns), and dual-tasking activities.

Variety is important to facilitate shifts in movement as well as in thought. To date, many rehabilitative techniques and exercises have demonstrated improvement in function for people with Parkinson disease, and numerous randomized clinical trials have proven the efficacy of the varied techniques. Programs that emphasize sensory-motor integration, agility, and motor learning demonstrate decreased progression of disease and improved motor function. Programs that involve dual motor-cognitive tasks, complex sequences of movements, and force the participant to quickly change movements dependent on environmental conditions have resulted in improved performance on the Timed Up-and-Go Test, the UPDRS, the 10 m walk test, and a variety of balance tests. The words big, fun, and novel are good words to remember when planning treatment.

Although a majority of evidence supports interventions in the earlier stages of the disease (Hoehn and Yahr stages 1 to 3) and there is evidence of some disease modification in the later stages, as the disease progresses, goals may shift to more task-specific activities, assessment and training for assistive devices, addressing posture and positioning for respiratory and pain management, and caregiver training. Task-specific activities often include turning in bed, getting in/out of bed, rising from a chair, dressing, grooming and hygiene activities, and being aware of posture. At the later stages of the disease, breathing exercises and positioning will need to be a more prominent aspect of treatment. Throughout the course of the disease, large amplitude movements during all activities should be emphasized. Frequent conversations with the patient and caregivers regarding expectations, concerns, and caregiver training should also be ongoing throughout the provider’s care.

Therapeutic programs and approaches.

As previously stated, exercise itself is important for the person with Parkinson disease. There is a relationship between longevity and physical activity, with those who exercise having lower mortality rates. A link has been demonstrated between a lack of exercise and development of Parkinsonian symptoms. Some evidence also indicates that exercise may alter the magnitude of free radicals and other compounds linked to aging and Parkinsonism. Given the evidence that physical activity can induce disease-modifying changes, especially in the earlier stages of the disease, it is strongly recommended to establish a consistent exercise routine as early as possible in the disease process. ^,

Individuals with Parkinson disease are strongly encouraged to achieve the World Health Organization’s recommendations for physical activity. Intensity has been shown to be necessary for beneficial effects, so patients are encouraged to perform 3 days of moderate intensity activity and 2 days of vigorous intensity exercise per week, as well as at least 3 days of balance training and 2 days of muscle-strengthening exercises. For individuals who may be at a lower activity level, shorter bouts of exercise of at least 10 minutes should be encouraged to reach the recommended dosage. Clinicians are encouraged to gradually increase intensity when first introducing higher effort exercises with use of percentage of maximum heart rate and/or perceived exertion. ^,

Movement throughout a full ROM is crucial, especially early in the disease process, to prevent changes in the properties of muscle itself. Rigidity of some degree is present in up to 99% of people with Parkinson disease, with the contractile elements of flexors becoming shortened and extensors becoming lengthened, enhancing the development of the flexed posture that is traditionally present. Rigidity can be the cause of, and further contribute to, the pain the patient may experience. For most patients, treatment proceeds better if rigidity is decreased early in the treatment session. Many relaxation techniques appear to be effective in reducing rigidity, including gentle, slow rocking, rotation of the extremities and trunk, and the use of yoga. Yoga is also beneficial to target spinal extensor strength and flexibility. Furthermore, because the proximal muscles are often more involved than the distal muscles, relaxation may be easier to achieve by following a distal-to-proximal progression. The inverted position may be used with care. Initially, this position facilitates some relaxation (increase in parasympathetic tone) and then increases trunk extension, which is important for the Parkinsonian patient. Once a decrease in rigidity has been achieved, movement must be initiated to use the newfound range in a functional way.

Implementation of aerobic exercise is essential in the management of a patient with Parkinson disease. The role of aerobic fitness itself may be a factor in reducing dysfunction, with studies showing that it may be necessary to promote neuroplasticity to help restore automatic movement. Animal studies indicate that functional exercise decreased DA loss after a variety of lesion models. ^{, ,} As stated before, clinicians should emphasize increased intensity into their interventions to gain the aforementioned benefits. Animal research indicates that exercise and forced functional movements may protect the dopaminergic neurons, with earlier intervention having greater beneficial effects on the dopaminergic system. ^, Alberts and colleagues performed a classic study investigating the use of tandem bicycling, during which a person with Parkinson disease was required to pedal at a higher rate and intensity than their preferred rate. They found this forced exercise led to increased connectivity between cortico-subcortical regions that underlie automaticity on fMRI, and the pattern of activation was similar in patients who were on medication and those following forced exercise while off medication. Furthermore, a study investigating the effects of high-intensity, moderate-intensity, and a no exercise control group demonstrated that the high-intensity exercise group had significantly lower reductions in mobility scores at 6 months follow-up compared to the control group, while the moderate group did not experience a significant change. High-intensity interval training is often utilized to help patients achieve the intensity and time necessary for neuroplastic changes to occur.

Aerobic exercise may also improve pulmonary function in patients with Parkinson disease because these functions appear to suffer from deficiencies in rapid force generation of the respiratory muscles, similar to limb musculature. If patients practice regular physical exercise in conjunction with disease-specific exercises, the ill effects of inactivity will not potentiate the effects of the disease process itself. Although most patients with Parkinson disease can achieve an adequate exercise level, many patients have low fitness levels before the medical diagnosis. Exercise, even once a week, can be effective in improving gait and balance in patients with Parkinson disease when practiced over several months. ^, Given these benefits, as well as known benefits of general aerobic exercise on brain and cardiopulmonary health, it is concluded that regular aerobic exercise is the single strategy with compelling evidence for slowing Parkinson disease progression. Programs emphasizing sensory awareness of the size of movement have shown improvement in both speed of limb movement and gait parameters. ^{, ,} In Parkinson disease, for any given amplitude of movement, velocity of movement is reduced, with velocity decreasing as the amplitude of movement gets larger. Cues for large amplitude movements result in bigger and faster movements as opposed to cues for speed. There are various programs that employ sensory awareness for amplitude of movement, such as PD SAFEx, LSVT BIG, and Parkinson’s Wellness Recovery (PWR!). Sensory awareness programs have evolved to incorporate movements that specifically address the primary Parkinson disease movement deficits while integrating balance, coordination, and automaticity. Furthermore, patients are encouraged to perform these movements in different postures to challenge the body in functional positions. These programs have been shown to improve gait and function on the UPDRS. These authors concluded that programs emphasizing increased sensory feedback and awareness, with emphasis on amplitude and effort, are the best behavioral strategy to decrease hypokinesia and bradykinesia while improving the function of people with Parkinson disease.

Treadmill training has been used in Parkinson disease exercise programs, with strong recommendations of its use to improve walking speed and stride length, improve balance, reduce fear of fall, and number of falls. ^{, ,} In addition to forward walking, multidirectional treadmill training (backward, left, and right sidestepping) at the patient’s fastest tolerated speed in each direction improved spatiotemporal gait measures in all walking directions, balance performance, and gait kinematics. The use of the treadmill with body-weight support increases safety and allows the therapist to control speed of movement, introduce perturbations, and challenge multidirectional walking. Studies have shown that cued treadmill training, such as visual cues to target stride length or auditory cues for gait speed, exhibits good results and carryover to the home. Cognitive tasks and other dual tasks have also been added during treadmill training with good results.

Rhythmical exercise has been shown to decrease rigidity and bradykinesia and improve gait over time. ^{, ,} Ballroom dancing is a form of rhythmical therapy for patients with Parkinson disease that incorporates rotation, large amplitude and multidirectional movements, weight shifting and turning, speed variation, and coordination. ^, Given that dance requires high-level multitasking and progressive learning, it is both cognitively and physically challenging; the socialization aspect can help improve mood and adherence. While tango has been the mostly widely researched form of dance, other forms have also shown to have benefit. A program of tango versus waltz and foxtrot indicated that both groups improved on the UPDRS motor scale, Berg Balance Scale, 6 minute walk distance, and backward stride length, although the tango group had greater improvements. ^{, ,} The waltz and foxtrot, which are easier dances, may be beneficial for those at more advanced stages of the disease. Latin dance and other weight-bearing exercises demonstrated similar improvements in balance and especially initiation of gait. ^{, , ,} Dance therapy also has beneficial effects on cognitive tasks, with improvements seen on the Brooks Spatial Test and Trail-Making Parts A and B. Similar effects were seen in tai chi as a form of rhythmical therapy, which demands attention to movement and increases challenges to balance and control of movement. Tai chi has been shown to be effective in improving gait and balance parameters, as well as nonmotor function such as mood and overall quality of life. ^, There is growing evidence for the use of technologies in Parkinson disease rehabilitation. Virtual and augmented reality can be used to optimize motor learning in a safe environment, stimulating motor and cognitive processes while providing augmented feedback about performance and address repetition and task specificity. Although there is currently limited high-quality evidence, virtual reality interventions have greater effects on step and stride length compared to conventional therapy, and similar gains in balance, ADL function, Quality of Life (QOL), and cognitive function compared to conventional therapy. Mirelman and colleagues demonstrated that an intensive treadmill program incorporating virtual reality obstacle negotiation significantly improved fall risk and fall rates 6 months after training compared to treadmill training without virtual reality. For some with Parkinson disease, even in the early stages, games are too fast or too confusing; therefore the use of disease-specific exercise programs may be superior to commercial systems and could be used and enjoyed by those with Parkinson disease. There is also growing research into biofeedback, in which a somatosensory cue is provided in real time to improve balance and weight shifting to minimize freezing of gait. Despite the limited research and evidence, technological advances and its use in rehabilitation for Parkinson disease is promising.

Physical activity and movement can increase quality of life by decreasing depression and improving mood and initiative. ^, Group classes can serve as an extra support system for patients with Parkinson disease and their spouses, providing both extrinsic and intrinsic motivation. Exercise programs should be designed to meet, and progress, a patient’s current functional level. A carefully structured low-impact aerobics program appears to be beneficial to patients even with long-standing disease. For example, individuals in Hoehn and Yahr stage 2.5 or 3 can begin with seated activities with upper-extremity exercises ( Fig. 18.8 A) and combination movements (see Fig. 18.8 B) then progress to standing and marching activities that incorporate coordinated movements of arms and legs, balance, and trunk rotation ( Fig. 18.9 ). All movements are performed to music similar to that used in aerobics classes in any gym or health club ( Fig. 18.10 ). A cool-down period allows participants to practice fine motor coordination activities of the hands ( Fig. 18.11 ). Many Parkinson disease associations also have audiotapes for exercises (e.g., United Parkinson Foundation).

Seated Aerobics or Warmup Exercises.

(A) Patients are using bilateral upper-extremity patterns to facilitate trunk rotation. Instruction was to let the head follow the hands. (B) This exercise encourages trunk rotation, large movements, and coordination of the upper and lower extremities. Patients are to reach with the arms and touch the opposite foot. This coordination is difficult for those with Parkinson disease, and many patients initially could not move their arms and legs at the same time.

Initial Warmup in Standing.

Patients are to walk with their head up, with the back as straight as possible, and to take large steps. When the group began, walking was the major aerobic activity and was used to increase endurance and encourage movement. Nonambulatory patients march in place while seated.

Walking in a “Waltz Rhythm” (Slow, Quick, Quick) Emphasizes a Big Step for the Slow Step.

Note lack of automatic arm swing. Also, note flexed posture of seated patient during rest period.

Cool-Down Period Allows Time to Work on Fine Finger Movements.

Thumb abduction with rounded fingers and various rhythms are used to increase coordination. Note “masked face” appearance.

Most studies have found that exercise under the guidance of a physical or occupational therapist or trained instructor is effective in reducing Parkinsonian symptoms. ^{, , ,} There is long-standing evidence of the benefits of exercise, with improvements in gross and fine motor functions, as well as of general well-being ; however, it is necessary for continued, consistent participation for long-term carryover. The most successful exercise programs appear to be those that incorporate context-dependent responses and a varied environment ( Box 18.1 ), although noncontext-dependent aerobic exercises are also effective ( Box 18.2 ). Research has shown the importance of adjusting the response to the specific task and has also demonstrated the importance of practice for the Parkinsonian patient. ^, The principles of motor learning are of paramount importance in the treatment program of these patients. Random practice may enable the patient to learn the correct schema by which to regulate the extent, speed, and direction of the movement and may also be important in facilitating the ability of the patient to shift attention and to learn to access “working memory.” The Parkinsonian patient may benefit from visual instruction and mental rehearsal before performing the movement. ^, In addition, the instructions used need to be pertinent to the task at hand.

BOX 18.1

Hackney ME, Lee HL, Battisto J, et al. Context-dependent neural activation: internally and externally guided rhythmic lower limb movement in individuals with and without neurodegenerative disease. Front Neurol . 2015;6:251.

Exercises That Promote Context-Dependent Responses

The following exercises promote context-dependent responses and are recommended for people with movement disorders:

• 1.
  

  Walking outdoors

  
  
• 2.
  

  Karate and other martial arts (Tai Chi and Qi-Gong specifically)

  
  
• 3.
  

  Dancing (all forms), particularly to music

  
  
• 4.
  

  Ball sports (various types)

  
  
• 5.
  

  Cross-country and downhill skiing

  
  
• 6.
  

  Well-structured, low-impact aerobics classes

  
  
• 7.
  

  Treadmill training with guidance of a movement specialist

This list is a sample of activities; it should not be considered all inclusive.

BOX 18.2

Exercises That Promote Fitness and Increase Range of Motion But Not Context-Dependent Responses

The following exercises promote fitness and increase range of motion but not context-dependent responses and are recommended for people with movement disorders.

• 1.
  

  Treadmill walking without guidance or supervision

  
  
• 2.
  

  Stationary bicycle riding

  
  
• 3.
  

  Using strengthening machines and free weights (with low weights or low resistance)

  
  
• 4.
  

  Using step exercises and stair climbers

  
  
• 5.
  

  Using rowing machines

  
  
• 6.
  

  Swimming laps

This list is a sample of activities; it should not be considered all inclusive.

Differences between Parkinson disease and atypical Parkinsonisms: Theoretical and practical considerations

Several other neurodegenerative diseases are grouped together as “atypical Parkinsonisms” disorders. Patients with these syndromes usually have limited to no response to levodopa intervention and tend to progress more rapidly than Parkinson disease. The most common of these is progressive supranuclear palsy (PSP). Clinical features include progressive onset of symmetric symptoms, lack of tremor, bradykinesia, increased rigidity in the trunk and legs, frequent falls early in the disease, and pseudobulbar features (dysphagia, dysarthria, and emotional lability). They also present with vertical gaze palsy. These patients can be evaluated and treated in a manner similar to patients with Parkinson disease. Treatment is aimed at symptom management and relief, although within a decade the patient is typically immobile.

Multiple system atrophy (MSA) is the second most common atypical Parkinsonism that affects various areas of the CNS, with varying degrees of pyramidal, cerebellar, and autonomic dysfunction. The disease is characterized by symptoms including rigidity, bradykinesia, postural instability, ataxia, bladder dysfunction, and orthostatic hypotension. There are two main phenotypes: MSA-P, which presents with Parkinsonism-dominant features, or MSA-C, which presents with predominantly cerebellar features. Almost all patients will develop autonomic dysfunction, while those with MSA-P are more likely to have a greater functional decline. Cognitive impairments occur in some patients, including decreased executive function, loss of verbal memory, verbal fluency, and difficulty maintaining attention. Assessment and treatment should be focused on addressing impairments and symptom management while maintaining/improving mobility.

The least common atypical Parkinsonism is corticobasal syndrome. As the name suggests, it involves cerebrocortical and basal nuclei dysfunction, characterized by asymmetric motor impairments, apraxia, myoclonus, postural tremor, speech and swallowing impairments, and predominantly upper limb dystonia. Cognitive deficits are not a predominant feature. In some cases, patients may experience “alien limb phenomenon.” Interventions should be focused on symptom management.

Dementia with Lewy bodies is a progressive, neurodegenerative disease that shares symptoms of both Parkinson disease and Alzheimer disease caused by abnormal deposits of alpha-synuclein protein in multiple areas of the brain. One of the characteristic features is the appearance of cognitive impairments before motor symptoms. Progressive cognitive decline, confusion, changes in attention, and hallucinations or delusions are often seen. While the Parkinsonian features may be responsive to Parkinson disease medications, cognitive involvement may make rehabilitation and carryover difficulty, and treatment should be focused on symptom management.

Because these syndromes are rarer than Parkinson disease and far more variable, there are limited studies that have been undertaken regarding rehabilitation intervention efficacy. Accurate differential diagnosis is important in patient planning; thus a thorough evaluation by a neurologist is highly recommended.

Symptoms

Huntington disease is characterized by a triad of signs and symptoms involving movement, cognitive, and psychiatric disorders. Some of the signs and symptoms of Huntington disease are similar to those of Parkinson disease: abnormalities in postural reactions, trunk rotation, distribution of tone, extraneous movements, as well as a decrease in associated movements (e.g., arm swing). Individuals with Huntington disease, however, are at the other end of the spectrum; rather than a paucity of movement, they exhibit too much movement, which is evident in the extremities, trunk, and face. The extraneous movements are of the choreoathetoid type–involuntary, irregular isolated movements that may be jerky and arrhythmical as in chorea, to rhythmical and worm-like as in athetosis. The gait takes on an ataxic, dancing appearance (in fact, chorea means to dance in Greek), and fine movements become clumsy and slowed. ^, Usually, however, these movements occur in succession so that the entire picture is one of complex movement patterns. The “movement generator” aspects of the basal nuclei seem to be continuously active, as would fit the hypothesis of a disruption in the indirect pathway; however, as the disease progresses, the choreiform movements may give way to akinesia and rigidity. This is caused by the excitatory direct pathway of the basal nuclei becoming affected in the later stages of the disease, which inhibits thalamic activity and results in decreased activation of the cortex.

Disruptions in voluntary movement for the person with Huntington disease further reflect the role of the basal nuclei in movement. The person with Huntington disease, like the person with Parkinson disease, has difficulty responding to internal cues, as well as internal rhythms. Kinematic analysis of upper-extremity complex tasks demonstrates that the person with Huntington disease must rely on visual guidance in the termination of a movement. This has been interpreted to indicate impairment in the development and fine-tuning of an internal representation of the task. Furthermore, these patients have increasing difficulty with more complex movements in the absence of advanced cues. ^, The lack of internal cuing in the person with Huntington disease has been linked to the increased variability of response seen in these patients.

Gait patterns of the person with Huntington disease are in some ways similar to those of Parkinson disease. Gait velocity and stride length are decreased, with the decrease in velocity correlating with disease progression. Unlike the person with Parkinson disease, however, the person with Huntington disease has a decreased cadence as well. The base of support is increased (again unlike the pattern seen in Parkinson disease). In addition, lateral sway is increased along with great variability in distal movements. Balance impairments are manifested as increased sway in static and dynamic standing, with delayed balance recovery reactions. A combination of disease severity, lower limb weakness, cognitive impairment, and executive dysfunction have been found to influence balance and mobility in people with Huntington disease. The face is also affected in Huntington disease. Impaired voluntary eye movement is often the first sign of Huntington disease, with noted difficulty with initiation and control of saccadic eye movements and smooth pursuits. Speech, breathing, and swallowing lack normal control and coordination. Speech lacks rhythm, variability in volume control, and mistiming in breath control, as might be expected with decreased internal timing. Timing and coordination of the swallowing mechanism is also impaired and can lead to choking, aspiration, and weight loss. Studies suggest that a person with decreased body weight and a parental history of the disease is at greater risk of disease development and progression. ^{, ,}

The exact mechanisms for the production of choreoathetoid movements are unknown. Because these extraneous movements are part of a person’s normal repertoire of movement patterns, they may be “released” at inappropriate times and without any modulation. A postmortem examination showed a decrease in GABA that was greater in the globus pallidus external segment than the internal segment, while the recent use of positron emission tomography (PET) scans demonstrates loss of ACh and GABA neurons. A pattern may therefore be executed before it is necessary, and inappropriate portions of a movement pattern cannot be inhibited. Petajan found motor unit activity indicative of bradykinesia. Recordings of single motor units in the muscles indicates that persons with Huntington disease have a loss of control evidenced by an inability to recruit single motor units. As the efforts at control increased, these individuals demonstrated an overflow of motor unit activity that resulted in full choreiform movements. Those in the earlier stages of the disease demonstrated what the experimenters termed “microchorea,” or small ballistic activations of motor units. As in Parkinson disease, difficulty occurs in modulating motor neuron excitability. Yanagisawa used surface Electromyography (EMG) recordings to classify involuntary muscle contractions in Huntington disease patients with varying movement disorders from chorea to rigidity. He found brief, reciprocal, irregular contractions in those patients with classic chorea, and tonic nonreciprocal contractions in those patients with rigidity. Presence of athetosis or dystonia was associated with slow, reciprocal contractions. During sustained contractions, EMG activity demonstrated brief, irregular cessation of activity in the choreic patients; thus patients with Huntington disease have interruption of normal motor function at rest and during sustained activity (e.g., stabilizing contractions).

In addition to the involvement of the motor systems, the individual with Huntington disease also shows signs of cognitive and behavioral disorders that become worse as the disease progresses. Cognitive impairments include difficulties in planning, memory impairments, poor initiation, impulsivity, lack of insight, perseveration, and severe deterioration in the ability to communicate (e.g., speech and writing). Psychiatric changes include depression, hostility, irritability, paranoia, apathy, and anxiety. Ideomotor apraxia and apraxia of speech can also occur, especially as the disease progresses. Intellect decreases, with performance measures decreasing more rapidly than verbal levels. Neuropsychological tests are therefore part of the Unified Huntington’s Disease Rating Scale (UHDRS).

Stages of Huntington disease

Huntington disease is a progressive disorder. The initial motor symptoms are most often incoordination, clumsiness, or jerkiness. A classic test for eliciting choreiform movements in this early stage is a simple grip test. People with Huntington disease displays what is descriptively called the “milkmaid’s sign”; alternating increases and decreases in the grip that are perhaps the equivalent of the electromyographic abnormalities seen during sustained contractions. Facial grimacing or the inability to perform complex facial movements also may be present very early. As mentioned, the patient with Huntington disease will initially exhibit hyperkinetic movements with deficits in gross and fine motor control, eventually progressing to a hypokinetic presentation and significant debility in the late stage.

In most cases the cognitive and psychological impairments of Huntington disease occur before the onset of the motor signs; cognitive impairments have been reported at least 15 years prior to when a motor diagnosis is given. As the disease progresses, cognition will progress from difficulty with complex tasks to intellectual decline with impaired insight and dual tasking, ultimately progressing to global dementia in the late stages. In cases in which very subtle personality changes occur first, the diagnosis may be more difficult. Such persons may appear depressed, irritable, or forgetful, but can then develop apathy, perseveration, antisocial behavior, and experience delusions or hallucinations; the late stage is characterized by delirium. Early diagnosis may be important, and SPECT shows promise for early detection of the disease.

With time, the combination of the motor, cognitive, and psychiatric problems cause the individual to lose all ability to work and perform ADLs. Eventually, this person can only be cared for in an extended care facility. By this time, the choreiform movements have given way to rigidity, and the patient is bedridden. Death is usually caused by infection, but suicide is also common. Fig. 18.12 shows the stages of Huntington disease according to Shoulson and Fahn. ^,

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Contemporary issues and theories of motor control, motor learning, and neuroplasticity Medical and developmental challenges of infants in neonatal intensive care: Management and follow-up considerations Neuromuscular diseases Brain tumors Aging, dementia, and disorders of cognition Electrophysiological testing and electrical stimulation in neurological rehabilitation

Stay updated, free articles. Join our Telegram channel

Join