Neurology_Adams

Neurology_Adams. The distribution of the paralysis caused by upper motor neuron (supranuclear) lesions varies with the locale of the lesion, but certain features are characteristic of all of them. A group of muscles is always involved, never individual muscles, and if any movement is possible, the proper relationships between agonists, antagonists, synergists, and fixators are preserved. On careful inspection, the paralysis never involves all the muscles on one side of the body, even in the severest forms of hemiplegia. Movements that are invariably bilateral—such as those of the eyes, jaw, pharynx, upper face, larynx, neck, thorax, diaphragm, and abdomen—are affected little or not at all. This occurs because these muscles are bilaterally innervated; that is, stimulation of either the right or left motor cortex results in contraction of these muscles on both sides of the body. Upper motor neuron paralysis is rarely complete for any long period of time; in this respect it differs from the absolute


Neurology_Adams

Neurology_Adams. cortex results in contraction of these muscles on both sides of the body. Upper motor neuron paralysis is rarely complete for any long period of time; in this respect it differs from the absolute paralysis that results from destruction of anterior horn cells or interruption of their axons.


Neurology_Adams

Neurology_Adams. Upper motor neuron lesions are characterized further by certain peculiarities of retained movement. There is decreased voluntary drive on spinal motor neurons (fewer motor units are recruitable and their firing rates are slower), resulting in a slowness of movement. There is also an increased degree of cocontraction of antagonistic muscles, reflected in a decreased rate of rapid alternating movements. These abnormalities probably account for the greater sense of effort and the manifest fatigability in effecting voluntary movement of the weakened muscles. Another phenomenon is the activation of paralyzed muscles as parts of certain automatisms (synkinesias). For example, the paralyzed arm may move suddenly during yawning and stretching. Attempts by the patient to move the hemiplegic limbs may also result in a variety of associated movements. Thus, flexion of the arm may result in involuntary pronation and flexion of the leg or in dorsiflexion and eversion of the foot. Also, volitional


Neurology_Adams

Neurology_Adams. may also result in a variety of associated movements. Thus, flexion of the arm may result in involuntary pronation and flexion of the leg or in dorsiflexion and eversion of the foot. Also, volitional movements of the paretic limb often evoke imitative (mirror) movements in the normal one or vice versa. Mirror movements are also a feature of Parkinson disease and of lesions in the upper cervical spinal cord. In some patients, as they recover from hemiplegia, a variety of movement abnormalities emerge, such as tremor, athetosis, and chorea on the affected side. These are expressions of damage to basal ganglionic and thalamic structures and are discussed in Chap. 4.


Neurology_Adams

Neurology_Adams. If the upper motor neurons are interrupted above the level of the facial nucleus in the pons, hand and arm muscles are affected most severely and the leg muscles to a lesser extent; of the cranial musculature, only muscles of the tongue and lower part of the face are involved to any significant degree (Fig. 3-5). Because Broadbent was the first to call attention to this distribution of facial paralysis that relatively spares the forehead muscles, it has been referred to as “Broadbent’s law.” The precise course taken by fibers that innervate the facial nucleus is still somewhat uncertain; however, the majority crosses in the mid-pons to innervate the contralateral facial nerve nucleus. Some fibers may descend to the upper medulla and then ascend recurrently to the pons (Pick’s bundle), accounting for the rare, mild facial weakness that may be seen with lesions of the lower pons and upper medulla.


Neurology_Adams

Neurology_Adams. At lower levels, such as the cervical cord, complete, acute, and bilateral lesions of the upper motor neurons not only cause a paralysis of voluntary movement but also temporarily abolish the spinal reflexes of segments below the lesion. This is the condition referred to earlier as spinal shock, a state of acute flaccid paralysis that is replaced later by spasticity. A comparable state of areflexia and hypotonia may occur with acute cerebral lesions but is less sharply defined than is the spinal state. With some acute cerebral lesions, spasticity and paralysis develop together; in others, especially with parietal lesions, the limbs remain flaccid but reflexes are retained. Spasticity, Hyperreflexia, and the Babinski Sign


Neurology_Adams

Neurology_Adams. Spasticity, Hyperreflexia, and the Babinski Sign The identifying characteristics of paralysis from an upper motor neuron lesion are a predilection for involvement of certain muscle groups, a specific pattern of response of muscles to passive stretch (where resistance increases linearly in relation to velocity of stretch), and a manifest exaggeration of tendon reflexes. The antigravity muscles—the flexors of the arms and the extensors of the legs—are predominantly affected. The arm tends to assume a flexed and pronated position and the leg an extended and adducted one, indicating that certain spinal neurons are reflexly more active than others.


Neurology_Adams

Neurology_Adams. At rest, with the muscles shortened to midposition, they are flaccid to palpation and electromyographically silent. If the arm is extended or the leg flexed very slowly, there may be little or no change in muscle tone. By contrast, if the muscles are briskly stretched, the limb moves freely for a very short distance (free interval), beyond which there is an abrupt catch and then a rapidly increasing muscular resistance up to a point; then, as passive extension of the arm or flexion of the leg continues, the resistance melts away. This velocity-dependent tone constitutes the “clasp-knife” phenomenon of spasticity. With the limb in the extended or flexed position, a new passive movement may not encounter the same sequence. Thus, the essential feature of spasticity is a velocity-dependent increase in the resistance of muscles to a passive stretch stimulus. Although a clasp-knife relaxation following peak resistance is highly characteristic of cerebral hemiplegia, it is by no means found


Neurology_Adams

Neurology_Adams. in the resistance of muscles to a passive stretch stimulus. Although a clasp-knife relaxation following peak resistance is highly characteristic of cerebral hemiplegia, it is by no means found consistently. At times, a form of velocity-independent hypertonia is found that is termed rigidity and is more characteristic of basal ganglia lesions as discussed in Chap. 4.


Neurology_Adams

Neurology_Adams. Clinicians have known for some time that there is not a constant relationship between spasticity and weakness. Severe weakness may be associated with only the mildest signs of spasticity; in contrast, the most extreme degrees of spasticity, observed in certain patients with cervical spinal cord disease, may seem disproportionate to the extent of weakness, signifying that these two states depend on separate mechanisms. Indeed, the selective blocking of small gamma neurons abolishes spasticity as well as hyperactive segmental tendon reflexes but leaves power unchanged.


Neurology_Adams

Neurology_Adams. The heightened stretch reflexes (tendon jerks) of the spastic state may be a “release” phenomenon—the result of interruption of descending inhibitory pathways. Animal experiments have demonstrated that this aspect of the spastic state is mediated through disinhibition of spindle efferents (increased tonic activity of gamma motor neurons) and through loss of the influence of reticulospinal and vestibulospinal pathways that act on alpha motor neurons. The clasp-knife phenomenon appears to derive at least partly from a lesion (or presumably a change in central control) of a specific portion of the reticulospinal system.


Neurology_Adams

Neurology_Adams. The pathophysiology of spasticity is further dependent on two more refined descending tracts: (1) the dorsal reticulospinal tract, which has inhibitory effects on stretch reflexes; and (2) the medial reticulospinal and vestibulospinal tracts, which together facilitate extensor tone. In cerebral and capsular lesions, cortical inhibition from these pathways is reduced, resulting in spastic hemiplegia. In spinal cord lesions that involve the corticospinal tract, the dorsal reticulospinal tract is usually involved as well. If the latter tract is spared, only paresis, loss of support reflexes, and possibly release of flexor reflexes (Babinski phenomenon) occur. In some instances, flaccidity persists after hemiplegic stroke, possibly as a result of primary involvement of the lenticular nucleus of the basal ganglia and the thalamus as suggested by Pantano and colleagues.


Neurology_Adams

Neurology_Adams. The most reliable indications of an upper motor neuron lesion are the signs described by Babinski in 1896 (the great toe sign) and 1903 (the toe abduction, or fan sign) (Fig. 3-6). In modern parlance, the toe and fan signs have generally been conflated and termed the Babinski sign. Numerous monographs and articles have been written about the sign: a comprehensive one, by van Gijn, and an elegant but more arcane one by Fulton and Keller. A worthwhile biography of Babinsk has been written by Phillipon and Poirer.


Neurology_Adams

Neurology_Adams. In its essential form, the sign consists of extension of the large toe and extension and fanning of the other toes during and immediately after stroking the lateral plantar surface of the foot. The stimulus is applied along the dorsum of the foot from the lateral heel and sweeping upward and across the ball of the foot. The stimulus must be firm but not necessarily painful. Several dozen surrogate responses (with numerous eponyms) have been described over the years, most utilizing alternative sites and types of stimulation, but all have the same significance as the Babinski response.


Neurology_Adams

Neurology_Adams. As Babinski himself indicated, a movement resembling the Babinski sign is present in normal infants (see Phiilipon and Poirer), but it disappears and its persistence or emergence in late infancy and childhood or later in life is an invariable indicator of a lesion at some level of the corticospinal tract. There has been considerable discussion regarding the form and meaning of the sign in infants, some surveys such as the one by Hogan and Milligan indicating that the first movement of the great toe is flexor, others, that the four toes fan outward but do not extend and that the sign differs from the one in adults. To some extent, the nature of the stimulus is responsible for variation in the response.


Neurology_Adams

Neurology_Adams. Clinical and electrophysiologic observations indicate that the extension movement of the great toe is a component of a larger synergistic flexion or shortening reflex of the leg—that is, toe extension when viewed from a physiologic perspective is a protective (nocifensive, or defensive) response. The most characteristic of these is the “triple flexion response,” in which the hip, thigh, and ankle flex (dorsiflex) slowly, following an appropriate stimulus. These spinal flexion reflexes, of which the Babinski sign is the most characteristic, are common accompaniments to—but not essential components of—spasticity. They are present because of disinhibition or release of motor programs of spinal origin. Important characteristics of these responses are their capacity to be induced by weak superficial stimuli (such as a series of pinpricks) and their tendency to persist for a few moments after the stimulation ceases. With incomplete suprasegmental lesions, the response may be fractionated;


Neurology_Adams

Neurology_Adams. stimuli (such as a series of pinpricks) and their tendency to persist for a few moments after the stimulation ceases. With incomplete suprasegmental lesions, the response may be fractionated; for example, the hip and knee may flex but the foot may not dorsiflex, or vice versa.


Neurology_Adams

Neurology_Adams. The hyperreflexic state that characterizes spasticity may take the form of clonus, a series of rhythmic involuntary muscular contractions occurring at a frequency of 5 to 7 Hz in response to an abruptly applied and sustained stretch stimulus. It is usually designated in terms of the part of the limb to which the stimulus is applied (e.g., patella, ankle). The frequency is constant within 1 Hz and is not appreciably modified by altering peripheral or central nervous system activities. Clonus requires an appropriate degree of muscle relaxation, integrity of the spinal stretch reflex mechanisms, sustained hyperexcitability of alpha and gamma motor neurons (suprasegmental effects), and synchronization of the contraction–relaxation cycle of muscle spindles.


Neurology_Adams

Neurology_Adams. The cutaneomuscular abdominal and cremasteric reflexes (“cutaneous, or superficial reflexes”) are elicited by rapid, gentle stroking of the skin overlying these muscles, and are usually abolished when the upper motor neuron is damaged acutely. They are difficult to interpret because they are absent in some normal individuals and may disappear after acute spinal injury, only to reappear at a later time.


Neurology_Adams

Neurology_Adams. Spread, or radiation of reflexes, is regularly associated with spasticity, although it may be observed to a slight degree in normal persons with brisk tendon reflexes. Tapping of the radial periosteum, for example, may elicit a reflex contraction not only of the brachioradialis but also of the biceps, triceps, or finger flexors. This spread of reflex activity is probably not the result of radiation of impulses in the spinal cord, but a result of the propagation of a vibration wave from bone to muscle, stimulating the excitable muscle spindles in its path (Lance). Other manifestations of the hyperreflexic state are the Hoffmann sign and the crossed adductor reflex of the thigh muscles. Also, reflexes may be “inverted,” as in the case of a lesion of the fifth or sixth cervical segment. Here the biceps and brachioradialis reflexes are abolished and in response to a tap over the distal radius or the biceps tendon, only the remaining triceps and finger flexor reflex arcs are engaged.


Neurology_Adams

Neurology_Adams. With bilateral cerebral lesions, exaggerated stretch reflexes may be elicited in cranial as well as limb and trunk muscles because of interruption of the corticobulbar pathways. These are seen as easily triggered masseter contractions in response to a brisk downward tap on the chin (“jaw jerk”) and brisk contractions of the orbicularis oris muscles in response to tapping the philtrum or corners of the mouth. In advanced cases, weakness or paralysis or slowness of voluntary movements of the face, tongue, larynx, and pharynx are added (bulbar spasticity or “pseudobulbar” palsy; see also Chap. 24).


Neurology_Adams

Neurology_Adams. The many investigations of the biochemical changes that underlie spasticity and the mechanisms of action of antispasticity drugs have been reviewed by Davidoff. Because glutamic acid is the neurotransmitter of the corticospinal tracts, one would expect its action on inhibitory interneurons to be lost. As mentioned earlier, GABA and glycine are the major inhibitory transmitters in the spinal cord; GABA functions as a presynaptic inhibitor, suppressing sensory signals from muscle and cutaneous receptors. Baclofen, a derivative of GABA, is thought to act by reducing the release of excitatory transmitters from the presynaptic terminals of primary afferent terminals. Diazepam and other benzodiazepines have a similar effect but by a different mechanism of potentiating postsynaptic GABA receptors. Actually, none of these agents is entirely satisfactory in the treatment of spasticity when administered orally; the administration of baclofen intrathecally at times has a more beneficial effect.


Neurology_Adams

Neurology_Adams. Actually, none of these agents is entirely satisfactory in the treatment of spasticity when administered orally; the administration of baclofen intrathecally at times has a more beneficial effect. The antispasticity agent tizanidine acts by yet another mechanism as an alpha-2 adrenergic agonist, which increases presynaptic inhibition. Glycine is the transmitter released by inhibitory interneurons and is measurably reduced in quantity, uptake, and turnover in the spastic animal. There is some evidence that the oral administration of glycine reduces experimentally induced spasticity. Interruption of descending noradrenergic, dopaminergic, and serotonergic fibers is undoubtedly involved in the genesis of spasticity, although the exact mode of action of these neurotransmitters on the various components of spinal reflex arcs remains to be defined.


Neurology_Adams

Neurology_Adams. Table 3-1 summarizes the main attributes of upper motor neuron lesions and contrasts them with those of the lower motor neuron discussed above. Motor Disturbances Caused by Lesions of the Parietal Lobe


Neurology_Adams

Neurology_Adams. Motor Disturbances Caused by Lesions of the Parietal Lobe As indicated earlier in this section, a significant portion of the pyramidal tract originates in neurons of the parietal cortex. Also, the parietal lobes are important sources of visual and tactile information necessary for the control of movement. Pause and colleagues have described the motor disturbances caused by lesions of the parietal cortex. The patient is unable to maintain stable postures of the outstretched hand when his eyes are closed and cannot exert a steady contraction. Exploratory movements and manipulation of small objects are impaired, and the speed of tapping is diminished. Posterior parietal lesions (involving areas 5 and 7 in Fig. 3-3) are more detrimental in this respect than anterior ones (areas 1, 3, and 5), but both regions are affected in patients with the most severe deficits.


Neurology_Adams

Neurology_Adams. All that has been said about the cortical and spinal control of the motor system gives one only a limited idea of human motility. Viewed objectively, the conscious and sentient human organism is continuously active—fidgeting, adjusting posture and position, sitting, standing, walking, running, speaking, manipulating tools, or performing the intricate sequences of movements involved in athletic or musical skills. Some of these activities are relatively simple, automatic, and stereotyped. Others have been learned and mastered through intense conscious effort and with long practice have become habitual—that is, reduced to an automatic level—a process not at all understood physiologically. Still others are complex and voluntary, parts of a carefully formulated plan, and demand continuous attention and thought. What is more remarkable, one can be occupied in several of these variably conscious and habitual activities simultaneously, such as driving through heavy traffic while dialing a


Neurology_Adams

Neurology_Adams. and thought. What is more remarkable, one can be occupied in several of these variably conscious and habitual activities simultaneously, such as driving through heavy traffic while dialing a cellular phone (not endorsed) and engaging in animated conversation. Moreover, when an obstacle prevents a particular sequence of movements from accomplishing its goal, a new sequence can be undertaken automatically for the same purpose.


Neurology_Adams

Neurology_Adams. The term apraxia denotes a disorder in which an attentive patient loses the ability to execute previously learned activities in the absence of weakness, ataxia, sensory loss, or extrapyramidal derangement that would be adequate to explain the deficit. All the elements of the activity may be demonstrated in circumstances other than in response to the command to execute the activity or gesture. This was the meaning given to apraxia by Liepmann, who introduced the term in 1900, and discussed further by Denny-Brown in 1958.


Neurology_Adams

Neurology_Adams. Any explanation of apraxia requires an appreciation of the interplay between cortical areas that create highly complex motor behaviors. On the basis of studies of patients with lesions of different parts of the brain, it appears that the initiating and assembling of the complex motor activities and continuously modifying the components of a motor sequence are directed by the frontal lobes. Lesions of the frontal lobes have the effect of impeding the organization of motor sequences in the contralateral limbs so that a complex activity will not be initiated or sustained long enough to permit its completion, or it may be performed awkwardly. However, clinical and functional imaging data indicate that planned or commanded action is formulated not in the frontal lobe, where the impulse to action arises, but in the parietal lobe of the language-dominant hemisphere, where visual, auditory, and somesthetic information is integrated. The formation of ensembles of skilled movements, which


Neurology_Adams

Neurology_Adams. action arises, but in the parietal lobe of the language-dominant hemisphere, where visual, auditory, and somesthetic information is integrated. The formation of ensembles of skilled movements, which Liepmann called a “space-time plan,” depends on the integrity of the dominant parietal lobe; if this part of the brain is damaged, complex patterns of movement cannot be activated at all or the movements are awkward and inappropriate.


Neurology_Adams

Neurology_Adams. Apraxia has been traditionally divided into three types: ideational, ideomotor, and limb-kinetic. They are described in greater detail in Chap. 21 but a brief account is provided here because of their intimate involvement with motor activity. The failure to conceive or formulate an action to command was referred to by Liepmann as ideational apraxia. Sensory areas 5 and 7 in the dominant parietal lobe, the supplementary and premotor cortices of both cerebral hemispheres and their integral connections are involved collectively to accomplish these actions. In ideomotor apraxia, the patient may know and remember the planned action, but because these areas or their connections are interrupted, he cannot actually execute it with either hand. Certain tasks are said to differentiate ideomotor from ideational apraxia, as discussed further on, but the distinction may be quite subtle. Nonetheless, ideational apraxia has been said to be characterized by difficulty in “what to do,” whereas


Neurology_Adams

Neurology_Adams. from ideational apraxia, as discussed further on, but the distinction may be quite subtle. Nonetheless, ideational apraxia has been said to be characterized by difficulty in “what to do,” whereas ideomotor apraxia is a block in “how to do” as a result of an inability to transmit the gesture to executive motor centers.


Neurology_Adams

Neurology_Adams. A third disorder, opaque to many neurologists, is limb-kinetic apraxia (or kinetic-limb apraxia). It is a clumsiness and maladroitness that is the result of an inability to fluidly connect or to isolate individual movements of the hand and arm as described by Kleist. In the originally conceived form, a hand displays awkwardness that is disproportionate to weakness or sensory loss, yet gestures and complex movements can be accomplished, unlike the case in ideomotor apraxia. Central to the disorder is a breakdown of fine fractionated finger movements for which reason the nature of limb kinetic apraxia and its differentiation from a mild corticospinal disorder has been elusive enough that many neurologists do not view it as a true apraxia.


Neurology_Adams

Neurology_Adams. The term limb-kinetic apraxia has also been applied to cases of paralysis that obscures the apraxia on one side but causes a breakdown of fine finger movements on the opposite side. This is more properly termed “sympathetic apraxia.” In particular, in a right-handed person, a lesion in the left frontal lobe that includes Broca’s area, the left motor cortex, and the deep underlying white matter may cause left-limb apraxia. Clinically, there is a nonfluent aphasia, a right hemiparesis, and clumsiness of the nonparalyzed left hand.


Neurology_Adams

Neurology_Adams. These high-order abnormalities of learned movement patterns have several unique features. Seldom are they evident to the patient himself and therefore they are not sources of complaint, even if they disrupt daily activities such as dressing. Or, if the patient appreciates them, he has difficulty describing the problem except in narrow terms of the activity that is impaired, such as using a phone or dressing. For this reason they are also often overlooked by the examining physician. Obviously, if the patient is confused or aphasic, spoken or written requests to perform an act will not be understood and one must find ways of persuading him to imitate the movements of the examiner. Moreover, the patient must be able to recognize and name the articles that he attempts to manipulate.


Neurology_Adams

Neurology_Adams. In practical terms, as mentioned, the lesion responsible for ideomotor apraxia, which affects both hands, usually resides in the left parietal region. Kertesz and colleagues provided evidence that the lesions responsible for aphasia and apraxia are different, although the two conditions are frequently associated because of their origin in the left hemisphere. The exact location of the parietal lesion, whether in the supramarginal gyrus or in the superior parietal lobe (areas 5 and 7) and whether subcortical or cortical, has been variable.


Neurology_Adams

Neurology_Adams. Although the majority of ideational and ideomotor apraxias occur with lesions in the left cerebral hemisphere, the right hemisphere retains some of these capacities. A small number of apraxic patients have right hemisphere damage. This also explains the preservation of most praxis skills in the left hand following callosal lesions. Geschwind accepted Liepmann’s proposition that a lesion of a subcortical tract (presumably the arcuate fasciculus) can disconnect the parietal from the left frontal cortex, accounting for the ideomotor apraxia of the right limbs. The apraxia in the left limb is the consequence of a functional disconnection of the left and right premotor association cortices. These conceptualizations, while possibly valid, are of more theoretic than practical significance and depend heavily on the disconnection model discussed in Chap. 21. An alternative view is that there is not an actual disconnection of the two frontal lobes as much as there is a failure of the left to


Neurology_Adams

Neurology_Adams. depend heavily on the disconnection model discussed in Chap. 21. An alternative view is that there is not an actual disconnection of the two frontal lobes as much as there is a failure of the left to activate the right frontal lobe because the right does not receive instructions from the damaged left parietal lobe. It is the dominant parietal lobe that still embodies the property of praxis.


Neurology_Adams

Neurology_Adams. Of a somewhat different nature is an oral-buccal-lingual apraxia, which is probably the most commonly observed of all apraxias in practice. It may occur with lesions that undercut the left supramarginal gyrus or the left motor association cortex and may or may not be associated with the apraxia of the limbs described above. Such patients are unable to carry out facial movements on command (lick the lips, blow out a match, etc.), although they may do better when asked to imitate the examiner or when confronted with a lighted match. With lesions that are restricted to the facial area of the left motor cortex, the apraxia will be limited to the facial musculature bilaterally and may be associated with a verbal apraxia or cortical dysarthria (namely, Broca’s aphasia, see Chap. 22). The so-called apraxia of gait is considered in


Neurology_Adams

Neurology_Adams. The so-called apraxia of gait is considered in Chap. 6, but strictly speaking, this is not an apraxia since walking is not truly a learned act. The terms dressing apraxia and constructional apraxia are used to describe special manifestations of nondominant parietal lobe disease, in contrast to the above-described forms of apraxia that result from lesions on the dominant side. Although dressing apraxia in many ways resembles an ideomotor apraxia, it probably has a basis in a form of a loss of appreciation of extrapersonal space. These issues are discussed further in Chap. 21.


Neurology_Adams

Neurology_Adams. Testing for apraxia is carried out in several ways. First, one observes the actions of the patient as he engages in simulated tasks as dressing, washing, shaving, and using eating utensils. Second, the patient is asked to carry out familiar symbolic acts—wave goodbye, salute the flag, shake a fist as though angry, or blow a kiss. If he fails, he is asked to imitate such acts made by the examiner. Finally, he is asked to show how he would hammer a nail, brush his teeth, take a comb out of his pocket and comb his hair, or to execute a more complex act, such as lighting and smoking a cigarette or opening a bottle of soda, pouring some into a glass, and drinking it. These latter actions, involving more complex sequences, are said to be tests of ideational apraxia; the simpler and familiar acts are considered tests of ideomotor apraxia. To perform these tasks in the absence of the tool or utensil is always more demanding because the patient must mentally formulate a plan of action rather


Neurology_Adams

Neurology_Adams. are considered tests of ideomotor apraxia. To perform these tasks in the absence of the tool or utensil is always more demanding because the patient must mentally formulate a plan of action rather than engage in a habitual motor sequence. The patient may fail to carry out a commanded or suggested activity (e.g., to take a pen out of his pocket), yet a few minutes later he may perform the same motor sequence automatically.


Neurology_Adams

Neurology_Adams. Children with various cerebral diseases that delay development are often unable to learn the sequences of movement required in hopping, jumping over a barrier, hitting or kicking a ball, or dancing. They suffer a developmental motor apraxia. This leads to a form of physical awkwardness that may be seen in the developmentally delayed child. Certain tests quantitate failure in these age-linked motor skills (see Chap. 27).


Neurology_Adams

Neurology_Adams. In the authors’ opinion, the time-honored division of apraxia into ideational, ideomotor, and kinetic types is not entirely satisfactory because of the difficulty separating them in practice. We have sometimes been unable to confidently separate ideomotor from ideational apraxia. The patient with a severe ideomotor apraxia nearly always has difficulty at the ideational level and, in any case, similarly situated left parietal lesions give rise to both types. Furthermore, in view of the complexity of the motor system, we have frequently been uncertain whether the clumsiness or ineptitude of a hand in performing a motor skill represents a kinetic apraxia or some other subtle fault in hand control by the corticospinal or one of the other parallel motor systems.


Neurology_Adams

Neurology_Adams. A related but poorly understood disorder of movement has been termed the alien hand. In the absence of volition, the hand and arm undertake complex and seemingly purposeful movements such as reaching into a pocket or handbag, placing the hand behind the head, tugging on the opposite hand or other body part, and rebuttoning the shirt immediately after it has been unbuttoned by the other hand. These activities may occur even during sleep. The patient is aware of the movements but has the sense that the actions are beyond his control and there is often an impression that the hand is estranged, as if commanded by an external agent (although the limb is recognized as one’s own—there is no anosognosia); a grasp reflex and a tendency to grope are usually present. Most instances arise as a result of infarction in the territory of the opposite anterior cerebral artery, including the corpus callosum. When the callosum is involved, Feinberg and colleagues find that there frequently appears to be


Neurology_Adams

Neurology_Adams. of infarction in the territory of the opposite anterior cerebral artery, including the corpus callosum. When the callosum is involved, Feinberg and colleagues find that there frequently appears to be a conflict between the actions of the hands, the normal one sometimes even restraining the alien one. Damage in the left supplementary motor area from any cause, as well as from the degenerative parietal lobe disease called corticobasal ganglionic degeneration are associated with a similar alien hand syndrome. A third form that results from a stroke in the posterior cerebral artery territory with associated sensory loss has also been observed by Ay and colleagues.


Neurology_Adams

Neurology_Adams. Finally, the complexity of motor activity is almost beyond imagination. Reference was made earlier to the reciprocal innervation involved in an act as simple as making a fist. Scratching one’s shoulder has been estimated to recruit about 75 muscles. But what must be involved in playing a piano concerto? Over a century ago Hughlings Jackson commented that “There are, we shall say, over thirty muscles in the hand; these are represented in the nervous centers in thousands of different combinations, that is, as very many movements; it is just as many chords, musical expressions, and tunes can be made out of a few notes.” The execution of these complex movements, many of them learned and habitual, is made possible by the cooperative activities of not just the motor and sensory cortices but integrally of the basal ganglia, cerebellum, and reticular formation of the brainstem. All are continuously integrated and controlled by feedback mechanisms from the sensory and spinal motor neurons.


Neurology_Adams

Neurology_Adams. integrally of the basal ganglia, cerebellum, and reticular formation of the brainstem. All are continuously integrated and controlled by feedback mechanisms from the sensory and spinal motor neurons. These points, already touched upon in this chapter, are elaborated in the following three chapters.


Neurology_Adams

Neurology_Adams. A historical perspective that outlines the development of these concepts is given by Faglioni and Basso and an authoritative review of the subject of apraxia can be found in the chapter by Heilman and Gonzalez-Rothi. The diagnostic considerations in cases of paralysis can be simplified by using the following subdivision, based on the location and distribution of the muscle weakness: 1. Monoplegia refers to weakness or paralysis of all the muscles of one leg or arm. This term is not applied to paralysis of isolated muscles or groups of muscles supplied by a single nerve or motor root. 2. Hemiplegia, the commonest form of paralysis, involves the arm, the leg, and sometimes the face on one side of the body. With rare exceptions, mentioned further on, hemiplegia is attributable to a lesion of the corticospinal system on the side opposite to the paralysis. 3.


Neurology_Adams

Neurology_Adams. 3. Paraplegia indicates weakness or paralysis of both legs. It is most often the result of diseases of the thoracic spinal cord, cauda equina, or peripheral nerves, and rarely, both medial frontal cortices. 4. Quadriplegia (tetraplegia) denotes weakness or paralysis of all four extremities. It may result from disease of the peripheral nerves, muscles, or myoneural junctions; gray matter of the spinal cord; or the upper motor neurons bilaterally in the cervical cord, brainstem, or cerebrum. Diplegia is a special form of quadriplegia in which the legs are affected more than the arms. Triplegia occurs most often as a transitional condition in the development of, or partial recovery from, tetraplegia. 5. Isolated paralysis of one or more muscle groups due to disease of muscle, anterior horn cells, or nerve roots. 6. Nonparalytic disorders of movement (e.g., apraxia, ataxia, rigidity). 7. Hysterical paralysis.


Neurology_Adams

Neurology_Adams. 6. Nonparalytic disorders of movement (e.g., apraxia, ataxia, rigidity). 7. Hysterical paralysis. The examination of patients who complain of weakness of one limb often discloses an asymptomatic weakness of another, and the condition is actually a hemiparesis or paraparesis. Or, instead of weakness of most of the muscles in a limb, only isolated groups are found to be affected. Ataxia, sensory disturbances, or reluctance to move the limb because of pain should not be misinterpreted as weakness. Parkinsonism may give rise to the same error, as can other causes of rigidity or bradykinesia or a mechanical limitation resulting from arthritis and bursitis. The presence or absence of atrophy of muscles in a monoplegic limb is of particular diagnostic help, as indicated below.


Neurology_Adams

Neurology_Adams. This is most often caused by a lesion of the cerebral cortex or the spinal cord (where it causes a monoplegia of the leg). Infrequently monoplegia or fragments of it result from a restricted subcortical lesion that interrupts the motor pathways to one limb. A cerebral vascular lesion is the most common cause; a circumscribed tumor or abscess may have the same effect. Small cortical lesions in the motor strip may rarely be so selective as to cause restricted regions of weakness, for example, of parts of the hand. Multiple sclerosis and spinal cord tumor, early in their course, may cause weakness of one limb, usually the leg. Monoplegia caused by a lesion of the upper motor neuron is usually accompanied by spasticity, increased reflexes, and an extensor plantar reflex (Babinski sign). In acute diseases of the lower motor neurons, the tendon reflexes are reduced or abolished, but atrophy may not appear for several weeks. Monoplegia with Muscular Atrophy


Neurology_Adams

Neurology_Adams. Monoplegia with Muscular Atrophy This is more frequent than monoplegia without muscular atrophy. Long-continued disuse of one limb may lead to atrophy, but it is usually of lesser degree than atrophy caused by lower motor neuron disease (denervation atrophy). In disuse atrophy, the tendon reflexes are retained and nerve conduction studies are normal. With denervation of muscles, there may be visible fasciculations and reduced or abolished tendon reflexes in addition to paralysis. The location of the lesion (in nerves, spinal roots, or spinal cord) can usually be determined by the pattern of weakness, by the associated neurologic symptoms and signs, and by special tests—MRI of the spine, examination of the cerebrospinal fluid (CSF), and electrical studies of nerve and muscle. If the limb is partially denervated, the EMG shows reduced numbers of motor unit potentials (often of large size) as well as fasciculations and fibrillations.


Neurology_Adams

Neurology_Adams. A complete atrophic brachial monoplegia is uncommon; more often, only parts of a limb are affected. When present in an infant, it suggests brachial plexus trauma from birth; in a child, poliomyelitis or other viral infection of the spinal cord; and in an adult, syringomyelia, amyotrophic lateral sclerosis, or a brachial plexus lesion. Atrophic crural (leg) monoplegia is more frequent than atrophic brachial monoplegia and may be caused by any lesion of the lumbosacral spinal cord or plexus. The mode of onset and temporal course differentiate the various diseases that affect these structures. A prolapsed intervertebral disc and several varieties of mononeuropathy almost never paralyze all or most of the muscles of a limb.


Neurology_Adams

Neurology_Adams. This is the most frequent form of paralysis. With rare exceptions this pattern of paralysis is a result of involvement of the corticospinal pathways. The site or level of the lesion—that is, cerebral cortex, corona radiata, capsule, brainstem, or spinal cord—can usually be deduced from the associated neurologic findings. Diseases localized to the cerebral cortex, cerebral white matter (corona radiata), and internal capsule usually manifest themselves by weakness or paralysis of the leg, arm, and lower face on the opposite side. The occurrence of seizures or the presence of a language disorder (aphasia), a loss of discriminative sensation (e.g., astereognosis, impairment of tactile localization), anosognosia, or a homonymous visual field defect suggests a contralateral cortical or subcortical location rather than at a lower level.


Neurology_Adams

Neurology_Adams. Damage to the corticospinal and corticobulbar tracts in the upper portion of the brainstem also causes paralysis of the face, arm, and leg of the opposite side (see Fig. 3-2). The lesion in the brainstem may be localized by the presence of a cranial nerve palsy or other segmental abnormality on the same side as the lesion (opposite the hemiplegia). These “crossed paralyses” are characteristic of brainstem lesions. With midbrain lesions there is a third nerve palsy (Weber syndrome); in low pontine lesions, an ipsilateral abducens or facial palsy is combined with a contralateral weakness or paralysis of the arm and leg (Millard-Gubler syndrome). Lesions in the medulla affect the tongue and sometimes the pharynx and larynx on one side and the arm and leg on the other. Even lower in the medulla, a unilateral infarct in the pyramid causes a flaccid paralysis of the contralateral arm and leg, with sparing of the face and tongue. The crossed brainstem syndromes are further described in


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Neurology_Adams. medulla, a unilateral infarct in the pyramid causes a flaccid paralysis of the contralateral arm and leg, with sparing of the face and tongue. The crossed brainstem syndromes are further described in Chaps. 33 and 44.


Neurology_Adams

Neurology_Adams. In some cases, an ipsilateral hemiplegia may be caused by a lesion in the corticospinal tract of the cervical spinal cord. In the spinal cord, however, the pathologic process is more often large and induces bilateral signs. A hemiparesis that spares the face, if combined with a loss of vibratory and position sense on the same side and a contralateral loss of pain and temperature, signifies disease of the spinal cord on the side of the hemiparesis (Brown-Séquard syndrome, as discussed in Chap. 42). As indicated above, in general there is little or no muscle atrophy following upper motor neuron lesions, as there is in diseases of the lower motor neuron. The atrophy in the former case is mainly a consequence of disuse.


Neurology_Adams

Neurology_Adams. When the motor cortex and adjacent parts of the parietal lobe are damaged in infancy or childhood, normal development of the muscles, as well as the skeletal system in the affected limbs, may be impaired. The limbs and even the trunk are smaller on one side than on the other. This does not happen if the paralysis occurs after puberty, by which time the greater part of skeletal growth has been attained. In hemiplegia caused by spinal cord lesions, muscles at the level of the lesion may atrophy as a result of damage to anterior horn cells or ventral roots.


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Neurology_Adams. In the causation of hemiplegia, ischemic and hemorrhagic vascular diseases of the cerebrum and brainstem exceed all others in frequency. Trauma (brain contusion, epidural and subdural hemorrhage) ranks second. Other important causes, less acute in onset, are, in order of frequency, brain tumor, demyelinating disease, brain abscess, and the vascular complications of meningitis and encephalitis. Most of these diseases can be recognized by their mode of evolution and characteristic imaging, which are presented in the chapters on specific neurologic diseases. Alternating transitory hemiparesis may be the result of a special type of migraine (see discussion in Chap. 9). Hysteria (conversion disorder) is another common cause of hemiplegia, as discussed further on.


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Neurology_Adams. Paralysis of both lower extremities may occur with diseases of the spinal cord, nerve roots, or, less often, the peripheral nerves. If the onset is acute, it may be difficult to distinguish spinal paralysis, which results in flaccidity and abolition of reflexes from spinal shock, from that due to peripheral nerve disease. In acute spinal cord diseases with involvement of corticospinal tracts, the paralysis or weakness affects all muscles below a given level; if the white matter is extensively damaged, sensory loss below a circumferential level on the trunk is conjoined (loss of pain and temperature sense because of spinothalamic tract damage, and loss of vibratory and position sense from posterior column involvement). Also in bilateral disease of the spinal cord, the bladder and bowel and their sphincters are usually affected. These abnormalities may be the result of an intrinsic lesion of the cord or an extrinsic mass that narrows the spinal canal and compresses the cord.


Neurology_Adams

Neurology_Adams. In peripheral nerve diseases, motor loss tends to involve the distal muscles of the legs more than the proximal ones (exceptions are certain varieties of the Guillain-Barré syndrome and some types of diabetic neuropathy and porphyria); sphincteric function is usually spared or impaired only transiently. Sensory loss, if present, is also more prominent in the distal segments of the limbs, and the degree of loss is often more for one modality than another. For clinical purposes, it is helpful to separate the acute paraplegias from the chronic ones and to divide the latter into two groups: those beginning in adult life and those occurring in infancy.


Neurology_Adams

Neurology_Adams. For clinical purposes, it is helpful to separate the acute paraplegias from the chronic ones and to divide the latter into two groups: those beginning in adult life and those occurring in infancy. The most common cause of acute paraplegia (or quadriplegia if the cervical cord is involved) is spinal cord trauma, usually associated with fracture–dislocation of the spine. Less common causes are a vascular malformation or fistula of the cord or its overlying dura, which causes ischemia by a complex mechanism, and infarction of the cord resulting from occlusion of the anterior spinal artery or, more often, from occlusion of segmental branches of the aorta as a feature of dissecting aneurysm or atheroma, vasculitis, or nucleus pulposus embolism. Epidural or subdural hemorrhage from a hemorrhagic diathesis or warfarin therapy causes an acute or subacute paraplegia; in a few instances the bleeding follows a lumbar puncture.


Neurology_Adams

Neurology_Adams. Paraplegia or quadriplegia that develops more slowly, subacutely over a period of hours or days is caused by postinfectious myelitis, demyelinating or necrotizing myelopathy, or epidural abscess or tumor with spinal cord compression. Paralytic poliomyelitis and acute Guillain-Barré syndrome—the former a purely motor disorder with mild meningitis, the latter predominantly motor but often with sensory disturbances—must be distinguished from the acute and subacute myelopathies and from each other.


Neurology_Adams

Neurology_Adams. In adult life, multiple sclerosis and tumor account for most cases of chronic spinal paraplegia, but a wide variety of extrinsic and intrinsic processes may produce the same effect: protruded cervical disc and cervical spondylosis (often with a congenitally narrow canal), epidural abscess and other infections (tuberculous, fungal, and other granulomatous diseases, HIV and HTLV-1), syphilitic meningomyelitis, motor system disease, subacute combined degeneration (vitamin B12 deficiency and copper deficiency), syringomyelia, epidural lipomatosis, neuromyelitis optica, and degenerative disease of the lateral and posterior columns. (See Chap. 42 for discussion of these spinal cord diseases.)


Neurology_Adams

Neurology_Adams. In pediatric practice, delay in starting to walk and difficulty in walking are common problems. These conditions may indicate a systemic disease (such as rickets), mental retardation, or, more commonly, a muscular or neurologic process. Congenital cerebral disease because of periventricular leukomalacia accounts for a majority of cases of infantile diplegia (weakness predominantly of the legs, with minimal weakness of the arms). Present at birth, it becomes manifest in the first months of life and may appear to progress, but actually the progression is only apparent, being exposed as the motor system develops; later there may seem to be slow improvement as a result of the normal maturation processes of childhood. These disorders fall under the heading of cerebral palsy, as discussed in Chap. 38. Congenital malformation or birth injuries of the spinal cord are other possibilities. Friedreich ataxia and familial paraplegia, muscular dystrophy, tumor, and the chronic varieties of


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Neurology_Adams. in Chap. 38. Congenital malformation or birth injuries of the spinal cord are other possibilities. Friedreich ataxia and familial paraplegia, muscular dystrophy, tumor, and the chronic varieties of polyneuropathy tend to appear later, during childhood and adolescence, and are slowly progressive causes of leg weakness and walking disorder. Transverse (usually demyelinative) myelitis is another cause of acute paraplegia in childhood.


Neurology_Adams

Neurology_Adams. All that has been said about the spinal causes of paraplegia applies to quadriplegia, the lesion being in the cervical rather than the thoracic or lumbar segments of the spinal cord. If the lesion is situated in the low cervical segments and involves the anterior half of the spinal cord, as typified by the syndrome resulting from occlusion of the anterior spinal artery, there is a level on the trunk, below which pinprick and thermal sense is lost but there is retained vibration, deep sensation, and joint position sense (anterior spinal artery syndrome). In all these processes, the paralysis of the arms may be flaccid and areflexic in type and that of the legs, spastic. If there is pain, it is usually in the neck and shoulders and there is numbness of the hands; elements of ataxia from posterior column lesions may accompany the paraparesis. Compression of the C1 and C2 spinal cord segments is caused by dislocation of the odontoid process. Rheumatoid arthritis and Morquio disease are


Neurology_Adams

Neurology_Adams. column lesions may accompany the paraparesis. Compression of the C1 and C2 spinal cord segments is caused by dislocation of the odontoid process. Rheumatoid arthritis and Morquio disease are other causes of compression of the upper cervical cord of special note; in the latter, there is pronounced dural thickening.


Neurology_Adams

Neurology_Adams. A progressive syndrome of monoparesis, biparesis, usually of the arms, and then triparesis involving the leg on the side of the last affected arm (“around the clock” pattern) is caused by tumors and a variety of other compressive lesions in the region of the foramen magnum and high cervical cord. This is putatively explained by the pattern of corticospinal fiber decussation at the cervico-medullary junction. Bilateral infarction of the medullary pyramids from occlusion of the vertebral arteries or their anterior spinal branches is a rare cause of quadriplegia. Repeated strokes affecting both hemispheres may lead to bilateral hemiplegia, usually accompanied by pseudobulbar palsy (see Chap. 22 on spastic dysarthria and


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Neurology_Adams. Chap. 24 on pseudobulbar laughing and crying). In infants and young children, aside from developmental abnormalities and anoxia of birth, certain metabolic cerebral diseases (metachromatic and other forms of leukoencephalopathy, lipid storage disease) may be responsible for a quadriparesis or quadriplegia, but always with psychomotor compromise. A rare pattern that may be considered a fragment of quadriplegia occurs in instances of infarction of the motor cortex in the vascular border zones between the middle and anterior cerebral arteries. The syndrome is one of paralysis of the proximal arms and sometimes, legs, colorfully called “man in the barrel.”


Neurology_Adams

Neurology_Adams. Paralysis that remains confined to three limbs is observed only rarely; more often the fourth limb is weak or hyperreflexic, and the syndrome is really an incomplete tetraplegia. As indicated earlier, this pattern of involvement is important, because it may signify an evolving lesion of the upper cervical cord or cervicomedullary junction. A meningioma of the foramen magnum, for example, may begin with spastic weakness of one limb, followed by sequential involvement of the other limbs in the above noted “around-the-clock” pattern. There are usually bilateral Babinski signs early in the process, but there may be few sensory findings. We have also seen this pattern in patients with multiple sclerosis and other intrinsic inflammatory and neoplastic lesions. These same diseases may produce triplegia (or triparesis) by a combination of paraplegia from a thoracic spinal cord lesion and a separate unilateral lesion in the cervical cord or higher that results in a hemiparesis.


Neurology_Adams

Neurology_Adams. Paralysis of Isolated Muscle Groups This pattern usually indicates a lesion of one or more peripheral nerves or of several adjacent spinal roots. The diagnosis of an individual peripheral nerve lesion is made on the basis of weakness or paralysis of a particular muscle or group of muscles and impairment or loss of sensation in the distribution of the nerve. Complete or extensive interruption of a peripheral nerve is followed by atrophy of the muscles it innervates and by loss of tendon reflexes of the involved muscles; abnormalities of vasomotor and sudomotor functions and trophic changes in the skin, nails, and subcutaneous tissue may occur if the condition has been chronic.


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Neurology_Adams. Detailed knowledge of the motor and sensory innervation of the peripheral nerve in question is needed for a diagnosis. It is impractical to memorize the precise sensorimotor distribution of each peripheral nerve and special manuals, such as Aids to the Examination of the Peripheral Nervous System, should be consulted (see also Table 43-1). Electromyography and nerve conduction studies are of great value for localization and to determine if the axon has been damaged or the process affects mainly myelin. If there is no evidence of upper or lower motor neuron disease but certain movements are nonetheless imperfectly performed, one should look for a disorder of position sense or cerebellar coordination or for rigidity with abnormalities of posture and movement due to disease of the basal ganglia (Chap. 4). In the absence of these disorders, the possibility of an apraxic disorder should be investigated by the methods outlined earlier. Psychogenic (Hysterical, Conversion)


Neurology_Adams

Neurology_Adams. Psychogenic paralysis may involve one arm or leg, both legs, or all of one side of the body. Tendon reflexes are of normal amplitude, there is no Babinski sign, and atrophy is lacking, features that distinguish it from chronic lower motor neuron disease. Diagnostic difficulty arises only in certain acute cases of upper motor neuron disease that lack the usual changes in reflexes and muscle tone. Sometimes there is loss of sensation in the paralyzed parts and loss of sight, hearing, and smell on the paralyzed side—a pattern of sensory changes that cannot be explained on the basis of organic disease of the nervous system. When the hysterical patient is asked to move the affected limbs, the movements tend to be slow, hesitant, and jerky, often with contraction of agonist and antagonist muscles simultaneously and intermittently (“give-way” weakness). Lack of effort is usually obvious, despite facial and other expressions to the contrary. Power of contraction improves with encouragement


Neurology_Adams

Neurology_Adams. simultaneously and intermittently (“give-way” weakness). Lack of effort is usually obvious, despite facial and other expressions to the contrary. Power of contraction improves with encouragement and the weakness is inconsistent; some movements are performed tentatively and moments later another movement involving the same muscles is performed naturally.


Neurology_Adams

Neurology_Adams. The Hoover sign and the trunk–thigh sign of Babinski are helpful in distinguishing hysterical from organic hemiplegia. The Hoover test is undertaken in the recumbent patient and is based on the downward pressure of one leg that is required to forcefully lift the opposite one. By placing the examiner’s hand under the heel of the unaffected leg, the sign is elicited when there is an absence of downward pressure as the patient attempts to raise the weak leg, thereby indicating a lack of voluntary effort. A second version of this test, also attributed to Hoover, is to detect downward pressure from the ostensibly paralyzed leg, as the good leg is raised. In a similar maneuver, the examiner tells the patient that he is testing the normal limb, while asking the patient to try to push the knees together. In hysterical weakness, the paralyzed limb adducts with normal power. One can take advantage of midline motor actions in the upper extremity by asking the patient to push his hands together


Neurology_Adams

Neurology_Adams. together. In hysterical weakness, the paralyzed limb adducts with normal power. One can take advantage of midline motor actions in the upper extremity by asking the patient to push his hands together and telling him that the normal side is being tested. In hysterical weakness, there is adduction movement of the supposedly paralyzed limb.


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Neurology_Adams. To carry out the Babinski trunk–thigh test, the examiner asks the recumbent patient to sit up while keeping his arms crossed in front of his chest. In the patient with organic hemiplegia from an upper motor neuron lesion, there is an involuntary flexion of the paretic lower limb; in organic paraplegia, both limbs are flexed as the trunk is flexed. In contrast, in hysterical hemiplegia, only the normal leg may be flexed; and in hysterical paraplegia, neither leg is flexed. Patients with apparently paralyzed legs who are seated in a rolling chair may propel themselves by pedaling along the floor (a sign attributed to Blocq by Okun and colleagues).


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Neurology_Adams. A discussion of motor paralysis would be incomplete without some reference to diseases in which muscle weakness may be profound but there are no overt structural changes in motor nerve cells or nerve fibers. Almost any disease of the neuromuscular junction and many diseases of muscle cause this combination. This group comprises myasthenia gravis, inflammatory myopathies, the muscular dystrophies, myotonia congenita (Thomsen disease), familial periodic paralysis, disorders of potassium, sodium, calcium, and magnesium metabolism, botulism, black widow spider bite, stiff-man syndrome, and the thyroid and other endocrine myopathies. In these diseases, each with a fairly distinctive clinical picture, the abnormality is essentially physiological or biochemical; their investigation requires EMG, special biochemical and histochemical tests, and electron microscopic study. These subjects are discussed in the sections on muscle disease later in this book.


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Neurology_Adams. Aids to the Examination of the Peripheral Nervous System. London, BallièreTindall/Saunders, 1986. Asanuma H: Cerebral cortical control of movement. Physiologist 16:143, 1973. Asanuma H: The pyramidal tract. In: Brooks VB (ed): Handbook of Physiology. Sec 1: The Nervous System. Vol 2: Motor Control, Part 2. Bethesda, MD, American Physiological Society, 1981, pp 702–733. Ay H, Buonanno FS, Price BH, et al: Sensory alien hand syndrome. J Neurol Neurosurg Psychiatry 65:366, 1998. Babinski J: De l’abduction des orteils (signe l’éventail). Rev Neurol 10:782, 1903. Babinski J: Sur le réflexe cutané plaintaire dans certains affections organiques deusysteme nerveux cebtral. Rev Neurol 4:415, 1896. Brodal P: The Central Nervous System: Structure and Function, 5th ed. New York, Oxford University Press, 1992. Bucy PC, Keplinger JE, Siqueira EB: Destruction of the pyramidal tract in man. J Neurosurg 21:285, 1964.


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Neurology_Adams. Bucy PC, Keplinger JE, Siqueira EB: Destruction of the pyramidal tract in man. J Neurosurg 21:285, 1964. Burke D, Lance JW: Myotatic unit and its disorders. In: Asbury AK, McKhann GM, McDonald WI (eds): Diseases of the Nervous System: Clinical Neurobiology, 2nd ed. Philadelphia, Saunders, 1992, pp 270–284. Davidoff RA: Antispasticity drugs: Mechanisms of action. Ann Neurol 17:107, 1985. Davidoff RA: Skeletal muscle tone and the misunderstood stretch reflex. Neurology 42:951, 1992. Denny-Brown D: The Cerebral Control of Movement. Springfield, IL, Charles C Thomas, 1966. Denny-Brown D: The nature of apraxia. J NervMent Dis 12:9, 1958. Evarts EV, Shinoda Y, Wise SP: Neurophysiological Approaches to Higher Brain Functions. New York, Wiley, 1984. Faglioni PR, Basso A: Historical perspectives on neuroanatomical correlates of limb apraxia. In: Roy EA (ed): Neuropsychological Studies of Apraxia and Related Disorders. Amsterdam, North Holland, 1985, pp 3–44.


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Neurology_Adams. Feinberg TE, Schindler RJ, Flanagan NG, Haber LD: Two alien hand syndromes. Neurology 42:19, 1992. Fulton JF: Physiology of the Nervous System. New York, Oxford University Press, 1938, Chap 20. Fulton JF, Keller AD: The Sign of Babinski. A Study in the Evolution of Cortical Dominance in Primates. Charles C Thomas, Springfield, 1932. Geschwind N: The apraxias: Neural mechanisms of disorders of learned movement. Am Sci 63:188, 1975. Gilman S, Marco LA: Effects of medullary pyramidotomy in the monkey. Brain 94:495, 515, 1971. Hallett M, Shahani BT, Young RR: EMG analysis of stereotyped voluntary movements in man. J Neurol Neurosurg Psychiatry 38:1154, 1975. Heilman KM, Gonzalez-Rothi LJ: Apraxia. In: Heilman KM, Valenstein E (eds): Clinical Neuropsychology, 4th ed. New York, Oxford University Press, 2003, pp 215–235. Heilman KM, Vlanestein E: Clinical Neuropsychology, 4th ed. Oxford, Oxford University Press, 2003.


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Neurology_Adams. Heilman KM, Vlanestein E: Clinical Neuropsychology, 4th ed. Oxford, Oxford University Press, 2003. Henneman E: Organization of the spinal cord and its reflexes. In: Mountcastle VB (ed): Medical Physiology, 14th ed. Vol 1. St. Louis, Mosby, 1980, pp 762–786. Hogan G, Milligan JE: The plantar reflex of the newborn. N Engl J Med 285:502, 1971. Iwatsubo T, Kuzuhara S, Kanemitsu A, et al: Corticofugal projections to the motor nuclei of the brain stem and spinal cord in humans. Neurology 40:309, 1990. Kertesz A, Ferro JM, Shewan CM: Apraxia and aphasia: The functional anatomical basis for their dissociation. Neurology 34:40, 1984. Kleist K: Leitunsgaphasie (Nachtsprechaphasie). In: Bonhoffer K (ed): Handbuch der artzilichen Erhahrungen im Welktriege. 1914/1918. Barth, Leipzig, 1934, pp 725–737. Lance JW: The control of muscle tone, reflexes and movement: Robert Wartenberg Lecture. Neurology 30:1303, 1980.


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Neurology_Adams. Lance JW: The control of muscle tone, reflexes and movement: Robert Wartenberg Lecture. Neurology 30:1303, 1980. Laplane D, Talairach J, Meininger V, et al: Motor consequences of motor area ablations in man. J Neurol Sci 31:29, 1977. Lassek AM: The Pyramidal Tract. Springfield, IL, Charles C Thomas, 1954. Lawrence DG, Kuypers HGJM: The functional organization of the motor system in the monkey. Brain 91:1, 15, 1968. Liepmann H: Das Krankheitsbild der Apraxie (motorische Asymbolie auf Grund eines Falles von einseitiger Apraxie). Monatsschr Psychiatr Neurol 8:15, 102, 182, 1900. Lorente de Nó R: Cerebral cortex: Architecture, intracortical connections, motor projections, in Fulton JF (ed): Physiology of the Nervous System, 3rd ed. New York, Oxford University Press, 1949, pp 288–330. Marx JJ, Ianetti GD, Thöme F, et al: Somatotopic organization of the corticospinal tract in the human brainstem: A MRI-based mapping analysis. Ann Neurol 57:824, 2005.


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Neurology_Adams. Marx JJ, Ianetti GD, Thöme F, et al: Somatotopic organization of the corticospinal tract in the human brainstem: A MRI-based mapping analysis. Ann Neurol 57:824, 2005. Mountcastle VB: Central nervous mechanisms in sensation. In: Mountcastle VB (ed): Medical Physiology, 14th ed. Vol 1: Part 5. St. Louis, Mosby, 1980, pp 327–605. Nathan PW, Smith M, Deacon P: Vestibulospinal, reticulospinal and descending propriospinal nerve fibers in man. Brain 119:1809, 1996. Nyberg-Hansen R, Rinvik E: Some comments on the pyramidal tract with special reference to its individual variations in man. Acta Neurol Scand 39:1, 1963. Okun MS, Rodriquez RL, Foote KD, et al: The “chair test” to aid in the diagnosis of psychogenic gait disorders. The Neurologist 13:87, 2007. Pantano P, Formisano R, Ricci M, et al: Prolonged muscular flaccidity after stroke. Morphological and functional brain alterations. Brain 118:1329, 1995.


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Neurology_Adams. Pantano P, Formisano R, Ricci M, et al: Prolonged muscular flaccidity after stroke. Morphological and functional brain alterations. Brain 118:1329, 1995. Pause M, Kunesch F, Binkofski F, Freund H-J: Sensorimotor disturbances in patients with lesions of the parietal cortex. Brain 112:1599, 1989. Phillipon J, Porier J: Joseph Babinski: A biography. New York, Oxford University Press, 2009, p 221. Roland PE: Organization of motor control by the normal human brain. Hum Neurobiol 2:205, 1984. Russell JR, DeMyer W: The quantitative cortical origin of pyramidal axons of Macaca rhesus, with some remarks on the slow rate of axolysis. Neurology 11:96, 1961. Terakawa H, Abe K, Nakamura M, et al: Ipsilateral hemiparesis after putaminal hemorrhage due to uncrossed pyramidal tract. Neurology 54:1801, 2000. Terao S, Miura N, Takeda A, et al: Course and distribution of facial corticobulbar tract fibers in the lower brainstem. J Neurol Neurosurg Psychiatry 69:262, 2000.


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Neurology_Adams. Terao S, Miura N, Takeda A, et al: Course and distribution of facial corticobulbar tract fibers in the lower brainstem. J Neurol Neurosurg Psychiatry 69:262, 2000. Thach WT Jr, Montgomery EB Jr: Motor system. In: Pearlman AL, Collins RC (eds): Neurobiology of Disease. New York, Oxford University Press, 1990, pp 168–196. Tower SS: Pyramidal lesion in the monkey. Brain 63:36, 1940. Van Gijn J: The Babinski Sign. A Centenarary. Universitiet Utrecht. Utrecht, 1996. Vulliemoz S, Raineteau O, Jabaudon D. Reaching beyond the midline: Why are human brains cross wired? Lancet Neurol 4:87, 2005.


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Neurology_Adams. Figure 3-1. A. Patellar tendon reflex. Sensory fibers of the femoral nerve (spinal segments L2 and L3) mediate this myotatic reflex. The principal receptors are the muscle spindles, which respond to brisk stretching of the muscle affected by tapping the patellar tendon. Afferent fibers from muscle spindles are shown entering only the L3 spinal segment, while afferent fibers from the Golgi tendon organ are shown entering only the L2 spinal segment. In this monosynaptic reflex, afferent fibers entering spinal segments L2 and L3 and efferent fibers issuing from the anterior horn cells of these and lower levels complete the reflex arc. Motor fibers show leaving the S2 spinal segment and passing to the hamstring muscles demonstrate the disynaptic pathway by which inhibitory influences are exerted upon an antagonistic muscle group during the reflex. B. The gamma loop is illustrated. Gamma efferent fibers (γ) pass to the polar portions of the muscle spindle. Contractions of the intrafusal


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Neurology_Adams. upon an antagonistic muscle group during the reflex. B. The gamma loop is illustrated. Gamma efferent fibers (γ) pass to the polar portions of the muscle spindle. Contractions of the intrafusal fibers in the polar parts of the spindle stretch the nuclear bag region and thus cause an afferent impulse to be conducted centrally. The afferent fibers from the spindle synapse with many alpha motor neurons. Because the alpha motor neurons innervate extrafusal muscle fibers, excitation of the alpha motor neurons by spindle afferents causes a cocontraction of the muscle. In this way, both gamma and alpha fibers can simultaneously activate muscle contraction. Both alpha and gamma motor neurons are influenced by descending fiber systems from supraspinal levels. (Adapted by permission from Carpenter MB, Sutin J: Human Neuroanatomy, 8th ed. Baltimore, Williams & Wilkins, 1983.)


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Neurology_Adams. Posterior limb of internal capsuleUpper limbEye fieldFaceMOTORCORTEXLower limbGenu of internal capsuleV N. motor nucleusVII N. nucleusXII N. nucleusVI N. nucleusCerebral peduncleMIDBRAINPONSMEDULLAMotor decussationMotor neurons for upper limbCrossed lateralcorticospinal tractPyramidUncrossed lateral corticospinal fibersVentral corticospinal tractMotor neurons for lower limbCERVICAL ENLARGEMENTLUMBOSACRAL ENLARGEMENT Figure 3-2. Corticospinal and corticobulbar tracts. The various lines indicate the trajectories of these pathways, from their origin in particular parts of the cerebral cortex to their nuclei of termination. 1Numbered areas in this and subsequent chapters refer to Brodmann areas of the cerebral cortex that are discussed in Chap. 22. “Layers” refer to the six neuronal layers of the cerebral cortex, also shown in detail in Chap. 22, on Cerebral Localization.


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Neurology_Adams. Figure 3-3. Lateral (A) and medial (B) surfaces of the human cerebral hemispheres, showing the areas of excitable cortex, numbered according to the scheme of Brodmann. (Reprinted with permission from House EL, Pansky B: A Functional Approach to Neuroanatomy, 2nd ed. New York, McGraw-Hill, 1967.) See also Fig. 22-1. Figure 3-4. The representation of body parts in the motor cortex, commonly called the motor homunculus. The large area of cortex devoted to motor control of the hand, lips, and face is evident. A in the smaller diagram represents the motor cortex; B is the sensory cortex. Figure 3-5. A. Supranuclear facial palsy. There is lower facial weakness contralateral to the lesion, but the upper face is spared due to its bilateral cortical innervation. B. Nuclear and infranuclear facial palsy. Both upper and lower portions of the face are weak.


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Neurology_Adams. Figure 3-6. A. The plantar response is elicited by stroking from the heel to the ball of the foot. B. The normal plantar response consists of flexion of the toes. C. The extensor plantar response (Babinski sign) consists of extension of the great toe coupled with fanning of the remaining digits. Disorders of Movement and Posture In this chapter, disorders of the automatic, static, postural, and other less-modifiable motor activities of the nervous system are discussed. Many of them are an expression of what has come to be called the extrapyramidal motor system, meaning—according to S.A.K. Wilson, who introduced this term—the motor structures of the basal ganglia and certain related thalamic and brainstem nuclei. However, others such as myoclonus and various tremors have obscure or multiple causes. These are discussed together because they are often combined and because of their inclusion in the clinical specialty of movement disorders.


Neurology_Adams

Neurology_Adams. The activities of the basal ganglia and the cerebellum are blended with and modulate the corticospinal system and the postural influence of the extrapyramidal system is indispensable to voluntary corticospinal movements. This close association of the basal ganglia and corticospinal systems becomes evident in the course of many forms of neurologic disease. In many aberrant motor patterns, one sees evidence not only of the activity of the basal ganglia but also of labyrinthine, tonic neck, and other postural reflexes that are mediated through nonpyramidal brainstem motor systems, including the vestibulospinal, rubrospinal, and reticulospinal tracts. Observations such as these have blurred the original distinctions between pyramidal and extrapyramidal motor systems. Nevertheless, this division remains a useful concept in clinical work because it informs a distinction among several motor syndromes—one that is characterized by a loss of volitional movement accompanied by spasticity—the


Neurology_Adams

Neurology_Adams. remains a useful concept in clinical work because it informs a distinction among several motor syndromes—one that is characterized by a loss of volitional movement accompanied by spasticity—the corticospinal syndrome; a second by bradykinesia, rigidity, and tremor without loss of voluntary movement—the hypokinetic basal ganglionic syndrome; a third by involuntary movements (choreoathetosis and dystonia)—the hyperkinetic basal ganglionic syndrome; and yet another by incoordination (ataxia)—the cerebellar syndrome. Table 4-1 summarizes the main clinical differences between corticospinal and extrapyramidal syndromes.


Neurology_Adams

Neurology_Adams. As an anatomic entity, the basal ganglia have no precise definition. Principally they include the caudate nucleus and the lentiform (lenticular, from its lens-like shape) nucleus with its two subdivisions—the putamen and globus pallidus. Insofar as the caudate nucleus and putamen are really a continuous structure (separated only incompletely by fibers of the internal capsule) and are cytologically and functionally distinct from the pallidum, it is more meaningful to divide these nuclear masses into the striatum (or neostriatum), comprising the caudate nucleus and putamen, and the paleostriatum or pallidum, which has a medial (internal) and a lateral (external) portion. The putamen and pallidum lie on the lateral aspect of the internal capsule, which separates them from the caudate nucleus, thalamus, subthalamic nucleus, and substantia nigra on its medial side (Figs. 4-1 and 4-2). By virtue of their close connections with the caudate and lenticular nuclei, the subthalamic nucleus


Neurology_Adams

Neurology_Adams. thalamus, subthalamic nucleus, and substantia nigra on its medial side (Figs. 4-1 and 4-2). By virtue of their close connections with the caudate and lenticular nuclei, the subthalamic nucleus (nucleus of Luys) and the substantia nigra are included as parts of the basal ganglia. The claustrum and amygdaloid nuclear complex, despite their largely different connections and functions, are sometimes included although they do not participate in any direct way in the modulation of movement.


Neurology_Adams

Neurology_Adams. For reasons indicated further on, some physiologists have expanded the list of basal ganglionic structures to include the red nucleus, the intralaminar thalamic nuclei, and the reticular formations of the upper brainstem. These structures receive direct cortical projections and give rise to rubrospinal and reticulospinal tracts that run parallel to the corticospinal (pyramidal) ones; hence they also were once referred to as extrapyramidal. However, these nonpyramidal linkages are structurally independent of the major extrapyramidal circuits and are better termed parapyramidal systems. As the final links in this circuit—the premotor and supplementary motor cortices—ultimately project onto the motor cortex, they are more aptly referred to as prepyramidal (Thach and Montgomery).


Neurology_Adams

Neurology_Adams. Earlier views of basal ganglionic organization emphasized serial connectivity and the funneling of efferent projections to the ventrolateral thalamus and thence to the motor cortex (Fig. 4-3). The most important basal ganglionic connections and circuitry are indicated in Figs. 4-1, 4-2, and 4-3. The striatum, mainly the putamen, is the receptive part of the basal ganglia, receiving topographically organized fibers from all parts of the cerebral cortex and from the pars compacta (pigmented neurons) of the substantia nigra. The output nuclei of the basal ganglia consist of the medial (internal) pallidum and the pars reticulata (nonpigmented portion) of the substantia nigra (see Fig. 4-3). Further explication of basal ganglionic function can be found in the excellent book by Watts and Koller.


Neurology_Adams

Neurology_Adams. These concepts were based largely on the experimental work of Whittier and Mettler and of Carpenter, in the late 1940s. These investigators demonstrated, in monkeys, that a disorder, which they termed choreoid dyskinesia, could be brought about in the limbs of one side of the body by a lesion localized to in the opposite subthalamic nucleus. They also showed that for such a lesion to provoke dyskinesia, the adjacent pallidum and pallidofugal fibers had to be preserved; that is, a second lesion—placed in the medial segment of the pallidum, in the fasciculus lenticularis, or in the ventrolateral thalamus—abolished the dyskinesia. This experimental hyperkinesia could also be abolished by interruption of the lateral corticospinal tract but not by sectioning of the other motor or sensory pathways in the spinal cord. These observations were interpreted to mean that the subthalamic nucleus exerts an inhibitory or regulating influence on the globus pallidus and ventral thalamus. Removal of


Neurology_Adams

Neurology_Adams. in the spinal cord. These observations were interpreted to mean that the subthalamic nucleus exerts an inhibitory or regulating influence on the globus pallidus and ventral thalamus. Removal of this influence by selective destruction of the subthalamic nucleus is expressed physiologically by an irregular activity that is now identified as chorea, presumably arising from the intact pallidum and conveyed to the ventrolateral thalamic nuclei, thence by thalamocortical fibers to the ipsilateral premotor cortex, and from there, to the motor cortex, all in a serial manner.


Neurology_Adams

Neurology_Adams. A general principle that has withstood the test of time is the central role of the ventrolateral and ventroanterior nuclei of the thalamus. Together, these nuclei form a nexus, not only from the basal ganglia but also from the cerebellum, to the motor and premotor cortex. Thus, both basal ganglionic and cerebellar influences are brought to bear, via thalamocortical fibers, on the corticospinal system and on other descending pathways from the cortex. Direct descending pathways from the basal ganglia to the spinal cord are relatively insignificant.


Neurology_Adams

Neurology_Adams. It is currently proposed on the basis of physiologic, lesional, and pharmacologic studies that there are two main efferent projections from the putamen. There are reasons to conceptualize: (1) a direct efferent system from the putamen to the medial (internal) pallidum and then to the substantia nigra, particularly to the pars reticulata, and (2) an indirect system originating in the putamen that traverses the lateral (external) pallidum and continues to the subthalamic nucleus, with which it has strong reciprocal connection. To these, has been added (3) a hyperdirect pathway that activates the subthalamic nucleus directly from the motor cortex, without the necessity of the intervening striatum.


Neurology_Adams

Neurology_Adams. In most ways, the subthalamic nucleus and lateral pallidum operate as a single functional unit, (at least in terms of the effects of lesions in those locations on parkinsonian symptoms and the neurotransmitters involved. The internal (medial) pallidum (GPi) and reticular part of the substantia nigra can be viewed in a similar unitary way, sharing the same input and output patterns. Within the indirect pathway, an internal loop is created by projections from the subthalamic nucleus to the medial segment of the pallidum and pars reticulata. A second offshoot of the indirect pathway consists of projections from the external (lateral) pallidum (GPe) to the medial pallidonigral output nuclei. A complete account of this intricate connectivity cannot be given, but the main themes outlined here seem valid and are to be found in the review by Obeso and colleagues.


Neurology_Adams

Neurology_Adams. From the internal pallidum, two bundles of fibers reach the thalamus—the ansa lenticularis and the fasciculus lenticularis. The ansa sweeps around the internal capsule; the fasciculus traverses the internal capsule in a number of small fascicles and then continues medially and caudally to join the ansa in the prerubral field. Both of these fiber bundles join the thalamic fasciculus, which then contains not only the pallidothalamic projections but also mesothalamic, rubrothalamic, and dentatothalamic ones. These projections are directed to separate targets in the ventrolateral nucleus of the thalamus and to a lesser extent in the ventral anterior and intralaminar thalamic nuclei. The centromedian nucleus of the intralaminar group projects back to the putamen and, via the parafascicular nucleus, to the caudate. A major projection from the ventral thalamic nuclei to the ipsilateral premotor cortex completes the large cortical–striatal–pallidal–thalamic–cortical motor loop, with


Neurology_Adams

Neurology_Adams. nucleus, to the caudate. A major projection from the ventral thalamic nuclei to the ipsilateral premotor cortex completes the large cortical–striatal–pallidal–thalamic–cortical motor loop, with conservation of the somatotopic arrangement of motor fibers, again emphasizing the nexus of motor control at the thalamic nuclei.


Neurology_Adams

Neurology_Adams. Newer observations have made it apparent that there are a number of parallel basal ganglionic–cortical circuits. These circuits run parallel to the premotor pathway but remain separate anatomically and physiologically. At least five such anatomic connections have been described, each projecting to different portions of the frontal lobe: (1) the prototypical motor circuit, converging on the premotor cortex; (2) the ocular motor circuit, projecting onto the frontal eye fields; two prefrontal circuits: (3) one ending in the dorsolateral prefrontal and (4) the other on the lateral orbitofrontal cortex; and (5) a limbic circuit that projects to the anterior cingulate and medial orbitofrontal cortex.


Neurology_Adams

Neurology_Adams. An additional and essential feature of basal ganglionic structure is the nonequivalence of all parts of the striatum. Particular cell types and zones of cells within this structure appear to mediate different aspects of motor control and to utilize specific neurochemical transmitters, as detailed below under “Pharmacologic Considerations” (see also Albin et al and DeLong). This specialization has taken on further importance with the observation that specific cell types are destroyed preferentially in degenerative diseases such as Huntington chorea.


Neurology_Adams

Neurology_Adams. In simplest physiologic terms, Denny-Brown and Yanagisawa, who studied the effects of ablation of individual extrapyramidal structures in monkeys, concluded that the basal ganglia function as a kind of clearinghouse where, during an intended or projected movement, one set of activities is facilitated and all other unnecessary ones are suppressed. They used the analogy of the basal ganglia as a brake or switch, the tonic inhibitory (“brake”) action preventing target structures from generating unwanted motor activity and the “switch” function referring to the capacity of the basal ganglia to select which of many available motor programs will be active at any given time. Still other theoretical constructs focus on the role of the basal ganglia in the initiation, sequencing, and modulation of motor activity (“motor programming”). Also, it appears that the basal ganglia participate in the constant priming of the motor system, enabling the rapid execution of motor acts without


Neurology_Adams

Neurology_Adams. modulation of motor activity (“motor programming”). Also, it appears that the basal ganglia participate in the constant priming of the motor system, enabling the rapid execution of motor acts without premeditation—for example, hitting a baseball. In most ways, these conceptualizations restate the same notions of balance and selectivity imparted to all motor actions by the basal ganglia.


Neurology_Adams

Neurology_Adams. Physiologic evidence reflects this balanced architecture, one excitatory and the other inhibitory within the individual circuits. The direct striatomedial pallidonigral pathway is activated by glutaminergic projections from the sensorimotor cortex and by dopaminergic nigral (pars compacta)—striatal projections. Activation of this direct pathway inhibits the internal pallidum, which, in turn, disinhibits the ventrolateral and ventroanterior nuclei of the thalamus. As a consequence, thalamocortical drive is enhanced and cortically initiated movements are facilitated. The indirect circuit arises from putaminal neurons that contain gamma-aminobutyric acid (GABA) and smaller amounts of enkephalin. These striatal projections have an inhibitory effect on the medial pallidum, which, in turn, disinhibits the subthalamic nucleus through GABA release, providing subthalamic drive to the internal pallidum and substantia nigra pars reticulata. The net effect is thalamic inhibition, which reduces


Neurology_Adams

Neurology_Adams. the subthalamic nucleus through GABA release, providing subthalamic drive to the internal pallidum and substantia nigra pars reticulata. The net effect is thalamic inhibition, which reduces thalamocortical input to the precentral motor fields and impedes voluntary movement. These complex anatomic and physiologic relationships have been summarized in numerous schematic diagrams similar to Fig. 4-4 and those by Lang and Lozano and by Standaert and Young.


Neurology_Adams

Neurology_Adams. Restated, the current view is that enhanced conduction through the indirect pathway leads to hypokinesia by increasing pallidothalamic inhibition, whereas enhanced conduction through the direct pathway results in hyperkinesia by reducing pallidothalamic inhibition. The direct pathway has been conceived by Marsden and Obeso as facilitating cortically initiated movements and the indirect pathway as suppressing potentially conflicting and unwanted motor patterns. Dopamine released by the pars reticulata of the substantia nigra helps maintain the normal balance between the direct and indirect pathways. In Parkinson disease a loss of dopaminergic input from the substantia nigra diminishes activity in the direct pathway and increases activity in the indirect pathway; the net effect is to increase inhibition of the thalamic nuclei and to reduce excitation of the cortical motor system.


Neurology_Adams

Neurology_Adams. Further insight into these systems and into the mechanism of Parkinson disease came from the discovery that the parkinsonian syndrome is largely reproduced in humans and primates by the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This toxin was discovered when drug abusers self-administered an analogue of meperidine. The molecule binds with high affinity to monoamine oxidase (MAO), an extraneural enzyme that transforms it to pyridinium, a metabolite that is bound by melanin in the dopaminergic nigral neurons and destroys the cells, probably by interfering with mitochondrial function. In monkeys made parkinsonian by the administration of MPTP, electrophysiologic studies have shown increased activity in the internal globus pallidus and decreased activity in the external globus pallidus, as predicted from the above described models. The end result is increased inhibition of thalamocortical neurons.


Neurology_Adams

Neurology_Adams. However, crude lesions of either or both parts of the pallidum, such as infarcts, hemorrhages, and tumors, even beyond their unilateral location, do not cause the full parkinsonian syndrome. Perhaps it is because the subtle imbalance is not reproduced between the internal and external pallidal circuits that exist in Parkinson disease. More specifically, the internal segment is part of the direct and indirect pathway, one excitatory and the other inhibitory, whereas the external segment is only influenced by the indirect pathway. Indeed, striking improvements in parkinsonian symptoms are obtained, paradoxically, by placing lesions in the internal pallidum (pallidotomy) as discussed in Chap. 38.


Neurology_Adams

Neurology_Adams. It is likely that the static model of inhibitory and excitatory pathways and the parsing of a direct and an indirect pathway, as useful as it is as a mnemonic, does not account well for the dynamic activities of the basal ganglia. In particular, the electrical activity of the neurons in these systems oscillate and influence the frequency pattern of firing in other parts of the system, as well as bringing individual cells closer to firing. Another limitation of currently conceived models is that they do not account for the tremor of Parkinson disease. To further complicate matters, the various subtypes of dopamine receptors act in both excitatory and inhibitory ways under different circumstances depending on their location as discussed below. The manner in which excessive or reduced activity of various components of the basal ganglia gives rise to hypokinetic and hyperkinetic movement disorders is discussed further on, under “Symptoms of Basal Ganglia Disease.”


Neurology_Adams

Neurology_Adams. A series of pharmacologic observations have considerably enhanced our understanding of basal ganglionic function and led to a rational treatment of Parkinson disease and other extrapyramidal syndromes. Whereas physiologists had for years failed to discover the functions of the basal ganglia by stimulation and crude ablation experiments, clinicians became aware that certain drugs, such as reserpine and the phenothiazines, could produce extrapyramidal syndromes (e.g., parkinsonism, choreoathetosis, dystonia). These observations stimulated the study of central nervous system (CNS) transmitter substances in general. The current view is that the integrated basal ganglionic control of movement can be best understood by considering, in the context of the anatomy described above, the physiologic effects of neurotransmitters that convey the signals between cortex, striatum, globus pallidus, subthalamic nucleus, substantia nigra, and thalamus.


Neurology_Adams

Neurology_Adams. The most important neurotransmitter substances from the point of view of basal ganglionic function are glutamate, GABA, dopamine, acetylcholine, and serotonin. A more complete account of this subject may be found in the reviews of Penney and Young, of Alexander and Crutcher, and of Rao. The following is what is known with a fair degree of certainty. Glutamate is the neurotransmitter of the excitatory projections from the cortex to the striatum and of the excitatory neurons of the subthalamic nucleus. GABA is the inhibitory neurotransmitter of striatal, pallidal, and substantia nigra (pars reticulata) projection neurons.


Neurology_Adams

Neurology_Adams. Of the catecholamines, dopamine has the most pervasive role but its influence can be excitatory or inhibitory depending on the site of action and the subtype of dopamine receptor. Disturbances of dopamine signaling are essential abnormalities of several CNS disorders including parkinsonism, schizophrenia, attention deficit hyperactivity disorder, and drug abuse. Within the basal ganglia, the areas richest in dopamine are the substantia nigra, where it is synthesized in the nerve cell bodies of the pars compacta, and the termination of these fibers in the striatum. In the most simplified models, stimulation of the dopaminergic neurons of the substantia nigra induces a specific response in the striatum—namely, an inhibitory effect on the already low firing rate of neostriatal neurons.


Neurology_Adams

Neurology_Adams. However, the effects of dopamine have proved even more difficult to resolve, in large part because there are now five known types of postsynaptic dopamine receptors (D1 to D5), each with a particular anatomic distribution and pharmacologic action. This heterogeneity is exemplified in the excitatory effect of dopamine on the small spiny neurons of the putamen and an inhibitory effect on others. Viewed from the perspective of the direct and indirect pathways, dopamine enhances the activity of the former and inhibits the latter, resulting in a net disinhibition of thalamic nuclei and a release of cortical motor function.


Neurology_Adams

Neurology_Adams. The five types of dopamine receptors are found in differing concentration throughout various parts of the brain, each displaying differing affinities for dopamine itself and for various drugs and other agents (Table 4-2; also see Jenner). The D1 and D2 receptors are highly concentrated in the striatum and are the ones most often implicated in diseases of the basal ganglia; D3 in the nucleus accumbens, D4 in the frontal cortex and certain limbic structures, and D5 in the hippocampus and limbic system. In the striatum, the effects of dopamine act as a class of “D1-like” (D1 and D5 subtypes) and “D2-like” (D2, D3, and D4 subtypes) receptors. Activation of the D1 class stimulates adenyl cyclase, whereas D2 receptor binding inhibits this enzyme. Whether dopamine functions in an excitatory or inhibitory manner at a particular synapse is determined by the local receptor. As mentioned earlier, excitatory D1 receptors predominate on the small spiny putaminal neurons that are the origin of the


Neurology_Adams

Neurology_Adams. manner at a particular synapse is determined by the local receptor. As mentioned earlier, excitatory D1 receptors predominate on the small spiny putaminal neurons that are the origin of the direct striatopallidal output pathway, whereas D2 receptors mediate the inhibitory influence of dopamine on the indirect striatopallidal output, as indicated in Fig. 4-4.


Neurology_Adams

Neurology_Adams. Some of the clinical and pharmacologic effects of dopamine are made clear by considering both the anatomic sites of various receptors and their physiologic effects. For example, it appears that drug-induced parkinsonian syndromes and tardive dyskinesias (described further on) are prone to occur when drugs are administered that competitively bind to the D2 receptor, but that the newer antipsychosis drugs, which produce fewer of these effects, have a stronger affinity for the D4 receptor. However, the situation is actually far more complex, in part because of the synergistic activities of D1 and D2 receptors, each potentiating the other at some sites of convergence, and the presence on the presynaptic terminals of nigrostriatal neurons of D2 receptors, which inhibit dopamine synthesis and release.


Neurology_Adams

Neurology_Adams. In contrast to the almost instantaneous actions of glutamate and its antagonist, GABA, the monoamines may have more protracted effects, lasting for seconds or up to several hours. Dopamine and related neurotransmitters therefore have a slower influence through the “second messenger” cyclic adenosine monophosphate (cAMP), which, in turn, controls the phosphorylation or dephosphorylation of numerous intraneuronal G-proteins. These intracellular effects have been summarized by Greengard.


Neurology_Adams

Neurology_Adams. The effects of certain drugs, some no longer in use, are also best comprehended by understanding the manner in which they alter neurotransmitter function. Several drugs—namely reserpine, the phenothiazines, and the butyrophenones (notably haloperidol)—induce prominent parkinsonian syndromes in humans. Reserpine, for example, depletes the striatum and other parts of the brain of dopamine; haloperidol and the phenothiazines work by a different mechanism, probably by blocking dopamine receptors within the striatum.


Neurology_Adams

Neurology_Adams. The basic validity of the physiologic-pharmacologic model outlined here is supported by the observation that excess doses of L-dopa or of a direct-acting dopamine receptor agonist lead to excessive motor activity. Furthermore, the therapeutic effects of the main drugs used in the treatment of Parkinson disease are understandable in the context of neurotransmitter function. To correct the basic dopamine deficiency from a loss of nigral cells that underlies Parkinson disease, attempts were at first made to administer dopamine directly. However, dopamine as such cannot cross the blood–brain barrier and therefore has no therapeutic effect. But its immediate precursor, L-dopa, does cross the blood–barrier and is effective in decreasing the symptoms of Parkinson disease as well as of the above-described MPTP-induced parkinsonism. This effect is enhanced by the addition of an inhibitor of dopadecarboxylase, an important enzyme in the catabolism of dopamine. The addition of an enzyme


Neurology_Adams

Neurology_Adams. above-described MPTP-induced parkinsonism. This effect is enhanced by the addition of an inhibitor of dopadecarboxylase, an important enzyme in the catabolism of dopamine. The addition of an enzyme inhibitor of this type (carbidopa or benserazide) to L-dopa results in an increase of dopamine concentration in the brain, while sparing other organs. The benefit of combining L-dopa with carbidopa is to minimize the systemic side effects of peripheral dopamine, such as nausea, vomiting, and hypotension. Similarly, drugs that inhibit catechol O-methyltransferase (COMT), another enzyme that metabolizes dopamine, prolong the effects of administered L-dopa.


Neurology_Adams

Neurology_Adams. Acetylcholine (ACh), long established as the neurotransmitter at the neuromuscular junction and the autonomic ganglia, is also physiologically active in the basal ganglia. The highest concentration of ACh, as well as of the enzymes necessary for its synthesis and degradation (choline acetyl transferase and acetylcholinesterase), is in the striatum. Acetylcholine is synthesized and released by the large but sparse (Golgi type 2) nonspiny striatal neurons. It has a mixed but mainly excitatory effect on the more numerous spiny neurons within the putamen that constitute the main origin of the direct and indirect pathways described above. It is likely that the effectiveness of atropinic agents—which have been used empirically for many years in the treatment of Parkinson disease and dystonia—depends on their capacity to antagonize ACh at sites within the basal ganglia and in projections from the pedunculopontine nuclei. Acetylcholine also appears to act on the presynaptic membrane of