Hypokinesia Many patients with milder defects in their intentional ("when") systems may not demonstrate a total inability to initiate a response (e.g., akinesia); rather their intentional disorder may be primarily a delay in initiating a response. We have termed this delay hypokinesia. This hypokinesia may be defined in a manner similar to akinesia. Because a teaction time paradigm is required to detect hypokinesia, it can- not be divided into exo-evoked and endo-evoked subtypes. Hypokinesia can be seen both in the limbs and in the eyes and may be either independent of direction or directionally specific such that when making directional movements, there is a greater delay initiating movements in a contra- lesional direction than there is initiating movements in an ipsilesional direction. Hypokinesia can also be hemispatial such that movements with the same limb may be slower in one hemispace than they are in the other hemispace.

PARKINSONISM The initial feature of many basa! ganglia diseases is slowness of movement (bradykincsia) and paucity or absence of movement (akinesias), often associated with rigidity and ttemor (Jankovic 2003). Some authors have used the term hypokinesia to describe a reduction in amplitude of movement. Many parkinsonian symptoms are explained by the combination of slowness and poverty of movement and increase in muscle tone. The term parkin- sonism is used to describe a syndrome manifested by a combination of the following six cardinal features: (1) tremor at rest, (2) rigidity, (3) bradykincsia, (4) loss of postural reflexes, (5) flexed posture, and (6) freezing (motor blocks). A combination of these signs is used to clinically define definite, probable, and possible parkinsonism. Diagnosis of definite parkinsonism requires that at least two of these features must be present, with one of them being resting tremor or rigidity; probable parkinsonism consists of resting tremor or rigidity alone; and possible parkinsonism includes at least two of the remaining four features. The four major characteristics of parkinsonism tremor, rigidity, akinesia, and postural disturbances {form- ing the acronym TRAP)account for most of the clinical abnormalities described here. The most common cause of idiopathic parkinsonism (akinetic-rigid syndrome) is Parkinson's disease (PD). As a resulr of advances in genetics, many forms of idiopathic parkinsonism have been found to result from mutations in specific genes, such as those coding fot cc-synuclein or the Parkin protein. Whereas some of the gene mutations (e.g., a-synuclein gene) are very rare causes of parkinsonism, Parkin gene mutations account for up to 50% of all patients with early-onset parkinsonism. Because PD is defined as idiopathic parkinsonism, the notion of multiple Parkinson's diseases should be considered to draw atten- tion to the different genetic causes of idiopathic parkinson- ism, Besides genetic causes, there are many other causes of pure parkinsonism and of parkinsonism combined with other neurological deficits (parkinsonism-plus syndromes) (Table 24.1). 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 expres- sion (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 often is 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, often is misdiagnosed as bursitis, arthritis, or rotator cuff disorders. 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 pro- minent complaint, one must consider bulbar involvement in one of the parkinsonism-plus syndromes, such as progres- sive supranuclear palsy (PSP) and multiple system atrophy (MSA; Thomas and Jankovic 2003b; Table 24.2). Dressing tasks, such as fastening small buttons or getting arms into sleeves, often are difficult. Hygiene becomes impaired. As with most other tasks, disability is greater if the dominant arm is more affected (e.g., shaving, brushing teeth, and other repetitive movements usually arc affected the most). Speech becomes slurred and loses its volume (hypopho- nia), as a result of which patients are often asked to repeat themselves. A large number of additional speech distur- bances may occur, including stuttering and palilalia (involuntary repetition of a phrase with increasing rapid- ity). Early pronounced voice changes often indicate a diagnosis other than PD (e.g., palilalia is more commonly a feature of PSP and MSA). Another problem related to impairment of bulbar function is excessive salivation and drooling. Initially, this may occur only at night, but later it MOVEMENT DISORDERS: DIAGNOSIS AND ASSESSMFA I 29.S Tabic 24.1: Classification of parkinsonism 1. Primary (idiopathic) parkinsonism Parkinson's disease Juvenile parkinsonism II. Multisystem degenerations ("parkinsonism plus") Progressive supranuclear palsy Multiple system atrophy Striatonigral degeneration Olivopontocerebellar atrophy Shy-Drager syndrome Lytico-Bodig or parkinsonism-dementia-ALS complex of Guam Corticobasal degeneration Progressive pallidal atrophy Parkinsonism-demcnria complex Pallidopyramidal disease III. Heredodegencrative parkinsonism Hcreditaty juvenile dystonia-parkinsonism (autosomal recessive Parkin mutation) Do pa-responsive dystonia Autosomal dominant Lewy body disease Huntington's disease Wilson's disease Hereditary ceruloplasmin deficiency Pantothenate kinase associated neurodegencration, also known as ncurodegeneration with brain iron accumulation, and Hallervotden-Spatz disease Olivopontocerebellar and spinocerebellar atrophies including Macliado-Joseph disease Familial amyotrophy-dementia-parkinsonism Disinhibition-dementia-parkinsonism-amyotrophy complex G e rstma n n -Stra u ssle r- Sc h ei n ker d ise ase Familial progressive subcortical gliosis I.ubag (X-linked dystonia-parkinsonism) Familial basal ganglia calcification Mitochondrial cytopathies with striatal necrosis Ceroid lipofuscinosis Familial parkinsonism with peripheral neuropathy Parkinsonian-pyramidal syndrome Neuroacanthocytosis Hereditary hemochromatosis IV. Secondary (acquired, symptomatic) patkinsonism Infectious: postencephalitic, acquired immunodeficiency syndrome, subacute sclerosing panencephalitis, Crcutzfeldt-Jakob disease, prion diseases Drugs: dopamine receptor blocking drugs (antipsychotic, antiemetic drugs), rcscrpine, tetrabenazine, a-mcthyldopa, lithium, fhtnarizine, cinnarizine Toxins: MPTP, carbon monoxide, manganese, mercury, carbon disulfide, cyanide, methanol, ethanol Vascular: multi-infarct, Binswangcr's disease Trauma: pugilistic encephalopathy Other: parathyroid abnormalities, hypothyroidism, hepatocerebral degeneration, brain tumor, paraneoplastic, normal-pressure hydrocephalus, n onco m mu n ica ti ng h y d rocephaluSj sy ri ngomescneep ha I i a, hemiatrophy - h em i p a rk i nso nism, peripherally induced tremor and parkinsonism, and psychogenic Table 24.2: Park in son ism-pi us syndromes: differential diagnosis Brady kinesia Rigidity Gait disturbance Tremor Ataxia Dysautonomia Dementia Dysarthria or dysphagia Dystonia Eyelid apraxia Limb apraxia Motor neuron disease Myoclonus Neuropathy Oculomotor deficit Sleep impairment Asymmetrical findings l.-dopa response i.-dopa dyskinesia Family history Putaminal T2 hypo in tensity Lewy bodies PD + + + + - + - - - - - + + + - + rsr + + + - - + i + - - - - + - - - -SDS + + + - + _L - - - + - - - + SND + + + - - - + - - - - + OPCA + + F - 4- - - - - t- - - - + CBD - + - - - + + - - + - + - + - - - - DLB 1. - - -: - - - - - - - - - - + PDACG + 1 + + + + - - - - + - - + - - - - - - -CBD = corticobasal degeneration; DLB = dementia with Lewy bodies; OPCA = olivopontocerebellar atrophy (the cerebellar form of sporadic multiple system atrophy); I'D = Parkinson's disease; PDACG = parkinsonism-dementia-amyottophic lateral sclerosis complex of Guam; PSP = progressive supranuclear palsy; SDS = Shy-Drager syndrome; SND = sttiatonigral degeneration. Source: Modified from Jankovic, J. 1995b, "Treatment of parkinsonian syndromes," in Treatment of Movement Disorders, ed R. Kurlan, J.B. Lippincorr, Philadelphia, 95-114. 2% APPROACH TO COMMON NEUROLOCTCAL PROBLEMS 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 interpret these difficulties as resulting from "weakness." Generalized loss of energy and easy fatigability arc also common complaints. "Walking becomes slowed and shuffling, with flexion of the knees and narrow base. When involvement is asymmetrical, one leg may drag behind the other. Stride then becomes shortened, 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 to become 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 besides 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 (see Table 24.2). Dementia may be seen in a variety of parkinsonism syndromes (see Chapters 72 and 77), Depression also is a common problem, and patients often lose their assertiveness and become with- drawn, more passive, and less motivated to socialize. The term bradyphrenia has been used to describe the slowness of thought processes and inattentiveness that are often seen. Complaints related to autonomic dysfunction arc also common. In all parkinsonian syndromes, constipation is a common complaint and may become severe. However, fecal incontinence is not seen in PD unless the motor disability is such that the patient cannot maneuver to the bathroom or dementia is superimposed. Bladder com- plaints, such as frequency, nocturia, and the sensation of incomplete bladder emptying, may occur. A mild to moderate degree of orthostatic hypotension is common in parkinsonian disorders, and antiparkinsonian drugs often aggravate the problem (see Chapter 77). 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 77). Besides impotence with early loss of nocturnal or morning erections and inability to maintain erection during intercourse, the other symptom that may precede the onset of motor problems associated with MSA is a sleep disorder, such as sleep apnea or REM sleep behavior disorder, Visual complaints usually are not a prominent feature, with the following specific exceptions. In PD, diplopia may occur during reading secondary to impaired convergence. Other parkinsonian disorders, particularly PSP and the olivopontocerebellar atrophies, sometimes have visual complaints (see Chapter 78). Oculogyric crises, which are sudden episodes of involuntary ocular deviation (most often up and to the side) in the absence of neuroleptic drug exposure, arc virtually pathognomonic of parkinsonism after encephalitis lethargica, although they may be seen in rare neuromctabolic 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, which are sometimes quite disabling. Although a variety of neurophysiology] 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 PD Rating Scale (UPDRS), Hoehn-Yahr Stages, and Schwab-England Scale of activities of daily living (Table 24,3). The historical section of the UPDRS can be self-administered and reliably completed by nondemented patients. In some clinical research studies the UPDRS is supplemented by a more objective timed test such as the Purdue pegboard test and movement and reaction times. Many scales, such as the PD questionnaire 39 (PDQ-39) and the PD quality of life questionnaire (PDQL), attempt to assrss the overall qualm t lite. Onset and Course As in other movement disorders, the age of onset of a parkinsonian syndrome is clearly important in considering a differential diagnosis. Although the majority of patients arc adults, parkinsonism can be seen in childhood (see fable 24.1 j. I'D usually lias a slow onset and very gradual progression. Generally, patients with early-onset PD and those with tremor-dominant form tend to progress at a slower rate and arc less likely to have an associated cognitive decline than those with postural instability and the gait difficulty form of PD. Other disorders (such as those caused by toxins, cerebral anoxia, or infarction) may present abruptly or progress more rapidly (resulting in so- called malignant parkinsonism) and may even improve spontaneously (as in those caused by drugs, multiple infarcts, and certain forms of encephalitis). PLATE 24,1 Kayser-Fleischer ring. Note the golden-brown full- circumference ring thickest and most readily seen between the 11 o'clock and 1 o'clock positions of the cornea. -2.3