Implications of pathology for understanding the movement disorder

The striatum receives excitatory inputs from the cortex. The efferent medium spiny neurons contain inhibitory neurotransmitters which project to the internal globus pallidus via direct and indirect pathways (Albin et al., 1989). Figure 7.3 shows a simplified diagram of the process. In broad terms, damage to the indirect pathway leads to overstimulation of the thalamo-cortical feedback and chorea (random purposeless movements), whereas loss of the direct pathway results in increased inhibition of the thalamus and less activity of the thalamo-cortical feedback producing bradykinesia and rigidity. Although both pathways degenerate, the balance between them is disturbed. The medium spiny neurons of both the direct and indirect pathways contain dopamine receptors, which are consistently reduced in Huntington’s disease. Conventionally, excitatory D1 receptors are on the direct and inhibitory D2 receptors are on the indirect pathway. This means that whilst it is possible to control the chorea of patients with dopa blocker and dopa depleting drugs, this may worsen the bradykinesia and dystonia.

Figure 7.3 Connections of the basal ganglia, showing the pathways damaged in Huntington’s disease. GABA, gama-aminobutyric acid.

Implications of pathology for understanding the behavioural problems

Of equal importance to the understanding of the condition is that there are fronto-striatal connections which are disturbed. At first this may result in a patient becoming less perceptive of the needs of others, which may be noticed by close family members. As time progresses they become less able to switch between tasks, plan ahead or change a plan in the light of new information and become increasingly self-centred. This results in patients becoming irritable and having temper outbursts much more easily. In addition, there may be problems with anxiety and depression. Family members become adept in working around these behavioural changes by minimizing provocations and allowing outbursts to blow over. As part of the fronto-striatal changes, a patient may lose interest in activities and become apathetic.

As an example, a patient with HD may decide it is time to be taken for a walk. A professional may reasonably explain that they are busy working with someone else and they will take the patient for a walk presently. This may pacify the HD patient temporarily only for that person to return a few minutes later requesting that they be taken for a walk. Knowledge of the cognitive and behavioural problems of HD may enable a professional to understand the need to explain what is going to happen to the patient and perhaps repeat the explanations.

At present, there is no treatment to delay the onset of HD or to slow down the rate of neurodegeneration. However, much can be done to educate families and professionals to work around the behavioural problems; pharmacological interventions such as antidepressants and dopa blockers should be used to manage the behavioural aspects of the condition.

Understanding pathology at the level of the cell

HD should be easy to explain because one gene is involved with one mutation that affects a single protein. Unfortunately, this is not the case because huntingtin is involved in many cellular processes. Apart from man, no natural animal develops HD. Following the identification of the gene a tremendous research effort involved developing animal models. The first of these, and most studied, was the R6 mice which contain multiple copies of the first part of the HD gene (Mangiarini et al., 1996). These mice die before they develop significant cell death. One feature of the cells is that they contain aggregates of the first part of the huntintin protein (Davies, et al., 1997). These aggregates are now recognized as occurring in human HD brains (DiFiglia et al., 1997). It is unclear as to whether these aggregates are directly related to the cellular pathology or represent a defence mechanism within the cell. There are a number of different animal models; details of their similarities and differences are not relevant to this chapter, but animal models have enabled an understanding that neuronal cells are dysfunctional (‘sick’) before they die which gives hope for interventions to alter the natural history of the disease. This natural history is modelled in Figure 7.4 with neuronal dysfunction preceding the onset of symptoms. In the absence of serendipity, an understanding of the pathology at the cellular level using animal and cellular models is the way forward for developing and subsequently testing new treatments for HD.

Figure 7.4 Primary physiotherapy aims and the continuum of Huntington’s disease.

(Modified from the Walker et al., Huntington’s Disease. Lancet 2007;369 (9557): 218-28, with permission from Elsevier.)

Life history of the disease

If a person has inherited the gene there will be a period of time where she/he is completely asymptomatic. In time, the neurones become dysfunctional. Onset of HD is insidious with non-specific problems such as mood change or being slightly forgetful, which can be attributed easily to other mundane causes. A person in this prodromal stage may become depressed, but a clinical diagnosis cannot be made confidently until motor signs, such as chorea, appear. These may be infrequent, of low amplitude and may not be noticed by the patient, family or clinician with limited experience of the condition. Indeed even at a time when the chorea is quite obvious it may be denied as a problem by the patient (Snowden et al., 1998).

If a patient is seen when there are obvious signs of HD, the CAG repeat size may be measured from a venous blood sample to confirm the clinical diagnosis. It is important to realize that the result of the genetic test will be the same whether the individual is completely asymptomatic, in the prodromal phase, or in the early, middle or later stages of HD. As with any test the interpretationof the test result depends upon the clinical context. This raises an important issue about the genetic test: it is a ‘trait marker’ but says nothing about the state of the illness. There is a significant research effort to determine other laboratory biomarkers (‘state markers’) which can track the development and progression of the disease (Henley et al., 2005). The boundaries between early, middle and late stages are ill defined, but nonetheless they form a useful way of categorizing the impact of HD.

Stage I (Early stage)

In the early stages of the disease, the person with HD is able to remain functional and independent, retaining their ability to work and drive (HDSA, 2000). Movement disorders include minor involuntary movements, reduced coordination and linearly progressive motor impersistence or inability to maintain a voluntary muscle contraction at a constant level (Walker, 2007). Even at this stage, it may be possible to detect some slowing of saccadic eye movements (rapidly moving the eye to a new target; this is done by asking the patient to move his/her eye to one corner in response to a cue). Voluntary motor tasks (fine and gross motor skills) may become increasingly difficult as the disease progresses (Aubeeluck & Wilson, 2008). Cognitive tasks also become more difficult with reduced ability to sequence and organize information (HDSA, 2000). Deficits in gait have been identified across the spectrum of HD (Churchyard et al., 2001; Grimbergen et al., 2008; Hausdorff et al., 1998; Koller & Trimble, 1985; Rao et al., 2008). Decreased gait velocity, stride length, and increased time in double support compared to healthy controls may occur (Rao et al., 2008). These impairments appear to worsen with increasing disease severity and can be useful markers of disease progression and treatment efficacy.

Stage II and III (Middle stage)

During the middle stages of HD, involuntary movements such as chorea increase. In the early stages of HD, this is typically seen in the fingers, hands and face muscles, but as the disease progresses, it can be seen throughout thebody, including in all four extremities and the trunk. Chorea does not usually result in a direct impairment of motor function, however voluntary motor impairments may have a functional impact (Walker, 2007).

Dystonic postures (abnormal, sustained posturing) in sitting or standing (Louis et al., 1999) and in movements such as shoulder elevation, foot inversion and supination, and trunk extension might be present. People may experience frequent loss of balance and falls, which interfere with their ability to walk and maintain an upright position (Busse et al., 2009). Common tasks during which patients demonstrate balance problems include those where the base of support is decreased; tandem standing and walking, dual tasks, eyes closed and in response to external perturbations (Bilney et al., 2003b; Quinn & Rao, 2002). Falls are frequent in people with HD; 60% of people with early to mid-stage HD in two separate studies (n=45 & n=24) reported two or more falls in the previous 12 months (Busse et al., 2009; Grimbergen et al., 2008). Falls can have physical and psychological consequences (Myers et al., 1996). The fear of future falls may be a more pervasive problem than falls per se, as fear of falls may lead to people restricting their physical activities. Self-imposed restriction of daily activities leads to immobility and consequently osteoporosis, reduced fitness and social isolation (Grimbergen et al., 2004). Individuals with HD have also been found to have lower-limb muscular weakness compared to age-matched controls (Busse et al., 2008a). Strength can be measured clinically by manual muscle testing or by functional observation of strength during task performance (e.g. stair climbing or evidence of gait deviation during walking).

Stage IV and V (Late stage)

In the advanced stages of the disease motor symptoms continue to progress, severely limiting mobility. Choreic and dystonic movement may further increase (see Figure 7.4), but involuntary movements are often overshadowed by Parkinsonian symptoms (Aubeeluck & Wilson, 2008; HDSA, 2000) such as bradykinesia or slowness of movement. People with HD can also experience pain, particularly in the later stage of the disease. The source of this pain can be unknown; however, dystonia or muscle imbalances can often cause musculoskeletal pain. Excessive chorea can cause pain if people injure themselves by hitting their arm or leg into an object or hard surface.

Weight loss can occur in part due to impaired swallowing function (Aubeeluck & Wilson, 2008; HDSA, 2000). People may no longer be able to work or drive and will need assistance when performing some activities of daily living (ADL) (HDSA, 2000).

Even though people with HD appear to be in constant movement, their underlying volitional movements during task performance have been found to be slower than healthy controls for reaching (Quinn et al., 2001) and ambulation (Delval et al., 2006; Delval et al., 2007). Bradykinesia can typically be evaluated by measuring time to complete a task (movement time). Akinesia or delayed initiation of movement is also seen. In research studies, akinesia is typically measured by reaction time. In the clinical setting, it is often difficult to quantitatively evaluate akinesia, but delays in onset of movement for various tasks can be noted. Impaired speech results in difficulties communicating, and cognitive and psychiatric deterioration may continue, but it is thought that patients retain some comprehension (HDSA, 2000). At this stage most people will require assistance in all aspects of daily living, relying fully on nursing care (HDSA, 2000). Despite the severity of the neurological disorder, the primary causes of death in HD are aspiration pneumonia, cardiovascular disease and complications from falls (Sorensen & Fenger, 1992; Walker, 2007).

Physiotherapy assessment

The physiotherapy aims should be both anticipatory and responsive to the disease stage (see Figure 7.4) with interventions to assist HD patients to maintain independence, functional capacity and participation in society (Bilney et al., 2003a).

The World Health Organization International Classification of Functioning, Disability and Health (ICF) (WHO, 2001) is useful as an aid in structuring assessment of a person’s functioning and participation (see Figure 7.5), and in allowing consideration of the triad of motor, cognitive and psychiatric symptoms that are often seen in HD. The ICF can be used for functional status assessment, goal setting and treatment planning, and focuses on aspects of a person’s health and health-related wellbeing in terms of activities and participation, i.e. the description of the tasks (activities) and/or life situations (participation) in which the person wishes to engage, and the impact that impaired body function or structure is having on these aspects. The ICF further takes into consideration the contextual factors (both environmental and personal), which may impact on a person’s life, and the relationships with body function/structure, activities and participation. The specific impairments and associated activities and participations that may need consideration when assessing a person with HD are listed in Table 7.2. Documentation of the impact of the noted impairments on functional abilities, activities and participation is important to help highlight specific factors that contribute to a patient’s functional problems and inform the clinical reasoning process in terms of maximizing functional abilities. Qualifiers of the degree of impairment, and the performance and capacity of activities and participation enable essential documentation of disability and health status.

Figure 7.5 Illustration of the WHO ICF domains and coding to the Huntington’s disease triad. Bold text indicates areas that are key components of the physiotherapy assessment.

Table 7.2 Specific impairments and associated activities and participations that may need consideration when assessing a person with Huntington’s disease

Specific coding for the domains are shown.

The subjective assessment allows the physiotherapist to evaluate the patient’s presenting problem(s), in the contextof their past medical history and how this may affect their ability to live independently and within society. This also provides the opportunity to build a therapeutic, collaborative relationship, and facilitate realistic goal setting. It must be noted that the patient’s caregiver(s) should be involved, particularly if the patient has difficulties communicating as a result of cognitive or physical impairment. The objective assessment should include assessment of neuromuscular, musculoskeletal (posture, range of motion, pain and muscle strength), cardio-respiratory and cardio-vascular impairments. An overview of the HD specific considerations for the physiotherapy assessment is shown in Table 7.3. These are useful to aid clinical reasoning and goal setting but are not necessarily outcomes that are sensitive to change over time. There are numerous outcome measures that have potential utility in the assessment of efficacy of physiotherapy interventions for people with HD. Measurement tools that have been used in previous HD-related studies are presented in Table 7.4 and are classified according to the WHO ICF. The Berg Balance Scale, Timed Up and Go Test and the Functional Reach Test have all been found to be valid and responsive clinical measures in HD and are considered useful to detect those at risk of falls (Busse et al., 2009; Grimbergen et al., 2008; Rao et al., 2009).

Table 7.3 Specific assessment points for consideration in Huntington’s disease

Table 7.4 Classification of outcome measures according to the WHO ICF

Early and middle stage management

The primary goal of patients with HD in the earlier stages of the disease who are undergoing physiotherapy is often to improve their walking ability (speed, coordination, balance) or to simply continue walking for as long as possible.

The focus of gait training should be on identifying those aspects of gait which are functionally limiting (Rao et al., 2008), and then designing an intervention plan that is aimed at ameliorating or compensating for the gait impairments, and providing training so that the patient can reach their ambulation goals. The influence of the practice environment on learning and carryover, and interaction with the environment directly affects the movement that emerges (Bassile & Bock, 1995). Structuring practice of walking within an environment that is realistic to the current life situation of the person with HD is likely to yield the best results.

Balance training and strengthening of the postural muscles (core stability) should begin in the early stage of the disease and should take place in the environment where the individual’s problems are most apparent. General flexibility and strengthening programmes may also be required in line with impairments documented.

Balance activities should be task specific (Shumway-Cook & Woollacott, 2001). Progression from a wide to narrower base of support, from static to dynamic activities, from a low to high centre of gravity, and increasing the degrees of freedom that must be controlled can be considered; however, the key principle is that the balance demand of a specific task should be assessed and addressed. Task-specific training is particularly appropriate for people with movement disorders (Bilney et al., 2003a, 2003b) because motor disturbances are typically context-dependent, and are typically seen in complex, well-learned tasks such as walking and reaching. People should be taught to deliberately prepare in advance for forthcoming threats to balance, or to focus their attention on maintaining balance before a task in which equilibrium is challenged is initiated. It is thought this strategy allows people to use frontal cortical systems to regulate stability, rather than rely upon the impaired basal ganglia mechanisms (Bilney et al., 2003a). Training the person with HD to step in response to perturbations, with an emphasis on speed and accuracy of the stepping strategy, is also recommended. Balance training may be enhanced through the use of auditory and visual cueing. To address inability to attend to more than one task at a time, interventions could include instruction to attend to one task at a time (Delval et al., 2008b). People at high risk of falls should be taught to break down complex activities into simple tasks and to focus their attention on performing each task separately; alternatively, having people with HD practise doing two activities at the same time under various practice and context conditions, may be a beneficial component to balance training (Delval et al., 2008b).

A major aim for therapeutic intervention in HD is for therapists to teach people with HD how to effectively bypass damaged basal ganglia structures and use frontal neural pathways to control movement (Bilney et al., 2003a, 2003b). This involves accessing the motor system by the patient responding to a visual or auditory input (which occurs through frontal pathways), rather than self-initiating movement (which occurs through the basal ganglia-cortical pathway). Sensory cueing involves the use of augmented sensory information, typically in the form of external visual, auditory or manual cueing, to improve performance in a task. There is some controversy as to whether individuals with HD can benefit from rhythmic auditory cues to improve gait characteristics (Delval et al., 2008a; Thaut et al., 1999). Synchronizing gait to rhythmic cues from a metronome (but not music) has been shown to assist the modulation of gait speed in people with HD (Thaut et al., 1999); however, under dual task conditions metronome cues may be less helpful due to attentional deficits in people with HD (Delval et al., 2008a).

Later stage management

As the disease progresses, compensatory strategies such as using sensory cues or attentional strategies can be implemented. Assistive devices (walker with wheels is preferred) and safety equipment, such as a helmet or elbow and knee protectors, may be recommended. Because cognitive impairments also increase in number and severity as the disease progresses, additional compensatory strategies, such as providing cues with goal-directed feedback, teaching skills using one-step commands and providing treatment in a quiet, non-distracting environment should also be considered. Practice should take place through repetition, allowing sufficient time for the person with HD to understand what is required of them and with key points continually being reinforced (Rao et al., 2005).

Assessment of the home, work and community environments in which the person with HD must function should be conducted and modifications made accordingly; in addition, prescription of assistive devices, home-adaptive equipment or modifications may be required. It is critical that the physiotherapist considers the nature of the disease process when considering devices and adaptive equipment. As functional status may be constantly changing, assessment should incorporate both the immediate and the longer-term need. It is important for the therapist to consider equipment that is adaptable to a patient’s changing condition. Standard walkers and four-point canes are difficult to manoeuvre and can interfere with natural gait pattern. As balance impairments progress in the middle stages of the disease, a rollator walker with four swivel wheels, and either hand or push-down breaks is often recommended. Walking sticks can be hazardous for patients with excessive choreic movements. Specialized seating needs should be considered; this may include increased seat-back height and depth, tilt and appropriate foot support. Hard surfaces and edges of assistive devices and wheelchairs should be protected with padding where necessary. Choosing the right kind of adaptive equipment is a collaborative process. Balancing independence and safety requires special consideration for each person’s individual needs (Rao et al., 2005). Use of certain devices and equipment, such as those described above, may provide the necessary support to maximize a person’s functional abilities.

Protective techniques are often used for people with HD, who have an increased risk of bruising and fractures due to involuntary choreic movements. People with HD may benefit from protective padding on the elbow, forearms knees and shins to minimize injury. In order to maximize a patient’s ambulatory independence, a therapist may recommend use of a helmet and other body padding as the disease progresses. A helmet may prevent serious head injury in case of a fall, and therefore allows a patient who might otherwise be considered ‘unsafe’ the opportunity to continue to ambulate independently. Restraint should be kept to a minimum; uncontrolled movements should be minimized as far as possible by considering posture and positional changes.

Respiratory problems may develop at any stage but are more likely to occur in the late-middle and late stages of the disease when mobility becomes more limited. Rigidity, bradykinesia and dystonia eventually lead to immobility and dependence for all care in people with HD (Ribchester et al., 2004). Immobility and postural changes may result in decreased respiratory function (Lin et al., 2006). As with many progressive neurological conditions, the major cause of death in HD is respiratory failure (Lanska et al., 1988; Sørensen & Fenger, 1992) due to factors such as weakened respiratory muscles and/or swallowing problems.

Respiratory interventions, such as deep breathing exercises, body positioning to optimize ventilation–perfusion,modified postural drainage, and airway clearance techniques may be required for specific respiratory problems (see Ch. 15). Caregivers may be taught assisted coughing techniques and a suction machine should be made available for patients who have difficulty clearing secretions. Educating caregivers regarding the signs of aspiration is also important.

Palliative care

Palliative care services have an important role in helping people with HD and their families to prepare for the later stages of HD (Moskowitz & Marder 2001; Travers et al., 2007). The ultimate aim for palliative care is to achieve the best possible quality of life for patients and their families. To this end, coordinated management of the physical and cognitive effects of disease progression is essential. The physiotherapist can advise on seating and positioning, respiratory management, as well as relaxation techniques. It should be noted that the use of feeding tubes in patients with dementia is controversial (Cervo et al., 2006); a recent report provides a comprehensive review of the issues involved in the use of feeding tubes for patients with neurological disease which should be patient centred and not based on the convenience of staff or carers (Royal College of Physicians and British Society of Gastroenterolgists, 2010). Obtaining a patient’s views of feeding tubes and end-stage care is better discussed and recorded at a time before they lose capacity (Simpson, 2007).

CASE HISTORY 1: Early-stage Huntington’s disease

The following case history is modified with permission from Smith et al. (2007).

CASE HISTORY 2: Home-based physiotherapy in mid-stage Huntington’s disease

The following case history is modified from Quinn and Rao (2002).

CASE HISTORY 3: Late-stage Huntington’s disease