Degenerative Movement Disorders of the Central Nervous System

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Chapter 51 Degenerative Movement Disorders of the Central Nervous System

Movement disorders are clinical manifestations of the loss of modulatory influence by the extrapyramidal system. These syndromes result in the appearance of involuntary movements such as tremor, chorea, and dystonia. Degenerative central nervous system movement disorders that are commonly encountered in the rehabilitation arena include Parkinson disease, Huntington disease, the hereditary ataxias (primarily Friedreich ataxia), hereditary spastic paraparesis, dystonia, and Tourette syndrome. Parkinson disease is by far the most common, affecting 1% to 2% of the population older than 65 years.51 This chapter discusses the diagnosis of, medical management of, and specific therapeutic approaches for these disorders. Particular attention is paid to rehabilitative interventions.


Normal volitional control of movement depends on a balanced relationship between the cortical, subcortical (extrapyramidal), cerebellar, spinal, and peripheral nervous systems. Movement disorders can develop from any malfunction within the extrapyramidal system (basal ganglia, subthalamic nucleus, substantia nigra, and red nucleus). Basal gangliar function is integral to movement by influencing the direction, amplitude, and course of the movement.38,39

Parkinson Disease

Clinical Presentation

The classic features of Parkinson disease include resting tremor, rigidity, postural instability, and bradykinesia. The resting tremor is the most common presenting symptom. It typically appears as a “pill-rolling” motion of the hand at 3 to 5 Hz. The resting tremor is suppressed by activity or sleep, and is intensified by stress or fatigue.

The rigidity of Parkinson disease can take two forms: “lead pipe” and cogwheeling. Lead pipe rigidity is frequently described as a smooth resistance to passive movement that is independent of velocity (in contradistinction to spasticity, which is velocity dependent). The lead pipe tone of one limb increases if another limb is involved in a voluntary motion or a mental task. Cogwheel rigidity is a ratcheting through the range of motion. It is caused by a subtle tremor superimposed on the rigidity.25

Posture is also affected, as patients with Parkinson disease frequently assume a position that is slumped over and forward with protracted shoulders, and flexed hips and knees. In older texts this was referred to as a simian posture. Postural reflexes are commonly affected in Parkinson disease, which can result in an increased tendency to fall backward or to the side.

Bradykinesia refers to slowness of motion. It can be reflected in an inability to change direction while walking, difficulty walking around an object, or just difficulty standing. When the bradykinesia affects the muscles of facial expression, a masked facies can be apparent (also known as hypomimia).54


The diagnosis of Parkinson disease is primarily clinical. Casual observation of the patient typically reveals the tremor or paucity of spontaneous movements. Resistance to movement of the limbs can be assessed during the range-of-motion examination. Motor examination often shows that Parkinson disease findings are asymmetric in the early stages of the disease. Gait observation should include linear motion as well as changes in direction. If a patient uses more than five steps to complete a 180-degree turn, the diagnosis of Parkinson disease should be considered.68 Fatigue in patients with Parkinson disease is common.5 Gait dysfunction contributes to the increased energy cost of walking.6 This can add to the elevated level of fatigue that is characteristic of individuals with Parkinson disease. Bedside cognitive evaluation can be normal early in the disease process, with neuropsychologic evaluation usually reserved for problematic cases. Routine electrodiagnostic studies do not aid in the diagnosis of Parkinson disease, except for exclusion of other neurologic processes. Investigational use of electrodiagnostic studies in Parkinson disease can be done in a research setting. The use of laboratory or neuroimaging investigations is for exclusionary indications and for atypical cases. At present, functional neuroimaging techniques such as positron emission tomography and single-photon emission computed tomography scanning are mainly experimental techniques. Both of these have emerged as significant investigational tools in some clinical trials.

The initial diagnosis of Parkinson disease can be delayed, depending on which symptoms predominate. The rigidity of Parkinson disease can be mistaken for the stiffness of arthritis. The postural changes can be attributed to osteoporosis or degenerative spine disease. The bradykinesia and masklike facies can be mistaken for depression. The differential diagnosis is wide (Box 51-1), as one should consider that the symptoms could also be induced by a drug, toxic, metabolic, or other neurologic process.

It is also helpful to watch for certain cardinal symptoms, such as early vertical eye movement abnormalities (progressive supranuclear palsy), early autonomic failure (Shy-Drager syndrome) or hyperreflexia, Babinski’s sign, ataxia, and peripheral neuropathy (multisystem degeneration).

Parkinsonism can manifest itself in multiple ways that can lead to disability. Patients with Parkinson disease have a high prevalence of both obstructive and restrictive pulmonary disease. This impairment is clinically relevant, in that Parkinson disease patients with respiratory disease have a decrement in activities of daily living compared with those with normal pulmonary function.52 The loss of muscle flexibility combined with the kyphotic posture is thought by some to contribute to the respiratory difficulty.57 The speech in a patient with Parkinson disease can be rapid and monotonous, and have low volume with poor articulation and inappropriate periods of silence. Handwriting can become small and cramped (micrographia). As Parkinson disease advances, dementia and depression can occur.3 Autonomic dysfunction with increased salivation, drooling, orthostasis, increased perspiration, constipation, hyperreflexic bladder with incontinence, dysphagia, and erectile dysfunction can also be present.4


From a prognostic point of view, tremor-predominant patients tend to progress at a slower pace than those individuals with gait or postural instability as a primary complaint.43 Tremor in general is not considered as disabling as bradykinesia. Akinesia can portend a more rapidly progressing disease process.31 Positive prognostic indicators include early tremor, rigidity, and a family history of Parkinson disease. Negative prognostic indicators include bradykinesia, akinesia, postural instability, gait dysfunction, cognitive deficits, and late age of onset. Laboratory, radiologic, or physiologic studies to date have not improved our prognostic acumen. Medical treatment, such as with levodopa, can affect quality of life.67 Treatment with carbidopa-levodopa can improve quality of life in the short-term, but long-term use can be associated with the reemergence of symptoms, which adversely affects the quality of life. Life expectancy is variable,43 but significantly improved with medical management.47 Dysphagia is considered the most important risk factor associated with early death.

Medical Management

Pharmacologic treatments of Parkinson disease intervene with three different aspects of the disease: slowing of disease progression, symptomatic relief of motor symptoms, and amelioration of nonmotor manifestations. At times, additional medications are required to address the adverse effects of antiparkinsonian treatments.

Several agents have been touted as neuroprotective agents in Parkinson disease, but no single drug is universally accepted as disease modifying. The antioxidant vitamin E failed to demonstrate benefits in a large multicenter trial. Another antioxidant, coenzyme Q10, was shown to delay the onset of the need for levodopa treatment in one multicenter study involving 80 patients. The investigators of this study cautioned that their results needed replication in larger studies. Selegiline, a selective monoamine oxidase B inhibitor, was purported to be a neuroprotective entity, but it is currently considered more of a symptomatic agent. Similarly, although dopamine agonists have demonstrated some positive neuroprotective effects on functional neuroimaging examinations, their effect on clinical progression is controversial. Recent research with pramipexole and ropinirole has shown the most promise. Small trials using an infusion of glial cell line–derived neurotrophic factor into the central nervous system have shown conflicting results.56

Symptomatic treatment of motor dysfunction has been the traditional medical intervention of Parkinson disease. The two main classes of drugs are dopamine replacements and dopamine agonists. Amantadine has weak antiparkinsonism effects. Anticholinergic medications are occasionally used in younger patients with tremor-predominant disease. Both amantadine and anticholinergic agents are relatively minor contributors to the Parkinson disease armamentarium. Levodopa is a keystone of Parkinson disease treatment. It is decarboxylated to dopamine. Levodopa is typically administered with a peripheral decarboxylase inhibitor such as carbidopa. This combination therapy results in less peripheral availability of dopamine (with a concomitant decrease in peripherally based side effects such as nausea) and increased central nervous system dopamine penetration.

Long-term levodopa treatment is complicated by two challenging clinical entities: motor fluctuations and dyskinesias. Motor fluctuations are a wearing-off phenomenon in which patients notice increased tremor and bradykinesia at the end of a dosing cycle. The predictability of these drop-off periods lessens as the disease progresses.59 Younger patients seem particularly vulnerable to motor fluctuations. Treatment strategies for motor fluctuations include dietary interventions and variable dosing schedules. Dyskinesias usually take the form of chorea, but painful dystonias and myoclonus can also occur. Psychiatric symptoms, including florid psychosis, can be observed with levodopa use. Levodopa usually demonstrates high usefulness initially, but when used chronically it tends to have reduced therapeutic effectiveness.3

Because of the potential problems with levodopa therapy, some clinicians choose to use a dopamine agonist as an initial treatment strategy. Agents in this class include pergolide, pramipexole, and ropinirole. Although these medications often have less therapeutic efficacy than levodopa, they rarely cause dyskinesia. As noted, there is some suggestion that these agents might have a neuroprotective effect on disease progression. Side effects of dopamine agonists include nausea, vomiting, orthostatic hypotension, and psychiatric symptoms. Because patients can have individualized responses to these agents, switching between medications in this class is commonly done. Another factor that might have clinical relevance is that these agents are more expensive than levodopa therapy. Because of their potential disease-modifying effects and their enhanced utility in mild disease, these agents might be also the preferred drugs in younger and healthier individuals. One randomized trial supported either levodopa or pramipexole as a reasonable option for initial therapy in Parkinson disease, but each drug was associated with different efficacies and adverse effect profiles.21

Nonmotor symptoms of Parkinson disease, such as orthostasis, sphincter dysfunction, and depression, are also targets for pharmacologic intervention. Treatment options for orthostasis include increased salt and water intake, or the use of midodrine or fludrocortisone. Neurogenic bowel function in Parkinson disease usually presents as constipation, and is amenable to treatment with increased hydration, bulk-forming agents including dietary fiber, stool softeners, and chemical or mechanical rectal stimulation. Hyperreflexive bladder activity can be treated with anticholinergic agents or α-adrenergic blocking agents, although both classes can exacerbate orthostasis. Depression is usually addressed with selective serotonin reuptake inhibitors, but therapy needs to be carefully monitored, because there are reports that these agents have worsened Parkinson disease symptoms. Venlafaxine might be particularly useful because this agent can increase blood pressure. Tricyclic antidepressants can be considered, but one should choose one with low anticholinergic side effects, such as desipramine. Differences in effectiveness between the classes of antidepressants for patients with Parkinson disease have yet to be demonstrated.61

Rationale for Rehabilitation

Although rehabilitation services are often given to the patient with Parkinson disease, this occurrence is based more on common practice rather than clear research data.22,34,64 There is a paucity of well-designed research studies looking at specific rehabilitation techniques. The existing literature is both sparse and fraught with confounding variables such as changes in medication regimens. A recent review examined 11 studies involving various physical therapy techniques in Parkinson disease. The authors found insufficient evidence to support or refute the efficacy of any form of physical therapy over another form.10 There was also insufficient evidence found to support the efficacy of any therapy compared with no therapy. Perhaps the best designed study was a prospective randomized crossover investigation of 4 weeks of outpatient physical therapy, in which medication changes were not allowed. This study demonstrated significant improvement in activities of daily living and motor function, but no improvement in tremor, mentation, and mood. These improvements returned to baseline 6 months after termination of the intervention. Long-term rehabilitation programs have been advocated, but the stability of the benefits gained in these programs has not been demonstrated.42

Exercise and Muscle Physiology

When prescribing an exercise program, one has to take into account the patient’s underlying physical condition. Patients with Parkinson disease appear to exercise with decreased metabolic and mechanical efficiency.26 This disadvantageous situation might be amenable to treatment with aerobic conditioning.53 It appears that prescribing conditioning exercises to patients with Parkinson disease is useful only in the setting of an optimized medication regimen. The specific exercises have not been proven or agreed on. It might also be difficult for patients with Parkinson disease to exercise with sufficient intensity to achieve a training effect.49 Careful attention to safety is needed when prescribing aerobic conditioning exercises, because patients with Parkinson disease are at high risk for falls. They typically require a supervised environment when using moving equipment such as a treadmill. Improvements in mood and dyskinesias have been reported with the use of aerobic conditioning.50 Neck tone has been found to play a significant role in the patient’s functional mobility,17 and abnormal postural tone is an important contribution to balance and mobility disorders in patients with Parkinson disease. Therapy geared toward this tone could be a key to treatment.

Psychosocial and Cognitive Concerns

Depression is common in patients with Parkinson disease, with an estimated prevalence of 47%.70 Some authors feel that depression significantly contributes to the cognitive dysfunction.33 Depression can be related to a deficit in serotonergic transmission25 or to diminished cortical levels of noradrenaline (norepinephrine) and dopamine.55 The presence of depression adds significant disability beyond that attributed to motor dysfunction.71

No individual psychologic technique appears to have superiority over another with respect to improvements of mood status. As discussed further below, mental imagery and biofeedback can play a part in improving motor performance during rehabilitation. Some of the techniques reported for mood dysfunction in patients with Parkinson disease include individual, group, and family counseling. Social impairments include loss of autonomy and isolation. Many centers have support groups that are useful in educating patients and their families. Antidepressants such as the serotonin reuptake inhibitors have also been used.

Declining cognitive ability often adds to the challenge of treating a patient with Parkinson disease.9 As the disease progresses, thought processes become more rigid and preservative. Dementia occurs in 10% to 15% of patients with Parkinson disease and has an increasing incidence with age. Subtle changes in cognition begin to occur even early in the course of Parkinson disease. Decline in motor function and cognitive decline often occur on a parallel course. Deficits in visual perception and verbal fluency have also been reported in some patients with Parkinson disease.44

There is little evidence supporting the therapeutic benefit of specific cognitive retraining techniques. The use of the mental imagery of a planned motor task has been purported to improve execution of function tasks, but this has not been fully validated.