Motor Abnormalities

Early in the course of the disease, many patients with parkinsonism are unaware of any motor deficit. Often the patient’s spouse comments on a reduction in facial expression (often misinterpreted as depression), a reduction in arm swing while walking, and a slowing of activities of daily living, most notably dressing, feeding, and walking. The patient may then become aware of a reduction in manual dexterity, with slowness and clumsiness interfering with activities. PD is typically asymmetrical, especially early in the course. A painful shoulder is one of the most common early symptoms of incipient unilateral rigidity and bradykinesia. This symptom, probably related to decreased arm swing and secondary joint changes or shoulder muscle rigidity, is often misdiagnosed as bursitis, arthritis, or a rotator cuff disorder. All recreational and work tasks, household chores, and self-care functions eventually become impaired. Handwriting often becomes slower and smaller (micrographia), with speed and size decreasing as the task continues. Eventually the writing may become illegible. Use of eating utensils becomes difficult, chewing is laborious, and choking while swallowing may occur. If the latter is an early and prominent complaint, one must consider bulbar involvement in one of the parkinsonism-plus syndromes, such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) (Stefanova et al., 2009; Williams and Lees, 2009) (Table 21.2). Dressing tasks such as fastening small buttons or getting arms into sleeves are often difficult. Hygiene becomes impaired. As with most other tasks, disability is greater if the dominant arm is more affected; shaving, brushing teeth, and other repetitive movements usually are affected the most.

Speech becomes slurred and loses its volume (hypophonia), and as a result, patients often must repeat themselves. Like gait, speech may be festinating; that is, it gets faster and faster (tachyphemia). A large number of additional speech disturbances may occur, including stuttering and palilalia, involuntary repetition of a phrase with increasing rapidity. Early, pronounced voice changes often indicate a diagnosis other than PD (e.g., palilalia is more commonly a feature of PSP and MSA). A harsher, nasal quality of the voice, which is quite distinctive from the hypophonic monotone of PD, also suggests the diagnosis of PSP. A higher-pitched quivering, “whiny” voice may suggest MSA, especially if it is associated with frequent sighing, respiratory gasps, laryngeal stridor, and other respiratory problems (Mehanna and Jankovic, 2010).

Another problem related to impairment of bulbar function is excessive salivation and drooling. Initially this may occur only at night, but later it can be present throughout the day, at times necessitating the constant use of a tissue or handkerchief.

Getting in and out of a chair or car and climbing in and out of the bathtub cause problems; patients often switch to showering. Many patients misinterpret these difficulties as resulting from “weakness.” Generalized loss of energy and easy fatigability are also common complaints. Walking becomes slowed and shuffling, with flexion of the knees and a narrow base. When involvement is asymmetrical, one leg may drag behind the other. Stride then shortens, and turns include multiple steps (turning en bloc). Later, patients may note a tendency to advance more and more rapidly with shorter and shorter steps (festination), at times seemingly propelled forward with a secondary inadequate attempt to maintain the center of gravity over the legs. When this occurs, a nearby wall or an unobstructed fall may be the only method of stopping. Alternatively, the feet may seem glued to the floor, the so-called freezing phenomenon, or motor block. Early on, this is appreciated when the patient initiates walking (start hesitation), is turning (especially in an enclosed space), or attempts to walk through an enclosed area such as a doorway (an elevator door is a common precipitant). When combined with poor postural stability, prominent freezing results in the tendency to fall forward or to the side while turning. Later, impaired postural reflexes may cause falls without a propulsive or freezing precipitant. The early occurrence of falls suggests a diagnosis of PSP or other parkinsonian disorder rather than PD. Turning over in bed and adjusting the bedclothes often become difficult. Patients may have to sit up first and then turn, and later the spouse may have to help roll the person over or adjust position for comfort.

Cognitive, Autonomic, and Sensory Abnormalities

The complaints of patients with parkinsonism are not limited to the motor system, and a large variety of nonmotor symptoms, many of which are probably not directly related to dopaminergic deficiency, often emerge as the disease progresses. In many cases, they become more disabling than the classic motor problems (Lim et al., 2009) (see Table 21.2). Dementia occurs in a variety of parkinsonian syndromes (see Chapters 66 and 72). Depression is also a common problem, and patients often lose their assertiveness and become withdrawn, more passive, and less motivated to socialize. The term bradyphrenia describes the slowness of thought processes and inattentiveness often seen.

Complaints related to autonomic dysfunction are also common. In all parkinsonian syndromes, constipation is a common complaint and may become severe. However, fecal incontinence does not occur in PD unless the motor disability is such that the patient cannot maneuver to the bathroom, dementia is superimposed, or impaction has led to overflow incontinence. Bladder complaints such as frequency, nocturia, and the sensation of incomplete bladder emptying may occur. Urinary incontinence is especially suggestive of MSA. A mild to moderate degree of orthostatic hypotension is common in parkinsonian disorders, and antiparkinsonian drugs often aggravate the problem (see Chapter 71). If the autonomic features, particularly erectile dysfunction, sphincter problems, and orthostatic lightheadedness, occur early or become the dominant feature, one must consider the possibility of MSA (see Chapter 66). Impotence with early loss of nocturnal or morning erections and inability to maintain erection during intercourse is suggestive of MSA. The other symptom that may precede the onset of motor problems associated with several parkinsonian disorders, particularly PD, MSA, or dementia with Lewy bodies, is rapid eye movement (REM) sleep behavior disorder. One characteristic nonmotor feature of PD is excessive greasiness of the skin and seborrheic dermatitis, characteristically seen over the forehead, eyebrows, and malar area.

Visual complaints are usually not a prominent feature, with the following specific exceptions. In PD (and many other parkinsonian disorders), diplopia may occur during reading secondary to impaired convergence. Visual complaints sometimes occur in other parkinsonian disorders, particularly PSP (see Chapter 71). Oculogyric crises, which are sudden episodes of involuntary ocular deviation (most often up and to the side) in the absence of neuroleptic drug exposure, are virtually pathognomonic of parkinsonism after encephalitis lethargica, although they may occur in rare neurometabolic disorders as well. Sensory loss is not part of parkinsonism, although patients with PD may have poorly explained positive sensory complaints such as numbness and tingling, aching, and painful sensations that are sometimes quite disabling. Peripheral neuropathy suggests another disorder or an unrelated problem (e.g., diabetes mellitus), although recent evidence suggests a higher-than-expected incidence of peripheral neuropathy, possibly related to levodopa treatment and elevated methylmalonic acid levels (Toth et al., 2010).

Although a variety of neurophysiological and computer-based methods have been proposed to quantitate the severity of the various parkinsonian symptoms and signs, most studies rely on clinical rating scales, particularly the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr staging scale, and Schwab and England Activities of Daily Living Scale (Box 21.2). Non-demented patients can reliably self-administer and complete the historical section of the UPDRS, now available in a revised version referred to as the Movement Disorder Society (MDS)-UPDRS (www.movementdisorders.org). The revision clarifies some ambiguities and more adequately assesses the nonmotor features of PD, which are among the most disabling symptoms, particularly in more advanced stages of the disease (Goetz et al., 2008). Some clinical research studies supplement the UPDRS by a more objective timed test such as the Purdue Pegboard Test and movement and reaction times. Many scales, such as the Parkinson’s Disease Questionnaire-39 (PDQ-39) and the Parkinson’s Disease Quality of Life Questionnaire (PDQL), attempt to assess the overall quality of life (Jankovic, 2008).

Onset and Course

As in other movement disorders, the age at onset of a parkinsonian syndrome is clearly important in considering a differential diagnosis. Although the majority of patients are adults, parkinsonism does occur in childhood (see Box 21.1). PD usually has a slow onset and very gradual progression (Jankovic, 2005). Generally, patients with early-onset PD and those with a tremor-dominant form tend to progress at a slower rate and are less likely to have an associated cognitive decline than those with postural instability and the gait difficulty form of PD. Other disorders (e.g., those due to toxins, cerebral anoxia, infarction) may present abruptly or progress more rapidly (resulting in so-called malignant parkinsonism) or may even improve spontaneously (e.g., those due to drugs, multiple infarcts, certain forms of encephalitis).

Examination and Clinical Signs

The diagnosis of parkinsonism often is immediately apparent on first contact with the patient. The facial expression, low-volume voice, tremor, poverty of movement, shuffling gait, and stooped posture provide an immediate and irrevocable first impression of parkinsonism. However, the physician must perform a detailed assessment, searching for any atypical features in attempting to distinguish between PD and other parkinsonian disorders. Loss of facial expression (hypomimia) often is an early sign of PD. But occasional patients have a wide-eyed, anxious, worried expression due to furrowing of the brow (“procerus sign”) and deep facial folds, which strongly suggests PSP. Blink frequency usually is reduced, although blepharoclonus (repetitive spasms of the lids on gentle eye closure) and reflex blepharospasm (e.g., precipitated by shining a light into the eyes or manipulating the lids) also may be seen. Spontaneous blepharospasm and apraxia of lid opening occur less often. Patients with apraxia of lid opening (not a true apraxia) often open their eyes using their hands, and once the eyes are fixated on an object, the eyelids remain open. Primitive reflexes, including the inability to inhibit blinking in response to tapping over the glabella (Myerson sign) and palmomental reflexes, are nonspecific and are commonly present in many parkinsonian disorders (Brodsky et al., 2004).

Various types of tremor, most notably resting and postural varieties, often accompany parkinsonian disorders. Patients should be observed with hands resting on their laps or thighs, and they should be instructed to hold their arms in an outstretched position or in a horizontal position with shoulders abducted, elbows flexed, and hands palms-down in front of their faces in the so-called wing-beating position. Resting tremor often reemerges after a period of quiescence in a new position (re-emergent tremor) (Jankovic, 2008). This re-emergent tremor may be wrongly attributed to postural tremor and lead to misdiagnosis as essential tremor. A true kinetic (intention) tremor, elicited by the finger-to-nose maneuver, is much less common in patients with PD and other parkinsonian disorders and usually indicates involvement of cerebellar connections. A jerky postural tremor indicative of additional myoclonus is suggestive of a diagnosis of MSA rather than PD. Head tremor (titubation) suggests a diagnosis other than PD, such as essential tremor, dystonic neck tremor, or a cerebellar tremor associated with the cerebellar form of MSA (MSA-C), spinocerebellar atrophy, or multiple sclerosis (MS).

Rigidity is an increase in muscle tone, usually equal in flexors and extensors and present throughout the passive range of movement. This contrasts with the distribution and velocity-dependent nature of spasticity. Paratonia (or Gegenhalten), on the other hand, increases with repetitive passive movement and attempts to get the patient to relax. It may be difficult to distinguish between milder forms of paratonia and rigidity, especially in the legs. Characteristically, the performance of voluntary movements in the opposite limb (e.g., opening and closing the fist or abduction-adduction of the shoulder) brings out rigidity, a phenomenon known as activated rigidity (Froment sign). Superimposed on the rigidity may be a tremor or cogwheel phenomenon. This, like the milder forms of rigidity, is better appreciated by placing one hand over the muscles being tested (e.g., placing the left thumb over the biceps and the remaining fingers over the triceps while flexing and extending the elbow with the right hand). The distribution of the rigidity sometimes is helpful in differential diagnosis. For example, pronounced nuchal rigidity with much less hypertonicity in the limbs suggests the diagnosis of PSP, whereas an extreme degree of unilateral arm rigidity or paratonia suggests corticobasal degeneration (CBD) or corticobasal syndrome (CBS). The latter term is suggested for cases diagnosed clinically, as only 24% of such cases have pathologically proven CBD (Ling et al., 2010).

Akinesia and bradykinesia are appreciable on examination in several ways. Automatic movements normally expressed in conversation, such as gesturing with hands while speaking, crossing and uncrossing the legs, and repositioning the body in the chair diminish or are absent. The performance of rapid, repetitive, and alternating movements such as finger tapping, opening and closing the fist, pronation-supination of the forearm, and foot tapping is slow, with a gradual reduction in amplitude and eventual cessation of movement (freezing). In addition to fatiguing, there may be hesitation in initiating movement and arrests in ongoing movement. The severely afflicted patient may be barely able to perform the task. There is a tendency for rapid repetitive movements to take on the frequency of an accompanying tremor. In such cases, instruct the patient to slow the movement and attempt to complete it voluntarily. Watching the patient write is an important part of the examination. Observation may reveal great slowness and effort, even in someone with minimal change in the size of the script. In addition to micrographia, writing and drawing show a tendency to fatigue, with a further reduction in size as the task proceeds and a concomitant action tremor.

Postural disturbances are common in parkinsonian disorders. The head usually tilts forward and the body becomes stooped, often with pronounced kyphosis and varying degrees of scoliosis (Ashour and Jankovic, 2006). The arms become flexed at the elbows and wrists, with varying postural deformities in the hands, the most common being flexion at the metacarpophalangeal joints and extension at the interphalangeal joints, with adduction of all the fingers and opposition of the thumb to the index finger (striatal hand). Flexion also occurs in the joints of the legs. Variable foot deformities occur, the most common being hammer toe–like disturbances in most of the toes, occasionally with extension of the great toe (striatal foot), which may be misinterpreted as an extensor plantar response. Initially, abnormal foot posturing may be induced by action, occurring only during walking or weight bearing. The flexed or simian posture sometimes is extreme, with severe flexion at the waist (camptocormia) (Azher and Jankovic, 2005; Jankovic, 2010). Some patients, particularly those with MSA, exhibit scoliosis or tilted posture (Pisa sign). Despite the truncal flexion, the position of the hands in patients with PD often remains above the beltline because of flexion of the elbows. Occasional patients remain upright or even demonstrate a hyperextended posture. Hyperextension of the neck is particularly suggestive of PSP, whereas extreme flexion of the neck (head drop or bent spine) suggests MSA but also PD.

Postural instability is characteristic of parkinsonian disorders, particularly the postural instability and gait difficulty forms of PD, PSP, and MSA. As patients rise from a sitting position, poor postural stability, slowness, narrow base, and not repositioning the feet often combine to cause them to fall back into the chair “in a lump.” PSP patients may “rocket” out of the chair inappropriately quickly, failing to recognize their inability to maintain stability on their feet. The PD patient may require several attempts, push off the arms of the chair, or need to be pulled up by an assistant. Gait disturbances in typical parkinsonism include lack of arm swing, shortened and later shuffling stride, freezing in the course of walking (especially at a door frame or when approaching a potential obstruction or a chair), and in more severe cases, propulsion and spontaneous falls (Jankovic, 2007a). In addition, walking often brings out or exacerbates a resting tremor. To assess postural instability, the physician performs the pull test. Standing behind the patient, the examiner pulls the patient backward by the shoulders (or by a hand on the sternum), carefully remaining close behind to prevent a fall. Once postural reflexes are impaired, there may be retropulsion or multiple backward steps in response to the postural perturbation. Later there is a tendency to fall en bloc without retropulsion or even normal attempts to recover or to cushion the fall.

In PD, the base of the gait is usually narrow, and tandem gait is performed well. When the gait is wide-based, a superimposed ataxia is a consideration, as is seen in MSA-C, although some of the spinocerebellar atrophies may present with parkinsonism and ataxia (see Chapter 72). Toe walking (cock-walk) is seen in some parkinsonian disorders (e.g., due to manganese poisoning), and a peculiar loping gait may indicate the rare patient with akinesia in the absence of rigidity, which may be one phenotype of PSP. The so-called magnetic foot, or marche à petits pas, of senility (also seen in multiple infarctions, Binswanger disease, and normal pressure hydrocephalus) more commonly results in a lower-body parkinsonism, typically associated with cerebrovascular disorders such as lacunar strokes. A striking discrepancy of involvement between the lower body and the upper limbs, with normal or even excessive arm swing, is an important clue to the diagnosis of vascular parkinsonism.

Differential Diagnosis

Although dementia commonly occurs in PD, this feature, particularly when present relatively early in the course, must alert the physician to other possible diagnoses (see Chapter 66), including the coincidental association of unrelated causes of cognitive decline (Galvin et al., 2006). Prominent eye movement disturbances are found in a number of conditions, including PSP, MSA-C, postencephalitic parkinsonism, and CBD. It is important to assess not only horizontal and vertical gaze (typically impaired in PSP) but also optokinetic nystagmus to note whether vertical saccadic eye movements (particularly as the optokinetic tape moves in upward direction) are impaired, as in PSP. The oculocephalic (doll’s eye) maneuver must be performed where ocular excursions are limited, seeking supportive evidence of supranuclear gaze palsy. Patients with PSP typically have trouble making eye contact because of disturbed visual refixation. As a result of persistence of visual fixation when PSP patients turn, their head turn lags behind their body turn. Obvious pyramidal tract dysfunction usually suggests diagnoses other than PD. An exaggerated grasp response indicates disturbance of the frontal lobes and the possibility of a concomitant dementing process. Occasionally a pronounced flexed posture in the hand may be confused with a grasp reflex, and the examiner must be convinced that there is active contraction in response to stroking of the palm. The abnormalities of rapid, repetitive, and alternating movements described earlier can be confused with the clumsy awkward performance of limb-kinetic apraxia (Zadikoff and Lang, 2005). More importantly, the abnormalities in performance of repetitive movement must not be confused with the disruption of rate, rhythm, and force typical of the dysdiadochokinesia of cerebellar disease. A helpful maneuver in testing for the presence of associated cerebellar dysfunction is to have the patient tap with the index finger on a hard surface. Watching and, in particular, listening to the tapping often allows a distinction to be made between the slowness and decrementing response of parkinsonism and the irregular rate and force of cerebellar ataxia. Testing for ideomotor apraxia, as seen in CBS, should also be performed by asking the patient to mimic certain hand gestures (intransitive tasks) such as the “victory sign” or the University of Texas “hook ’em horns sign” (extension of the second and fifth finger and flexion of the third and fourth finger) or to simulate certain activities (transitive tasks [using a tool or utensil]) such as brushing teeth and combing hair. However, in the later stages of many parkinsonian disorders, rigidity and other motor disturbances may make results of these tests difficult to interpret. In PD or MSA, the less affected limb may show mirror movements as the patient attempts to perform rapid repetitive or alternating movements with the most affected limb (Espay et al., 2005). On the other hand, in CBS, the most affected limb may mirror movements performed in the less affected limb. Some patients with parkinsonism and frontal lobe involvement exhibit signs of perseveration such as the applause sign, manifested by persistence of clapping after instructing the patient to clap consecutively three times as quickly as possible. Although initially thought to be characteristic of PSP, it is also present in some patients with other parkinsonian disorders (Wu et al., 2008).

The presence of other abnormal movements in an untreated patient may indicate a diagnosis other than PD. Seek stimulus-sensitive myoclonus by using light touch or pinprick in the digits and the proximal palm or the sole of the foot. Easily elicited and nonfatiguing myoclonic jerks in response to these stimuli may be seen not only in patients with CBS and MSA but also in patients with PD and dementia.

Despite a variety of sensory complaints, patients with PD do not show prominent abnormalities on the sensory examination, aside from the normal increase in vibration threshold that occurs with age. Cortical sensory disturbances suggest a diagnosis of CBS. Wasting and muscle weakness are not characteristic of PD, although later in the course of the disease, severely disabled patients show disuse atrophy and severe problems in initiating and maintaining muscle activation that are often difficult to separate from true weakness. Combinations of upper and lower motor neuron weakness occur in several other parkinsonian disorders (see Table 21.2).

Assess autonomic function. At the bedside, this includes an evaluation of orthostatic changes in blood pressure and pulse (in supine position and at least 3 minutes after standing) and, in appropriate circumstances, the patient’s response to the Valsalva maneuver, mental arithmetic, and the cold pressor test, among others. Finally, perform sequential examinations over time, carefully searching for the development of additional findings that may provide a clue to the diagnosis. Several parkinsonian syndromes present initially as pure parkinsonism; only later with disease progression do other signs develop.