hapter 6: Disorders of the Motor System

James Knierim, Ph.D., Department of Neuroscience, The Johns Hopkins University

The previous motor system chapters have deconstructed the motor system into its
component parts, in an effort to portray how the brains divide and conquer
strategy assigns different motor control tasks to different brain regions. This chapter
describes
the types
of
Video of Clinical Correlate Lecture on Friedreich's Ataxia
disorders
that result from damage or disease to different parts of the motor system. In the
process, the different components of the motor system are reviewed to see how
they work together to produce the fluid, effortless body movements that we take for
granted. An emphasis is placed on trying to explain the causes and symptoms of
motor system disorders in terms of the basic principles of neuroanatomy and
neuronal function that you learned in the earlier chapters.

6.1 Lower Motor Neuron Syndrome

The first level of the motor system hierarchy is the spinal cord, the location of the
alpha motor neurons that constitute the final common pathway of all motor
commands. Alpha motor neurons directly innervate skeletal muscle, causing the
contractions that produce all movements. Reflex circuits and other circuitry within
the spinal cord underlie the automatic processing of many of the direct commands to
the muscles (the nuts and bolts processing), thereby freeing higher-order areas to
concentrate on more global, task-related processing.
Motor system dysfunction can result from damage or disease at any level of the
motor system hierarchy and side-loops. Differences in the symptoms that result
from damage at different levels allow the clinician to localize where in the hierarchy
the damage is likely to be. Damage to alpha motor neurons results in a
characteristic set of symptoms called the lower motor neuron syndrome (lower
motor neurons refer to alpha motor neurons in the spinal cord and brain stem; all
motor system neurons higher in the hierarchy are referred to as upper motor
neurons). This damage usually arises from certain diseases that selectively affect
alpha motor neurons (such as polio) or from localized lesions near the spinal cord.
Lower motor neuron syndrome is characterized by the following symptoms:
1. The effects can be limited to small groups of muscles. Recall that
a motor neuron pool is a nucleus of alpha motor neurons that innervate a
single muscle (link to Motor Unit Figure 2). Furthermore, nearby motor
neuron pools control nearby muscles. Thus, restricted damage to lower motor
neurons, either within the spinal cord or at the ventral roots, will affect only a
restricted group of muscles.

2. Muscle atrophy. When alpha motor neurons die, the muscle fibers that they
innervate become deprived of necessary trophic factors and eventually the
muscle itself atrophies.
3. Weakness. Because of the damage to alpha motor neurons and the atrophy
of muscles, weakness is profound in lower motor neuron disorders.
4. Fasciculation. Damaged alpha motor neurons can produce spontaneous
action potentials. These spikes cause the muscle fibers that are part of that
neurons motor unit to fire, resulting in a visible twitch (called a fasciculation)
of the affected muscle (Figure 6.1).

Figure 6.1
Fasciculatio
ns and
fibrillations.
Click on
buttons to
see
demonstrati
on.

5.
6. Fibrillation. With further degeneration of the alpha motor neuron, only
remnants of the axons near the muscle fibers remain. These individual axon
fibers can also generate spontaneous action potentials; however, these action
potentials will only cause individual muscle fibers to contract. This

spontaneous twitching of individual muscle fibers is called a fibrillation (Fig.

1). Fibrillations are too small to be seen as a visible muscle contraction. They
can only be detected with electrophysiological recordings of the muscle
activity (an electromyogram).
7. Hypotonia. Because alpha motor neurons are the only way to stimulate
extrafusal muscle fibers, the loss of these neurons causes a decrease in
muscle tone.
8. Hyporeflexia. The myotatic (stretch) reflex is weak or absent with lower
motor neuron disorders, because the alpha motor neurons that cause muscle
contraction are damaged.

6.2 Upper Motor Neuron Syndrome

Damage to any part of the motor system hierarchy above the level of alpha motor
neurons (not including the side loops) results in a set of symptoms termed
the upper motor neuron syndrome. Some of these symptoms are opposite of
those of lower motor neuron disorders. Thus, one of the critical determinations a
clinician must make is whether a patient presenting with motor problems has an
upper motor neuron disorder or a lower motor neuron disorder.
Upper motor neuron disorders typically arise from such causes as stroke, tumors,
and blunt trauma. For example, strokes to the middle cerebral artery, lateral striate
artery, or the medial striate artery can cause damage to the lateral surface of cortex
or to the internal capsule, where the descending axons of the corticospinal tract
collect. The symptoms of upper motor neuron syndrome are:
1. The effects extend to large groups of muscles. Recall from the Motor
Cortex chapter that muscles from different body parts are activated by
stimulation of parts of motor cortex, consistent with the notion that motor
cortex represents movements that are controlled by many joints, rather than
individual muscles. Thus, a stroke in a particular part of motor cortex will
affect the activation of many muscles in the body. Likewise, a stroke that
affects the internal capsule or crus cerebri could affect muscles on the entire
contralateral side of the body.
2. Atrophy is rare. Because alpha motor neurons are present, muscles will
continue to receive trophic agents necessary for their survival. A mild amount
of atrophy may result from disuse, but it will not be as pronounced as that
resulting from a lower motor neuron disorder.
3. Weakness. Upper motor neuron disorders produce a graded weakness of
movement (paresis), which differs from the complete loss of muscle activity
caused by paralysis (plegia).
4. Absence of fasciculations. Because alpha motor neurons themselves are
spared, fasciculations do not occur.
5. Absence of fibrillations. Likewise, fibrillations do not occur.
6. Hypertonia. Upper motor neuron disorders result in an increase in muscle
tone. Recall that descending motor pathways can modulate the intrinsic

circuitry that is present in the spinal cord. This modulatory input can be either
inhibitory or excitatory. Through mechanisms that are not well understood,
the loss of descending inputs tends to result in an increased firing rate of
alpha and/or gamma motor neurons. The higher firing rate causes an increase
in the resting level of muscle activity, resulting in hypertonia.
7. Hyperreflexia. Because of the loss of inhibitory modulation from descending
pathways, the myotatic (stretch) reflex is exaggerated in upper motor
neuron disorders. The stretch reflex is a major clinical diagnostic test of
whether a motor disorder is caused by damage to upper or lower motor
neurons.
8. Clonus. Sometimes the stretch reflex is so strong that the muscle contracts a
number of times in a 5-7 Hz oscillation when the muscle is rapidly stretched
and then held at a constant length. This abnormal oscillation, called clonus,
can be felt by the clinician.
9. Initial contralateral flaccid paralysis. In the initial stages after damage to
motor cortex, the contralateral side of the body shows a flaccid paralysis.
Gradually, over the course of a few weeks, motor function returns to the
contralateral side of the body. This gradual recovery of function results from
the ability of other motor pathways to take over some of the lost functions.
Recall that there are multiple descending motor pathways by which highorder information can reach the spinal cord. Thus, descending pathways such
as the rubrospinal and the reticulospinal tracts, which receive direct or
indirect cortical input, can take over the function lost by the damage to the
corticospinal tract. Moreover, primary motor cortex itself is capable of
reorganizing itself to recover some lost function. Thus, if the part of motor
cortex that controls a certain body movement is damaged, neighboring parts
of the motor cortex that are undamaged can, to some extent, alter their
function to help compensate for the damaged areas. The one major exception
to the recovery of function is that fine control of the distal musculature will
not be regained after a lesion to the corticospinal tract. Recall that there are
direct connections from primary motor cortex neurons to alpha motor neurons
controlling the fingers. These connections presumably underlie our abilities to
manipulate objects with great precision and to do such tasks as playing a
piano and performing microsurgery. None of the other descending pathways
have direct connections onto spinal motor neurons, and none of them can
compensate for the loss of fine motor control of the hands and fingers after
damage to the corticospinal tract.
10.Spasticity. A clinical sign of upper motor neuron disorder is a velocity
dependent resistance to passive movement of the limb. If the clinician moves
a patients limb slowly, there may be little resistance to the movement. As the
passive movement becomes quicker, however, at a certain point the muscle
will sharply resist the movement. This is referred to as a spastic catch. The
mechanism for this spasticity is not entirely known, but altered firing rate of
gamma motor neurons and their regulating interneurons may be involved, as
well as an increase in alpha motor neuron activity, causing an inappropriately
powerful stretch reflex to a fast stretch of the muscle. Sometimes, the
resistance becomes so great that the autogenic inhibition reflex is initiated,
causing a sudden drop in the resistance; this is referred to as the clasp-knife
reflex.

Figure 6.2
Babinski
sign.

11.Babinski sign. A classic neurological test for corticospinal tract damage is

the Babinski test. In this test, the clinician strokes the sole of the foot firmly
with an instrument. This elicits a normal plantar response in normal
individuals, as the toes curl inward. In patients with an upper motor neuron
disorder, however, an abnormal extensor plantar response is elicited, as the
big toe extends upward and the remaining toes fan out. This is called a
positive Babinski sign (Figure 6.2). Interestingly, the positive Babinski sign is
normal in infants for the first 2 years of life. During development, however,
the reflex changes to the normal adult pattern, presumably as corticospinal
circuits mature.
In addition to the above symptoms, damage to the motor cortex and association
cortex can result in impairments in motor planning and strategies and in an inability
to perform complex motor tasks. Performance of simple tasks is intact, but patients
are unable to perform complex, practiced tasks. This symptom is known as apraxia.
For example, patients may be unable to arrange a set of blocks to match an example
block-structure in front of them. They can move the blocks individually, but cannot
come up with a motor plan to arrange them properly. This disorder is known
as constructional apraxia. Other apraxias include dressing apraxia (inability to
dress oneself) and verbal apraxia (inability to coordinate mouth movements to
produce speech).

Paralysis
A section or crush of the spinal cord will result in paralysis of all parts of the body
below the damaged region. Even though such an injury occurs in the spinal cord, it
is not considered a lower motor neuron disorder, as the alpha motor neurons
themselves are not directly damaged. If the damage occurs at the cervical level,
then all four limbs will be paralyzed (quadriplegia). If the damage occurs below the
cervical enlargement, then only the legs are paralyzed (paraplegia). Other terms
used to describe patterns of paralysis are hemiplegia (paralysis to one side of the
body) and monoplegia (paralysis of a single limb).

6.3 Disorders of the Basal Ganglia

The basal ganglia have historically been considered part of the motor system
because of the variety of motor deficits that occur when they are damaged. The
types of symptoms that result from basal ganglia disorders can be divided into two
classes:dyskinesias, which are abnormal, involuntary movements, and akinesias,
which are abnormal, involuntary postures. Because the basal ganglia were once
considered to form a separate, extrapyramidal motor system, these symptoms are
called extrapyramidaldisorders.

Dyskinesias
1. Resting tremors are most often associated with Parkinsons disease.
When the patient is at rest, certain body parts will display a 4-7 Hz tremor.
For example, the thumb and forefingers will move back-and-forth against
each other in a characteristic tremor called pill-rolling tremor. The tremor
stops when the body part engages in active movement.
2. Athetosis is characterized by involuntary, writhing movements, especially of
the hands and face.
3. Chorea, which derives from the Greek word for dance, is characterized by
continuous, writhing movements of the entire body. It is viewed by some as
an extreme form of athetosis. Chorea is most closely identified
with Huntingtons disease.
4. Ballismus is characterized by involuntary, ballistic movements of the
extremities.
5. Tardive dyskinesia can result from the long-term use of antipsychotic drugs
that target the dopamine system. It is characterized by involuntary
movements of the tongue, face, arms, lips, and other body parts. It is
thought to occur as the result of an imbalance between the D1 and D2
receptors, thereby favoring the direct pathway over the indirect pathway.

Akinesias
1. Rigidity is a resistance to passive movement of the limb. Unlike spasticity,
rigidity does not depend on the speed of the passive movement. In some
patients, this resistance is so great that it is referred to as lead-pipe
rigidity, because moving the patients limb feels like bending a lead pipe. In
some patients, this rigidity is coupled with tremors and is
calledcogwheel rigidity, as moving the limb feels to the clinician like the
catching and release of gears. As with spasticity, the mechanism is not
entirely understood, but may result from continuous firing of alpha motor
neurons causing a continual contraction of the muscle.
2. Dystonia is the involuntary adoption of abnormal postures, as agonist and
antagonist muscles both contract and become so rigid that the patient cannot
maintain normal posture.
3. Bradykinesia refers to a slowness, or poverty, of movement.
A number of well-known movement disorders are associated with basal ganglia
dysfunction. We shall concentrate on 3 of the most well-understood: Parkinsons

disease, Huntingtons disease, and hemiballismus. To understand how these

disorders result in the specific symptoms, it is necessary to review the circuit
anatomy of the basal ganglia that was presented in the Basal Ganglia chapter.

Parkinsons disease
Parkinsons disease results from the death of dopaminergic neurons in
the substantia nigra pars compacta. It is characterized by a resting tremor, but the
most debilitating symptom is severe bradykinesia or akinesia. In advanced cases,
patients have difficulty initiating movements, although involuntary, reflexive
movements can be normal. It is as if the loss of the substantia nigra neurons has
put a brake on the output of motor cortex, inhibiting voluntary motor commands
from descending to the brain stem and spinal cord.
Although the cause of Parkinsons disease is still not known, much has been learned
in the past 15 years from the development of an animal model of Parkinsons
disease. This model was discovered by accident when a number of young patients
presented with symptoms remarkably similar to Parkinsons disease. These patients
were drug addicts who had been taking an artificially manufactured drug
called MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyradine). This drug destroyed
the dopaminergic neurons in the substantia nigra, leading to a Parkinsonian disorder.
Laboratory animals injected with MPTP have since become a leading model for
understanding the disease and developing treatments.
How does the loss of the dopaminergic neurons cause the poverty of movements
associated with Parkinsons disease (Figure 6.3)? Recall from the Basal Ganglia
chapter that the substantia nigra pars compacta projects to both direct pathway and
indirect pathways neurons in the striatum. Because there are two different types of
dopamine receptors, substantia nigra activity excites the direct pathway and inhibits
the indirect pathway. The net effect of the direct pathway is to excite motor cortex,
and the net effect of the indirect pathway is to inhibit motor cortex. Thus, the loss of
the nigrostriatal dopaminergic pathway upsets the fine balance of excitation and
inhibition in the basal ganglia and reduces the excitation of motor cortex. In ways
that are not understood, this reduction of thalamic excitation interferes with the
ability of the motor cortex to generate commands for voluntary movement, resulting
in the poverty of movement of Parkinsonian patients. It is as if all of the motor
programs stored in cortex are constantly inhibited by the indirect pathway, with not
enough excitation of the direct pathway for the desired motor program to become
activated.

Figure 6.3
Parkinsons
disease
results from
degeneratio
n of the
nigrostriatal
pathway.
Three
therapeutic
intervention
s are L-Dopa
therapy,
pallidotomy,
and deep
brain
stimulation.

There is no cure for Parkinsons disease, but a number of effective treatments exist.
The earliest effective treatment was developed when it was first discovered that
Parkinsons disease was caused by a loss of dopaminergic neurons. Because
dopamine itself does not cross the blood-brain barrier, L-Dopa, a chemical precursor
to dopamine, was used to replenish the supply of dopamine. Amazingly, flooding the
system with L-Dopa resulted in profound improvements in the symptoms of patients.
Unfortunately, this improvement is temporary, and typically symptoms return after a
number of years. Surgical intervention, such as making lesions to the globus pallidus
internal segment (pallidotomy), has shown effectiveness in some patients. In
recent years, a new therapy,deep brain stimulation of the subthalamic nucleus,
has been gaining in popularity. In this treatment, an electrical stimulator is
implanted in the subthalamic nucleus. When the electrical current is turned on to

stimulate the nucleus, the patients symptoms disappear immediately. It is not

known why this procedure works, or what its long-term efficacy is. Because the
projection from the subthalamic nucleus is excitatory onto globus pallidus neurons,
which inhibit the thalamus, it is paradoxical that such stimulation should increase
motor cortex activity. One thought is that the stimulation might actually overload the
subthalamic nucleus, thereby inhibiting it and disinhibiting the thalamus.

Huntingtons disease
Huntingtons disease (also known as Woody Guthrie Disease) is a genetic
disorder that is caused by an abnormally large number of repeats of the nucleotide
sequence CAG on chromosome 4. Normal individuals have 9-35 repeats of this
sequence; mutations that cause larger repeats give rise to Huntingtons disease. It is
an autosomal dominant mutation, such that the offspring of a patient with
Huntingtons disease has a 50% chance of inheriting the mutation. Individuals with
the mutated gene will invariably develop Huntingtons disease, usually near middle
age. The affected gene codes for a protein known as huntingtin, the function of
which is not known. The effect of the mutated version of the gene, however, is to kill
the indirect pathway neurons in the striatum, particularly those of the caudate
nucleus.
Huntingtons disease is also known as Huntingtons chorea because it is
characterized by a continuous, choreiform movements of the body (especially the
limbs and face). In addition, the disease in advanced stages is associated with
dementia. There is at present no cure or effective treatment for Huntingtons
disease.
Why does the loss of indirect pathway neurons in the striatum cause the dyskinesias
of Huntingtons disease (Figure 6.4)? Recall that the net effect of the indirect
pathway is to inhibit motor cortex. With the loss of these neurons, the excitatory
effect of the direct pathway is no longer kept in check by the inhibition of the
indirect pathway. Thus, the motor cortex gets too much excitatory input from the
thalamus, disrupting its normal functioning and sending involuntary movement
commands to the brain stem and spinal cord. Because inappropriate motor programs
are not inhibited normally, the cortex continuously sends involuntary commands for
movements and movement sequences to the muscles.

Figure 6.4
Huntington
s disease
results from
degeneratio
n of the
indirect
pathways
cells of the
striatum.

Hemiballismus
Hemiballismus results from a unilateral lesion to the subthalamic nucleus, usually
caused by a stroke. This lesion results in ballismus on the contralateral side of the
body, while the ipsilateral side is normal (hence the term hemiballismus). The
involuntary, ballistic movements result from the loss of the excitatory subthalamic
nucleus projection to the globus pallidus (Figure 6.5). Because the globus pallidus
internal segment normally inhibits the thalamus when excited, the loss of the
subthalamic component lessens the inhibition of the thalamus, making it more likely
to send spurious excitation to the motor cortex. Some surgical operations have been
performed to relieve the symptoms of hemiballismus, and new pharmacological
treatments are in use to relieve the disorder.

Figure 6.5
Hemiballism
us results
from
unilateral
damage to
the
subthalamic
nucleus.

6.4 Disorders of the Cerebellum

Like the basal ganglia, the cerebellum has historically been considered part of the
motor system because damage to it produces motor disturbances. Unlike the basal
ganglia, damage to the cerebellum does not result in lack of movement or poverty of
movement. Instead, cerebellar dysfunction is characterized by a lack of movement
coordination. Also unlike basal ganglia (and motor cortex), damage to the
cerebellum causes impairments on the ipsilateral side of the body.
1. Ataxia is a general term used to describe the general impairments in
movement coordination and accuracy that accompany cerebellar damage.
There are two major forms of cerebellar ataxia.
a. Disturbances of posture or gait result from lesions to
the vestibulocerebellum. Patients have difficulty maintaining posture
because of the loss of the fine-control mechanisms programmed by

cerebellar circuits that translate vestibular signals into precise, welltimed muscle contractions to counter small sways in the body. As a
result, patients often develop abnormal gait and stances to
compensate. For example, the feet are often spaced widely apart when
the patient stands still, as this provides a more stable base to maintain
balance. In addition, patients display a staggering gait, with a
tendency to fall toward the side of the lesion. This gait resembles that
of a drunken individual; indeed, alcohol is known to affect the firing of
Purkinje cells, which may explain the loss of coordination that
accompanies inebriation.
b. Decomposition of movement results from the loss of the
cerebellums ability to coordinate the activity and timing of many
muscle groups to produce smooth, fluid movements. Instead,
cerebellar patient decompose each movement into its component
parts, performing them in serial, rather than all at once in a
coordinated fashion.

Figure 6.6
Dysdiadocho
kinesia. A
normal
subject can
easily
perform
rhythmic
movements
like rapidly
pronating
and
supinating
the hands
and
forearms
(click
NORMAL). A
patient with
a cerebellum
lesion
cannot
perform this
task

2. Dysmetria refers to the inappropriate force and distance that characterizes

target-directed movements of cerebellar patients. For example, in attempting
to grab a cup, they may move their hand outward with too much force or may
move it too far, with the result of knocking over the cup instead of grabbing
it.
3. Dysdiadochokinesia refers to the inability of cerebellar patients to perform
rapidly alternating movements, such as rapidly pronating and supinating the
hands and forearms (Figure 6.6). This diagnostic sign results from the lack of
the cerebellums ability to coordinate the timing of muscle groups, alternately
contracting and inhibiting antagonistic muscles, to produce the rhythmic
movements.
4. Scanning speech refers to the often staccato nature of speech of cerebellar
patients. The production of speech is a motor act, as muscles of the jaw,
tongue, and larynx need to work in unison to produce words and sounds.
Cerebellar patients have difficulty in coordinating these muscle groups
appropriately, and therefore their speech tends to be slow and disjointed.
5. Hypotonia is another symptom of cerebellar damage. There is a decreased,
pendulous myotatic reflex, as the decreased muscle resistance tends to cause
the limb to swing back and forth after the initial reflex contraction.
6.

Figure 6.7

Intention
tremor. A
normal
subject can
make a
directed
movement
to a target
(click
NORMAL). A
patient with
a cerebellum
lesion
displays an
intention
tremor, in
which the
movement
starts
smoothly
toward the
target but
then
oscillates
back and
forth until
the hand
slowly
contacts the
target (click
ABNORMAL).

7. Intention tremor refers to the increasingly oscillatory trajectory of a

cerebellar patients limb in a target-directed movement (Figure 6.7). For
example, the hand will start out on a straight path toward the target, but as it
gets closer, the hand begins to move back and forth, and the patient must
slow down the movement and very carefully approach the target. Note that
this tremor contrasts with the resting tremor of Parkinsons disease, which
disappears when the movement is made. Intention tremor is absent when the
hand is still, but appears toward the end of a target-directed movement.
8. Nystagmus is an oscillatory movement of the eyes, resulting from damage
to the vestibulocerebellum. Recall that one function of the cerebellum is to
fine-tune the gain of the vestibuloocular response. Damage to the cerebellum
can disrupt this circuitry, resulting in a continuing oscillation of the eyes.
9. Delay in initiating movements. Cerebellar patients take longer to initiate
movements, often because they must actively plan sequences of movements
that are performed effortlessly by normal individuals.
10.In addition to movement disorders, cerebellar patients also demonstrate
subtle cognitive deficits, such as an impaired ability to estimate time
intervals.