Diagnosis and Assessment of Parkinson Disease and Other Movement Disorders

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 or even frozen shoulder is one of the most common early symptoms of PD, possibly related to decreased arm swing and secondary joint changes or shoulder muscle rigidity, often misdiagnosed as bursitis, arthritis, or a rotator cuff disorder. Indeed, many PD patients have a variety of joint (e.g., striatal hand or foot) and skeletal deformities (e.g., scoliosis, Pisa sign, camptocormia) which are often wrongly attributed to arthritis or orthopedic problems ( ). Besides shoulder pain as one example of a sensory symptom related to underlying motor abnormality, painful dystonia and other etiologies can contribute to pain and discomfort associated with PD ( ). Handwriting often becomes slower and smaller (micrographia), with speed and size decreasing as the task continues. Eventually the writing may become illegible. Dressing tasks such as fastening small buttons or getting arms into sleeves are often slow and difficult. Hygiene, including taking a shower or bath, 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. 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) ( ) ( Table 24.2 ).

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 , an involuntary repetition of a phrase with increasing rapidity. When hypophonia and speech problems occur as presenting symptoms or in early stage of the disease one should consider a diagnosis other than PD (e.g., hypophonia and palilalia are more common features of PSP and MSA, particularly when present early in the course, than of PD). A monotone, nasal quality of the voice, which is quite distinctive from the hypokinetic dysarthria 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 ( ).

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 also 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, may cause problems and most patients switch to showering instead of bathing. Many patients misinterpret these difficulties as resulting from “weakness,” but there is usually no evidence of weakness in PD until patients develop frailty related to physical inactivity. Generalized loss of energy and fatigability are among the most common complaints by patients with PD ( ). 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), especially when turning (particularly in an enclosed space), or attempts to walk through an enclosed area or a narrow passage such as a doorway or walking in or out of an elevator. 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.

Non-Motor Abnormalities

The complaints of patients with parkinsonism are not limited to the motor system, and a large variety of non-motor 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 ( ; see Table 24.2 ). Non-motor features can precede the motor abnormalities and these are increasingly recognized as important features during the prodromal (pre-motor) phase of PD ( ).

Cognitive decline and dementia occur in a variety of parkinsonian syndromes that are discussed elsewhere (see Chapter 96 ). 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 PD, even in the prodromal phase. 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 are also common. Urinary incontinence and bladder retention are especially suggestive of MSA. A mild to moderate degree of orthostatic hypotension is common in parkinsonian disorders, and antiparkinsonian drugs often aggravate the problem. 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. Impotence with early loss of nocturnal or morning erections and inability to maintain erection during intercourse is suggestive of MSA (see Chapter 46 ). 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 (see Chapter 101 ). One characteristic non-motor feature of PD is excessive greasiness of the skin and seborrheic dermatitis, characteristically seen over the forehead, eyebrows, and malar area.

In addition to pain, there are many other sensory symptoms associated with PD ( ). 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. 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 a higher-than-expected incidence of peripheral neuropathy, possibly related to levodopa treatment and elevated methylmalonic acid levels, has been suggested ( ).

Although a variety of neurophysiological and computer-based methods for quantitating the severity of the various parkinsonian symptoms and signs have been proposed, most studies rely on clinical rating scales. Non-demented patients can reliably self-administer and complete the Movement Disorder Society (MDS)-UPDRS ( http://www.movementdisorders.org ). The revision clarifies some ambiguities and more adequately assesses the non-motor features of PD ( ). Some clinical research studies also use more objective timed test such as the Purdue Pegboard Test, movement and reaction times, and a variety of wearable devices are increasingly used in clinical trials to provide another, more quantitative, assessment of motor function. 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 ( ).

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 may have onset in childhood or adolescence (juvenile parkinsonism) and between 21 and 40 years (young-onset parkinsonism; see Box 24.1 ). The younger the age at onset the more likely it is that the etiology of the parkinsonism is genetic. Besides categorizing patients with PD according to age at onset, there are other subtypes of PD. For example, the “tremor-dominant” subtype typically has a slow progression and more favorable long-term prognosis than the “postural instability gait difficulty” (PIGD) subtype which is more rapidly progressive and is more likely associated with non-motor problems including cognitive decline ( ). Other parkinsonian disorders (e.g., those due to toxins, vascular causes) may present abruptly or progress more rapidly or may even improve spontaneously (e.g., those due to drugs, 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, slowness and 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 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) are not able to open their eyes after spontaneous or voluntary closure and often must use their fingers to forcefully open their eyes, 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 ( ).

Various types of tremor, most notably rest 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.” Rest tremor often re-emerges after a period of quiescence in a new position ( re-emergent tremor ; ). This re-emergent tremor, which is often the most troublesome parkinsonian tremor because it interferes with holding objects steadily against gravity, 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 (myoclonic) postural tremor 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, an increase in muscle tone, is 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 (the clasp-knife phenomenon). 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 syndrome (CBS), diagnosed clinically, or corticobasal degeneration (CBD), diagnosed by autopsy ( ).

Bradykinesia (slow movement) or akinesia (absence of movement) 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) . The decrement in amplitude of repetitive movements is characteristic of the bradykinesia of PD and is often considered mandatory for the diagnosis. In contrast, bradykinesia in PSP may not be associated with decrementing amplitude on repetitive movements ( ). Watching the patient write is an important part of the examination. Observation of writing in a patient with PD may reveal great slowness and effort, even in someone with minimal change in the size of the script. In contrast, patients with PSP may have “fast micrographia” with a rapid production of an illegible 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. This is in contrast to handwriting in patients with essential tremor (ET), which tends to be larger and tremulous.

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, typically away from the side of the onset of parkinsonian signs, such as rest tremor. 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 ; Fig. 24.2, A ; ). Flexion with contracture may also occur in the joints of the legs, particularly the knees, contributing to the typical flexed posture. 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 ; see Fig. 24.2, B ), 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 ; ; see Fig. 24.2, C ). Some patients, particularly those with MSA, exhibit scoliosis or tilted posture ( Pisa sign ; see Fig. 24.2, D ). 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 (see Fig. 24.2, D ) but also PD.

Postural instability is characteristic of all 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, rigidity, narrow base, and not repositioning the feet often combine to cause them to fall back into the chair “in a lump”; this is especially prominent in patients with PSP. These patients also 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, narrow base, flexed knees, freezing in the course of walking (especially when initiating gait and when approaching a door frame or a potential obstruction or a chair). Patients with PD turn en bloc, whereas patients with PSP tend to pivot when they turn. In more severe cases of PD or PSP, propulsion and retropulsion may occur spontaneously, resulting in falls ( ). In addition, walking often brings out or exacerbates a hand tremor in patients with PD. To assess postural instability, the physician performs the pull test. Standing behind the patient, the examiner pulls the patient backward by the shoulders, 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 but when the gait is wide-based, atypical parkinsonism should be considered (see Chapter 96 ; ). 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, is typically seen in vascular parkinsonism, Binswanger disease, and normal pressure hydrocephalus. Lower-body parkinsonism in which the gait is slightly broad-based and shuffling (with possible freezing) but normal arm swing and minimal or no impairment in upper limbs is typically associated with a history or stroke risk factors and evidence of cerebrovascular disorders such as lacunar strokes, although some patients may have microinfarcts not necessarily appreciated on brain imaging ( ). 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 or normal pressure hydrocephalus.

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 96 ), including dementia with Lewy bodies, particularly if the cognitive deficit is accompanied by visual hallucinations and the course is fluctuating, or the coincidental association with other common causes of cognitive decline, such as Alzheimer disease ( ). Prominent eye movement disturbances are found in a number of conditions, including PSP, MSA-C, postencephalitic parkinsonism, CBD, and Machado-Joseph disease (SCA3). It is important to assess both horizontal and vertical pursuit and saccadic eye movements. Slowing of vertical saccades is characteristic of PSP and is particularly noticeable when evaluating vertical optokinetic nystagmus and the optokinetic tape moves in upward direction during which there is slowing or impairment of downward saccades ( ). The oculocephalic (doll’s eye) maneuver must be performed when 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 ( ). 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 (dysdiadochokinesia). Testing for ideomotor apraxia, as seen in CBS, also should 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 ( ). 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 ( ).

The presence of other abnormal movements in an untreated patient may indicate a diagnosis other than PD. Seek evidence of stimulus-sensitive myoclonus by producing a sudden loud noise or using a 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 some 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 24.2 ).

Assessing autonomic function is important not only in patients suspected of having MSA but also in patients with PD, many of whom have dysautonomia. 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.

Rest Tremor

A rest tremor occurs with the body part in complete repose and often dampens or subsides entirely with action. For this reason, patients with pure rest tremor experience greater social embarrassment than functional disability, unless, as noted earlier, the rest tremor re-emerges during postural holding. Indeed, in some cases it is a family member or friend who first observes the tremor, which is noticeable to the patient only later. Alternatively, some patients complain of the sensation of trembling inside long before a rest tremor becomes overt. Early on, rest tremor may be intermittent and often precipitated only by anxiety or stress. The onset of most types of tremor is in the arms, often beginning asymmetrically. In the face, rest tremor usually affects the tongue, lips and jaw, and the patient may note a rhythmic clicking of the teeth. In the limbs, the tremor usually is most distally in the fingers (pill rolling) or may manifest by flexion-extension or a supination-pronation, oscillatory movement of the wrist and forearm, and flexion-extension movement of the ankle. In severe forms, it may be present more proximally, causing the entire body to shake. The presence of head tremor (titubation) should raise the possibility of essential tremor or of dystonic tremor associated with cervical dystonia or cerebellar outflow tremor, as is seen in patients with MS or posterior fossa disorders rather than PD. Tremor in the legs, and especially in the feet while sitting, is usually caused by parkinsonian rest tremor. A history of progression from unilateral arm tremor to additional involvement of the ipsilateral leg suggests parkinsonism rather than essential tremor. Once the tremor has become noticeable to the patient, a variety of methods are used to conceal the movement, such as holding one hand with the other, sitting on the affected hand, or crossing the legs to dampen a tremulous lower limb. Many patients find that they can briefly abort the tremor by conscious effort.