The previous motor system chapters have deconstructed the motor system into its component parts, in an effort to portray how the brain’s “divide and conquer” strategy assigns different motor control tasks to different brain regions. This chapter describes the types of 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:
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:
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 extrapyramidal disorders. Dyskinesias
Akinesias
A number of well-known movement disorders are associated with basal ganglia dysfunction. We shall concentrate on 3 of the most well-understood: Parkinson’s disease, Huntington’s 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. Parkinson’s disease Parkinson’s 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 Parkinson’s disease is still not known, much has been learned in the past 15 years from the development of an animal model of Parkinson’s disease. This model was discovered by accident when a number of young patients presented with symptoms remarkably similar to Parkinson’s 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 Parkinson’s 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.
There is no cure for Parkinson’s disease, but a number of effective treatments exist. The earliest effective treatment was developed when it was first discovered that Parkinson’s 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 patient’s 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. Huntington’s disease Huntington’s 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 Huntington’s disease. It is an autosomal dominant mutation, such that the offspring of a patient with Huntington’s disease has a 50% chance of inheriting the mutation. Individuals with the mutated gene will invariably develop Huntington’s 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. Huntington’s disease is also known as Huntington’s 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 Huntington’s disease. Why does the loss of indirect pathway neurons in the striatum cause the dyskinesias of Huntington’s 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.
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.
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.
Test Your Knowledge
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
Following a strenuous workout with his neighborhood team, a right-handed, 52-year-old former professional basketball player awoke the next morning with paralysis of the right lower extremity. A neurological exam revealed an exaggerated stretch reflex. There was no disturbance of position sense, pain sensation or tactile discrimination. Where is the problem localized?
All of the following are examples of dyskinesia EXCEPT:
All of the following are examples of dyskinesia EXCEPT:
All of the following are examples of dyskinesia EXCEPT:
All of the following are examples of dyskinesia EXCEPT:
All of the following are examples of dyskinesia EXCEPT:
All of the following are examples of dyskinesia EXCEPT:
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