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