Neurology_Adams

Neurology_Adams. 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 striatal cells and to influence their release of neurotransmitters, as discussed below. In addition, the basal ganglia contain other biologically active substances—substance P, enkephalin, cholecystokinin, somatostatin, and neuropeptide Y—which enhance or diminish the effects of other neurotransmitters, that is, they act as neuromodulators.


Neurology_Adams

Neurology_Adams. Because of the pharmacologic effects of ACh and dopamine, it was originally postulated by Ehringer and Hornykiewicz (the latter originated the idea) that a functional equilibrium exists in the striatum between the excitatory activity of ACh and the inhibitory activity of dopamine. In Parkinson disease, the decreased release of dopamine by the substantia nigra onto the striatum disinhibits neurons that synthesize ACh, resulting in a predominance of cholinergic activity—a notion supported by the observation that parkinsonian symptoms are aggravated by centrally acting cholinergic drugs and improved by anticholinergic drugs. According to this theory, administration of anticholinergic drugs restores the ratio between dopamine and ACh, with the new equilibrium being set at a lower-than-normal level because the striatal levels of dopamine are low to begin with. This view has been validated in clinical practice in that one observes a beneficial effect on parkinsonian symptoms after the


Neurology_Adams

Neurology_Adams. level because the striatal levels of dopamine are low to begin with. This view has been validated in clinical practice in that one observes a beneficial effect on parkinsonian symptoms after the administration of anticholinergic agents. The use of drugs that enhance dopamine synthesis or its release, or that directly stimulate dopaminergic receptors in the striatum (e.g., pramipexole), represents another more direct method of treating Parkinson disease as outlined in Chap. 38.


Neurology_Adams

Neurology_Adams. The Pathology of Basal Ganglionic Disease


Neurology_Adams

Neurology_Adams. The extrapyramidal motor syndrome as we know it today was first delineated on clinical grounds and so named by S.A.K. Wilson in 1912. In the disease that now bears his name and that he called hepatolenticular degeneration, the most striking abnormality was a bilaterally symmetrical degeneration of the putamen, sometimes to the point of cavitation. To these lesions Wilson correctly attributed the characteristic symptoms of rigidity and tremor. Shortly thereafter, van Woerkom described a similar clinical syndrome in a patient with acquired liver disease (Wilson’s cases were familial), the most prominent lesions again consisting of foci of neuronal degeneration in the striatum. Clinicopathologic studies of Huntington chorea—beginning with those of Meynert (1871) and followed by those of Jelgersma (1908) and Alzheimer (1911)—related the excessive movements and rigidity characteristic of the disease to a loss of nerve cells in the striatum. In 1920, Oskar and Cecile Vogt gave a detailed


Neurology_Adams

Neurology_Adams. (1908) and Alzheimer (1911)—related the excessive movements and rigidity characteristic of the disease to a loss of nerve cells in the striatum. In 1920, Oskar and Cecile Vogt gave a detailed account of the neuropathologic changes in several patients who had been afflicted with choreoathetosis since early infancy; the changes, which they described as a “status fibrosus” or “status dysmyelinatus,” were confined to the caudate and lenticular nuclei. Surprisingly, it was not until 1919 that Tretiakoff demonstrated the underlying cell loss of the substantia nigra in cases of what was then called paralysis agitans and is now known as Parkinson disease. Finally, a series of observations, culminating with those of J. Purdon Martin and later of Mitchell and colleagues, related hemiballismus to lesions in the subthalamic nucleus of Luys and its immediate connections. While these observations have been invaluable, it has become apparent from clinical work that none of the relationships between


Neurology_Adams

Neurology_Adams. in the subthalamic nucleus of Luys and its immediate connections. While these observations have been invaluable, it has become apparent from clinical work that none of the relationships between anatomic loci and movement disorders are exclusive and the same movement disorder can result from lesions at one of several sites.


Neurology_Adams

Neurology_Adams. Another broad perspective on the result of focal damage in the basal ganglia was afforded by Bhatia and Marsden, who reviewed 240 cases based on CT and MRI in which there were lesions in the caudate, putamen, and globus pallidus associated with movement abnormalities. Dystonia was the most common finding, and chorea and parkinsonism were infrequent. It was also notable that a common associated behavioral abnormality was abulia (apathy and loss of initiative), in those with caudate lesions. The deficiencies of this type of case analysis (i.e., the crudeness of early imaging studies obtained without regard to the temporal aspects of the clinical disorder), conceded by the authors, are obvious. We nonetheless find it surprising that choreoathetosis was not more frequent. Needed are detailed anatomic (postmortem) studies of cases in which the disturbances of function were stable for many months or years. However, restating the comments above, there is no consistent association between any


Neurology_Adams

Neurology_Adams. (postmortem) studies of cases in which the disturbances of function were stable for many months or years. However, restating the comments above, there is no consistent association between any type of movement disorder and a particular location in the basal ganglia.


Neurology_Adams

Neurology_Adams. As a prelude to the next section, Table 4-3 summarizes the clinicopathologic correlations of extrapyramidal movement disorders that are accepted by most neurologists; it must be emphasized, however, that there is still some uncertainty as to the finer details.


Neurology_Adams

Neurology_Adams. In broad terms, all motor disorders consist of functional deficits (or negative symptoms) and conversely, excessive motor activity (positive symptoms), the latter being ascribed to the release or disinhibition of the activity of undamaged parts of the motor system. When diseases of the basal ganglia are analyzed along these lines, bradykinesia, hypokinesia, and loss of normal postural reflexes stand out as the primary negative symptoms, and tremor, rigidity, and the involuntary dyskinetic movements of chorea, athetosis, ballismus and dystonia, as the positive ones. Disorders of phonation, articulation, and locomotion due to basal ganglia disease are more difficult to classify. In some instances this group of signs is clearly a consequence of rigidity and postural disorders, whereas in others, where rigidity is slight or negligible, they seem to represent primary deficiencies. The changes in gait related to diseases of the basal ganglia are the result of both fundamental alterations in


Neurology_Adams

Neurology_Adams. where rigidity is slight or negligible, they seem to represent primary deficiencies. The changes in gait related to diseases of the basal ganglia are the result of both fundamental alterations in tone and posture as well as disruption of the more inherent control of walking by the extrapyramidal system. Psychological stress and anxiety generally worsen the abnormal movements in extrapyramidal syndromes, just as relaxation improves them. A role for the basal ganglia in cognitive function and abnormal behavior is hinted at provocatively in Parkinson disease, progressive supranuclear palsy, Tourette syndrome, and other processes, as summarized by Ring and Serra-Mestres. Slowness in thinking (bradyphrenia) in some of these disorders was alluded to earlier, but is inconsistent. Again, it would be an oversimplification to assign primary importance to the presence of depression, dementia, psychosis, and other disturbances in disease of the basal ganglia or to view changes in these structures


Neurology_Adams

Neurology_Adams. be an oversimplification to assign primary importance to the presence of depression, dementia, psychosis, and other disturbances in disease of the basal ganglia or to view changes in these structures as proximate causes of obsessive-compulsive and other behavioral disorders; rather, a role as part of a larger circuitry is likely. All that can be stated is that the basal ganglia modulate complex behavior, but the precise nature of their effect is not known at this time.


Neurology_Adams

Neurology_Adams. The terms hypokinesia and akinesia (the extreme form of hypokinesia) refer to a reduction in the spontaneous movements of an affected part and a failure to engage it freely in the natural actions of the body. In contrast to what occurs in paralysis (the primary symptom of corticospinal tract lesions), strength is not significantly diminished. Also, hypokinesia is unlike apraxia, in which a lesion erases the pattern of movements necessary for an intended act, leaving other actions intact. Hypokinesia is expressed most clearly in the parkinsonian patient where it takes the form of an extreme underactivity (“poverty”) of movement. The frequent automatic, habitual movements observed in the normal individual—such as putting the hand to the face, folding the arms, or crossing the legs—are absent or greatly reduced. In looking to one side, the eyes move, but not the head. In arising from a chair, there is a failure to make the usual small preliminary adjustments, such as pulling the feet


Neurology_Adams

Neurology_Adams. or greatly reduced. In looking to one side, the eyes move, but not the head. In arising from a chair, there is a failure to make the usual small preliminary adjustments, such as pulling the feet back, putting the hands on the arms of the chair, and so forth. Blinking is infrequent. Saliva is swallowed less frequently and drooling results. The face lacks expressive mobility (“masked facies,” or hypomimia). Speech is rapid, mumbling (or “cluttered”), and monotonic, and the voice is soft.


Neurology_Adams

Neurology_Adams. Bradykinesia connotes slowness of movement, another aspect of the same physiologic difficulty as reflected in hypokinesia. Not only is the parkinsonian patient slightly “slow off the mark” (displaying a longer-than-normal interval between a command and the first contraction of muscle—that is, increased reaction time), but the velocity of movement, or the time from onset to completion of movement, is slower than normal. The extremes of hypokinesia or of bradykinesia can result in a complete impediment of movement, akinesia, a sign that may also result from several other disorders of motor function and volitional motor initiation. Hallett equates akinesia with a prolonged reaction time and bradykinesia with a prolonged time of execution. For a time, bradykinesia was attributed to the frequently associated rigidity, which could reasonably hamper all movements, but the limitation of this explanation became apparent when it was discovered that an appropriately placed stereotactic lesion in


Neurology_Adams

Neurology_Adams. associated rigidity, which could reasonably hamper all movements, but the limitation of this explanation became apparent when it was discovered that an appropriately placed stereotactic lesion in a patient with Parkinson disease may abolish rigidity while leaving the hypokinesia unaltered. Thus it appears that apart from their contribution to the maintenance of posture, the basal ganglia provide an essential element for the performance of the large variety of voluntary and semiautomatic actions required for the full repertoire of natural human motility. That cells in the basal ganglia participate in the initiation of movement is also evident from the fact that the firing rates in these neurons increase before movement is detected clinically.


Neurology_Adams

Neurology_Adams. Hallett and Khoshbin, in an analysis of ballistic (rapid) movements in the parkinsonian patient, found that the normal triphasic sequence of agonist–antagonist–agonist activation, as described in the next chapter, is intact but lacks the amplitude (number of activated motor units) to complete the movement normally. Several smaller triphasic sequences are then needed, which slow the movement. The patient experiences these phenomena as not only slowness but also a perceived weakness.


Neurology_Adams

Neurology_Adams. In terms of pathologic anatomy and physiology, bradykinesia may be caused by any process or drug that interrupts the cortico-striato-pallido-thalamic circuit. Clinical examples include reduced dopaminergic input from the substantia nigra to the striatum, as in Parkinson disease; dopamine receptor blockade by neuroleptic drugs; extensive degeneration of striatal neurons, as in striatonigral degeneration and the rigid form of Huntington chorea; and destruction of the medial pallidum, as in Wilson disease. As illustrated in Fig. 4-4B, which gives a schematic representation of the hypokinetic state of Parkinson disease, changes in the cortico-striato-pallido-thalamic circuit (in this case mainly the direct striatopallidal pathway) can be interpreted in terms of altered neurochemical and resultant physiologic connectivity within the basal ganglia. The reciprocal situation, enhanced motor activity, is summarized in the analogous diagram for Huntington disease (Fig. 4-4C), in which a


Neurology_Adams

Neurology_Adams. resultant physiologic connectivity within the basal ganglia. The reciprocal situation, enhanced motor activity, is summarized in the analogous diagram for Huntington disease (Fig. 4-4C), in which a reduction in the activity of the indirect striatopallidal pathway leads to enhanced excitatory motor drive in the thalamocortical motor pathway.


Neurology_Adams

Neurology_Adams. A number of other disorders of voluntary movement may also be observed in patients with diseases of the basal ganglia. A persistent voluntary contraction of hand muscles, as in holding a pencil, may fail to be inhibited, so that there is interference with the next willed movement. This has been termed tonic innervation, or blocking, and may be brought out by asking the patient to repetitively open and close a fist or tap a finger. Attempts to perform an alternating sequence of movements may be blocked at one point, or there may be a tendency for the voluntary movement to adopt the frequency of a coexistent tremor (entrainment). Disorders of Postural Fixation, Equilibrium, and Righting


Neurology_Adams

Neurology_Adams. These deficits are also demonstrated most clearly in the parkinsonian patient. The prevailing posture is one of involuntary flexion of the trunk, limbs and the neck, which gives the parkinsonian individual a characteristic appearance, even at a distance from the observer, as described by Parkinson, “A propensity to bend the trunk forwards, and to pass from a walking to a running pace.” Anticipatory and compensatory righting reflexes, referring to mechanisms that maintain upright posture, are also manifestly impaired. This occurs early in the course of progressive supranuclear palsy and later in Parkinson disease. The inability of the patient to make appropriate postural adjustments to tilting or falling and his inability to move from the reclining to the standing position are closely related phenomena. A gentle push on the patient’s sternum or a tug on the shoulders may cause a fall or start a series of small corrective steps that the patient cannot control (festination). These basal


Neurology_Adams

Neurology_Adams. phenomena. A gentle push on the patient’s sternum or a tug on the shoulders may cause a fall or start a series of small corrective steps that the patient cannot control (festination). These basal ganglionic postural abnormalities are not attributable to weakness or to defects in proprioceptive, labyrinthine, or visual function, the principal forces that control the normal posture of the head and trunk.


Neurology_Adams

Neurology_Adams. In the form of altered muscle tone known as rigidity, the muscles are continuously or intermittently firm and tense. Although brief periods of electromyographic silence can be obtained in selected muscles by persistent attempts to relax the limb, there is obviously a low threshold for involuntary sustained muscle contraction, and this is present during most of the waking state, even when the patient appears quiet and relaxed. In contrast to spasticity, the increased resistance on passive movement that characterizes rigidity is not preceded by an initial “free interval” and has an even or uniform quality throughout the range of movement of the limb, like that experienced in bending a lead pipe or pulling a strand of toffee. The contrasting terms clasp-knife for spasticity and lead-pipe for rigidity have been applied to the examiner’s physical perception on attempting to smoothly manipulate the patient’s limb through an arc of movement. Moreover, the rigidity of extrapyramidal disorder


Neurology_Adams

Neurology_Adams. rigidity have been applied to the examiner’s physical perception on attempting to smoothly manipulate the patient’s limb through an arc of movement. Moreover, the rigidity of extrapyramidal disorder is not velocity dependent, as it is in spasticity. The tendon reflexes are not enhanced in the rigid limb as they are in spasticity and, when released, the limb does not resume its original position, as happens in spasticity.


Neurology_Adams

Neurology_Adams. Rigidity usually involves both flexor and extensor muscle groups, but it tends to be more prominent in muscles that maintain a flexed posture, that is, in the flexor muscles of trunk and limbs. It appears to be somewhat greater in the large muscle groups, but this may be merely a matter of muscle mass. Certainly the small muscles of the face and tongue and even those of the larynx are often affected by rigidity. Concordant with the physical examination, in the electromyographic tracing, motor-unit activity is more continuous in rigidity than in spasticity, persisting even after apparent relaxation.


Neurology_Adams

Neurology_Adams. A special feature that may accompany rigidity, first noted by Negro in 1901, is the cogwheel phenomenon. When the hypertonic muscle is passively stretched, for example, when the hand is dorsiflexed, one encounters a rhythmically interrupted, ratchet-like resistance. Many believe that this phenomenon represents an underlying tremor that, if not manifestly present, emerges faintly during manipulation. In that case it would not be a fundamental property of rigidity and would be found in many tremulous states. However, numerous instances of severe tremor with minimally perceptible cogwheeling, and the opposite, suggest to us on clinical grounds that the phenomenon may be more complex.


Neurology_Adams

Neurology_Adams. Rigidity is characteristically variable in severity at different times; in some patients with involuntary movements, particularly in those with chorea or dystonia, the limbs may actually be intermittently or persistently hypotonic. Rigidity is a prominent feature of many basal ganglionic diseases, such as Parkinson disease, Wilson disease, striatonigral degeneration (multiple system atrophy), progressive supranuclear palsy, dystonia musculorum deformans (discussed further on and in Chap. 38), exposure to neuroleptic drugs, and mineralization of the basal ganglia (Fahr disease).


Neurology_Adams

Neurology_Adams. Another distinctive type of variable resistance to passive movement is one in which the patient seems unable to relax a group of muscles on request. When the limb muscles are passively stretched, the patient appears to actively resist the movement (gegenhalten, paratonia, or oppositional resistance). Natural relaxation normally requires concentration on the part of the patient. If there is inattentiveness—as happens with diseases of the frontal lobes, dementia, or other confusional states—this type of oppositional resistance may raise a question of parkinsonian rigidity. This is not a manifestation of basal ganglia disorder per se but may indicate that the connections of the basal ganglia to the frontal lobes are impaired. A similar difficulty in relaxation is observed normally in small children. Also not to be mistaken for rigidity or paratonia is the “waxy flexibility” displayed by the psychotic-catatonic patient when a limb placed in a suspended position is maintained for minutes


Neurology_Adams

Neurology_Adams. children. Also not to be mistaken for rigidity or paratonia is the “waxy flexibility” displayed by the psychotic-catatonic patient when a limb placed in a suspended position is maintained for minutes in the identical posture (flexibilitas cerea).


Neurology_Adams

Chorea, Athetosis, Ballismus, Dystonia

Neurology_Adams. Chorea, Athetosis, Ballismus, Dystonia


Neurology_Adams

Neurology_Adams. These involuntary hyperkinetic symptoms are described as discrete clinical phenomenon, readily distinguishable from the others. Although distinctions are made between chorea, athetosis, and dystonia, even their most prominent differences—the discreteness and rapidity of choreic movements and the slowness of athetotic ones—are more apparent than real. As pointed out by S.A. Kinnier Wilson, involuntary movements may follow one another in such rapid succession that they become confluent and therefore appear to be slow. In reality, they usually occur together or blend imperceptibly into each other and have many points of clinical similarity. There are reasons to believe that they have a common anatomic and physiologic basis although distinct sites in the brain have been tentatively implicated for each. One must be mindful that chorea, athetosis, and dystonia are symptoms and are not to be equated with disease entities that happen to incorporate one of these terms in their names (e.g.,


Neurology_Adams

Neurology_Adams. for each. One must be mindful that chorea, athetosis, and dystonia are symptoms and are not to be equated with disease entities that happen to incorporate one of these terms in their names (e.g., Huntington chorea, dystonia musculorum deformans). Here the discussion is limited to the symptoms. The diseases of which these symptoms are a part are considered mainly in Chap. 39.


Neurology_Adams

Neurology_Adams. Somewhat more ambiguous but in common clinical use is the term dyskinesia. It encompasses all the active movement phenomena that are a consequence of disease of the basal ganglia, usually implying an element of dystonia. It has also been used to refer more specifically to the undifferentiated excessive movements that are induced in Parkinson patients at the peak of L-dopa effect and to numerous dystonic and athetotic movements that may follow the use of neuroleptic drugs (“tardive dyskinesias”) that are discussed further on.


Neurology_Adams

Neurology_Adams. Derived from the Greek word meaning “dance,” chorea refers to involuntary arrhythmic movements of a forcible, rapid, jerky type. These movements may be simple or quite elaborate and of variable distribution. Although the movements are purposeless, the patient may incorporate them into a deliberate act, as if to make them less noticeable. When superimposed on voluntary actions, they may assume an exaggerated and bizarre character. Grimacing and peculiar respiratory sounds may be other expressions of the disorder. Usually the movements are discrete, but if very numerous, they become confluent and then resemble athetosis, as described below. In moments when the involuntary movements are held in abeyance, volitional movements of normal strength are possible; but they also tend to be excessively quick and poorly sustained. The limbs are often slack or hypotonic and because of this, the knee jerks tend to be pendular; in other words, with the patient sitting on the edge of the examining


Neurology_Adams

Neurology_Adams. quick and poorly sustained. The limbs are often slack or hypotonic and because of this, the knee jerks tend to be pendular; in other words, with the patient sitting on the edge of the examining table and the foot free of the floor, the leg swings back and forth several times in response to a tap on the patellar tendon, rather than once or twice, as it does normally. A choreic movement may be superimposed on the reflex movement, checking it in flight, so to speak.


Neurology_Adams

Neurology_Adams. Chorea differs from myoclonus mainly with respect to the speed of the movements; the myoclonic jerk is much faster and may involve single muscles or part of a muscle as well as groups of muscles. Failure to appreciate these differences often results in an incorrect diagnosis. The hypotonia as well as the pendular reflexes that accompany chorea may also occur in disturbances of cerebellar function. Lacking, however, are “intention” tremor and true incoordination or ataxia. In some circumstances, it may be necessary to distinguish chorea from myoclonus.


Neurology_Adams

Neurology_Adams. Table 4-4 lists diseases characterized mainly by chorea or localized lesions that may at times cause chorea. Of the degenerative conditions, chorea is a major feature of Huntington disease, in which the movements tend more typically to be a merging of choreiform and the below-described athetotic (choreoathetotic) motions. Not infrequently, chorea has its onset in late life without the other identifying features of Huntington disease. It is then referred to as senile chorea, a term that is hardly helpful in understanding the process. Its relation to Huntington chorea in any individual case is settled by genetic testing. A number of less common degenerative conditions are associated with chorea, among them dentatorubropallidoluysian atrophy (DRPLA) and a form of chorea associated with acanthocytosis of red blood cells. Also, there is an inherited form of chorea of childhood onset without dementia that has been referred to as benign hereditary chorea. There may be subtle additional


Neurology_Adams

Neurology_Adams. acanthocytosis of red blood cells. Also, there is an inherited form of chorea of childhood onset without dementia that has been referred to as benign hereditary chorea. There may be subtle additional ataxia of gait, as noted by Breedveld and colleagues. These are discussed in Chap. 38.


Neurology_Adams

Neurology_Adams. Typical choreic movements are the dominant feature of several immune-related conditions, perhaps the best characterized being Sydenham chorea that is strongly linked to streptococcal infection, mainly in women. Striatal abnormalities, usually transient and rarely persistent, have been demonstrated by MRI (Emery and Vieco). It is perhaps not surprising that antibodies directed against cells of the basal ganglia have been detected in both acute and late Sydenham chorea (Church et al). Following from the connection to streptococcal infection and the detection of these antibodies, it has been suggested in recent years that the spectrum of poststreptococcal disorders can be extended to tic and obsessive-compulsive behavior in children (PANDAS syndrome discussed in a later section). In these cases the neurologic problems are said to arise suddenly, subside, and return with future streptococcal infections, as discussed further on. This seems unlikely to explain chorea in adults. There also


Neurology_Adams

Neurology_Adams. the neurologic problems are said to arise suddenly, subside, and return with future streptococcal infections, as discussed further on. This seems unlikely to explain chorea in adults. There also exists a variety of chorea associated with pregnancy (chorea gravidarum), which in the past had a close linkage to prior episodes of Sydenham chorea. Alternatively, pregnancy may expose lupus-related chorea or be concordant with the onset of Huntington chorea. However, the elicitation of chorea by oral contraceptives in the modern era, as noted below, suggests a hormonal rather than immune causation in many cases. There have been instances of paraneoplastic chorea associated in a very few cases with lung cancer and anti-CRMP or anti-Hu antibodies of the type described as reported by O’Toole and colleagues and by Vernino et al. The paraneoplastic variety may combine several aspects of chorea with athetosis, ballismus, or dystonia; inflammatory lesions are found in the striatum (see Chap. 30).


Neurology_Adams

Neurology_Adams. The use of oral contraceptives sometimes elicits chorea in an otherwise healthy young woman, but many such patients have underlying systemic lupus erythematosus and antiphospholipid antibodies. Whether the chorea (usually unilateral) is the result of a small infarction (as suggested by a mild hemiparesis on the affected side) or is an immunologic condition is not settled. The reemergence of chorea in these circumstances as steroids are withdrawn or birth control pills are introduced suggests a more complex process than simply a small, deep infarction—perhaps something akin to Sydenham chorea as discussed above. A connection between hemichorea and the antiphospholipid syndrome alone, without lupus, is more tenuous.


Neurology_Adams

Neurology_Adams. The chronic administration of phenothiazine drugs or haloperidol (or an idiosyncratic reaction to these drugs) is a common cause of extrapyramidal movement disorders of all types, including chorea; these may become manifest during use of the drug or in a delayed “tardive” fashion, as already mentioned. The newer antipsychosis drugs (the atypical neuroleptics) have been less frequently associated with the problems. Excess dopamine administration in advanced Parkinson disease is perhaps the most common cause of a choreiform dyskinesia in neurologic practice, but the movements tend to be more complex and continuous than those seen in chorea. The use of phenytoin or other anticonvulsant drugs may cause chorea in sensitive individuals. A transitory chorea may occur in the course of an acute metabolic derangement, mainly with hyperosmolar hyperglycemia, hypoglycemia, or hyponatremia, and with the inhalation of crack cocaine.


Neurology_Adams

Neurology_Adams. Rarely, chorea complicates hyperthyroidism, polycythemia vera, lupus erythematosus or some forms of cerebral arteritis. AIDS has emerged as a cause of a few cases of subacute progressive movement disorders that are initially asymmetrical. The usual associations in AIDS have been with focal lesions in or near basal ganglionic structures such as toxoplasmosis, progressive multifocal leukoencephalopathy, and lymphoma, but a number of instances of chorea are not explained by any of these focal lesions. A number of rare paroxysmal kinesigenic disorders, discussed later in this chapter, may have a choreic component. Chorea may be limited to one side of the body (hemichorea). When the involuntary movements involve proximal limb muscles and are of wide range and flinging in nature, the condition is called hemiballismus (see further on under that heading). A cerebral infarction is the usual cause of both of these disorders.


Neurology_Adams

Neurology_Adams. The review by Piccolo and colleagues puts the frequency of the various causes of chorea in perspective. Of consecutive neurologic admissions to two general hospitals they identified 23 cases of chorea, of which 5 were drug induced, 5 were AIDS related, and 6 were caused by stroke. Sydenham chorea and arteritis were each found in 1 case. In 4 cases no cause could be determined, and 1 proved to be Huntington disease.


Neurology_Adams

Neurology_Adams. The precise anatomic basis of chorea is often uncertain or at least inconsistent. Transient chorea or ballismus arises from infarctions in any part of the striatum, particularly in the caudate, on the side opposite to the movement. In Huntington chorea, there are obvious lesions in the caudate nucleus and putamen. Yet one often observes vascular lesions in these parts without chorea. The localization of lesions in Sydenham chorea and other choreic diseases has not been determined beyond a generalized disturbance in the striatum, which is evident on some imaging studies. It is of interest that in instances of chorea related to acute metabolic disturbances, there are sometimes small infarctions in the basal ganglia or metabolic changes in the lenticular nucleus, as shown by imaging studies. One suspects from their close clinical similarity that chorea and hemiballismus (see below) relate to disorders of the same system of neurons.


Neurology_Adams

Neurology_Adams. This term stems from a Greek word meaning “unfixed” or “changeable.” The condition is characterized by an inability to sustain the fingers and toes, tongue, or any other part of the body in one position. The maintained posture is interrupted by relatively slow, writhing or twisting, sinuous, purposeless movements that have a tendency to flow into one another. As a rule, the abnormal movements are most pronounced in the digits and hands, face, tongue, and throat, but no group of muscles is spared. One can detect as the basic patterns of movement an alternation between extension–pronation and flexion–supination of the arm and between flexion and extension of the fingers, the flexed and adducted thumb being trapped by the flexed fingers as the hand closes. Other characteristic movements are eversion–inversion of the foot, retraction and pursing of the lips, twisting of the neck and torso, and alternate wrinkling and relaxation of the forehead or forceful opening and closing of the


Neurology_Adams

Neurology_Adams. are eversion–inversion of the foot, retraction and pursing of the lips, twisting of the neck and torso, and alternate wrinkling and relaxation of the forehead or forceful opening and closing of the eyelids. The movements appear as slower than those of chorea, but all gradations between the two are seen; in some cases, it is impossible to distinguish between them, hence the term choreoathetosis. An apt description could be of a moving dystonia (see below). Discrete voluntary movements of the hand are executed more slowly than normal, and attempts to perform them may result in a co-contraction of antagonistic muscles and a spread (overflow) of contraction to muscles not normally required in the movement. The overflow appears related to a failure of the striatum to suppress the activity of unwanted muscle groups. Some forms of athetosis occur only during the performance of projected movement (intention or action athetosis).


Neurology_Adams

Neurology_Adams. Athetosis may affect all four limbs or may be unilateral, especially in children who have suffered a hemiplegia at an early time in life (posthemiplegic athetosis). Many athetotic patients with destructive focal brain lesions exhibit variable degrees of rigidity and motor deficit as a result of associated corticospinal tract disease; these may account for the slower quality in these patients of athetosis compared to chorea. In other patients with generalized choreoathetosis, as pointed out above, the limbs may be intermittently hypotonic.


Neurology_Adams

Neurology_Adams. The combination of athetosis and chorea of all four limbs is a cardinal feature of Huntington disease and of a state known as double athetosis, a form of cerebral palsy that begins in childhood. Athetosis appearing in the first years of life is usually the result of a congenital or postnatal condition such as hypoxia or, now rarely, kernicterus. Postmortem examinations in some of the cases have disclosed a unique pathologic change, status marmoratus, of probable hypoxic etiology in the striatum (see Chap. 37). In other cases, of probable kernicteric (hyperbilirubinemic) etiology, there is a loss of nerve cells and myelinated fibers—a status dysmyelinatus—in the same regions. In adults, athetosis may occur as an episodic or persistent disorder in hepatic encephalopathy, as a manifestation of chronic intoxication with phenothiazines or haloperidol, and as a feature of certain degenerative diseases, most notably Huntington chorea but also Wilson disease, Leigh disease, and other


Neurology_Adams

Neurology_Adams. of chronic intoxication with phenothiazines or haloperidol, and as a feature of certain degenerative diseases, most notably Huntington chorea but also Wilson disease, Leigh disease, and other mitochondrial disease variants; less frequently athetosis may be seen with Niemann-Pick (type C) disease, Kufs disease, neuroacanthocytosis, and ataxia telangiectasia, all of which are described in later chapters. It may also occur as an effect of excessive L-dopa in the treatment of Parkinson disease, in which case it appears to be caused by a decrease in the activity of the subthalamic nucleus and the internal segment of the globus pallidus (Mitchell et al). Athetosis, usually in combination with chorea, may occur rarely in patients with AIDS and in those taking antiepileptic drugs. Localized forms of athetosis may occasionally follow vascular lesions of the lenticular nucleus or thalamus, as in the cases described by Dooling and Adams.


Neurology_Adams

Neurology_Adams. This term designates uncontrollable, large amplitude, poorly patterned flinging movement of an entire limb. As remarked earlier, it is closely related to chorea and athetosis, indicated by the frequent coexistence of these movement abnormalities and the tendency for ballismus to blend into a less-obtrusive choreoathetosis of the distal parts of the affected limb. Ballistic movements are usually unilateral (hemiballismus) and the result of an acute lesion of or near the contralateral subthalamic nucleus or immediately surrounding structures (infarction or hemorrhage, less often a demyelinative or other lesion). Rarely, a transitory form is linked to a subdural hematoma or thalamic or parietal lesion. The flinging movements may be almost continuous or intermittent, occurring several times a minute, and of such dramatic appearance that it is not unusual for them to be regarded as hysterical in nature.


Neurology_Adams

Neurology_Adams. Bilateral ballismus is infrequent and usually asymmetrical; here a metabolic disturbance, particularly nonketotic hyperosmolar coma, is the usual cause. In combination with choreoathetosis, a paraneoplastic process is another rare cause. When ballismus persists for weeks on end, as it often did before effective treatment became available, the continuous forceful movements resulted in exhaustion, weight loss, and even death. In most cases, medication with haloperidol or phenothiazine suppresses the violent movements. In extreme cases, stereotactic lesions or implanted stimulating electrodes placed in the ventrolateral thalamus and zona incerta have proved effective (Krauss and Mundinger).


Neurology_Adams

Neurology_Adams. Dystonia is an unnatural spasmodic movement or posture that puts the limb in a twisted position. It is often patterned, repetitive or tremulous and can be initiated or worsened by attempted movement. There is unwanted overflow contraction of adjacent muscles and a common feature is involuntary co-contraction of agonist and antagonist muscles. Dystonia may take the form of an overextension or overflexion of the hand, inversion of the foot, lateral flexion or retroflexion of the head, torsion of the spine with arching and twisting of the back, forceful closure of the eyes, or a fixed grimace (Fig. 4-5).


Neurology_Adams

Neurology_Adams. Dystonia, like athetosis, may vary considerably in severity and may show striking fluctuations in individual patients. Dystonia may be limited to the facial, cervical, or trunk muscles or to those of one limb, and it may cease when the body is in repose and during sleep. Severe instances result in grotesque movements and distorted positions of the body; sometimes the whole musculature seems to be thrown into spasm by an effort to move an arm or to speak. In its early stages it may be interpreted as an annoying mannerism or hysteria, and only later, in the face of persisting postural abnormality, lack of the usual psychologic features of hysteria, and the emerging character of other aspects of an underlying illness, is the correct diagnosis made.


Neurology_Adams

Neurology_Adams. Causes of generalized dystonia (see Table 4-5) Generalized dystonia is seen in its most pronounced form as an uncommon heritable disease, dystonia musculorum deformans, which is associated with a mutation in the DYT gene. It was in relation to this disease that Oppenheim and Vogt in 1911 introduced the term dystonia. Dystonia also occurs as a manifestation of many other diseases, each of which is characteristic of a certain age group. These include the aforementioned double athetosis caused by hypoxic damage to the fetal or neonatal brain (a form of cerebral palsy), kernicterus, pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz disease), Huntington disease, Wilson disease, lysosomal storage diseases, striatopallidodentatal calcification (Fahr disease, sometimes caused by hypoparathyroidism), certain forms of thyroid disease, and exposure to neuroleptic drugs, as discussed below.


Neurology_Adams

Neurology_Adams. A distinct subset of patients with an idiopathic dystonia (Segawa disease, described also by Nygaard et al and discussed in Chap. 38) responds to extremely small doses of L-dopa. This disorder is familial, usually autosomal dominant, and the dystonia-athetosis may be combined with elements of parkinsonism. Marked diurnal fluctuation of symptoms is characteristic, with the movement disorder worsening as the day wears on and improving with sleep. Another rare hereditary dystonia, termed rapid-onset dystonia-parkinsonism, has its onset in adolescence or early adulthood and is of interest because of the rapid evolution, at times within an hour but more often over days, of severe dystonic spasms, dysarthria, dysphagia, and postural instability with bradykinesia (Dobyns et al). Dystonia is a component of a number of obscure multisystem degenerations that may include diverse features such as optic neuropathy and striatal necrosis.


Neurology_Adams

Neurology_Adams. A frequent cause of acute generalized dystonic reactions, more so in the past, had been from exposure to the class of neuroleptic drugs—phenothiazines, butyrophenones, or metoclopramide—and even with the newer agents such as olanzapine, which have the advantage of producing these side effects less frequently. A characteristic, almost diagnostic, example of the acute drug-induced dystonias consists of retrocollis (forced extension of the neck), arching of the back, internal rotation of the arms, and extension of the elbows and wrists—together simulating opisthotonos. These reactions respond relatively predictably to diphenhydramine or benztropine. L-Dopa, calcium channel blockers, and a number of antiepileptic drugs and anxiolytics are among a long list of other medications may on occasion induce dystonia, as listed in Table 4-5. The acute dystonic drug reactions are idiosyncratic and probably now as common as the tardive dyskinesias that had in the past followed long-standing use of a


Neurology_Adams

Neurology_Adams. induce dystonia, as listed in Table 4-5. The acute dystonic drug reactions are idiosyncratic and probably now as common as the tardive dyskinesias that had in the past followed long-standing use of a medication.


Neurology_Adams

Neurology_Adams. In the literature, there have been reported numerous cases of limb injury and subsequent reflex sympathetic dystrophy (see Chap. 10) that were accompanied by a variety of movement disorders, particularly dystonia. The nature and mechanism of this association are uncertain. Finally, a peculiar and dramatic spasm of a limb or the entire body may be seen in patients with multiple sclerosis. The movements have aspects of dystonia and may be provoked by hyperventilation but they may not be, strictly speaking, dystonic. They are most likely to occur in patients with large demyelinative lesions of the cervical spinal cord.


Neurology_Adams

Neurology_Adams. Restricted or fragmentary forms of dystonia are the types most commonly encountered in clinical practice. Characteristically the spasms involve only the orbicularis oculi and face or mandibular muscles (blepharospasm-oromandibular dystonia), tongue, cervical muscles (torticollis), hand (writer’s cramp), or foot. There may be an associated tremor, or tremor may be the only manifestation of an early dystonia. These are described further on and in Chap. 38.


Neurology_Adams

Neurology_Adams. Hemidystonia represents an unusual form of acquired movement that, in our experience, is rarely pure. In an analysis of 33 of their own cases and 157 previously published ones, Chuang and colleagues found stroke, mainly in the contralateral putamen, to be most often responsible. Traumatic and perinatal damage accounted for several cases and a large proportion had no lesions found by imaging tests. In traumatic cases, there was a delay of several years between the injury and the start of the movements; these authors also commented on the resistance of this syndrome to drug treatment.


Neurology_Adams

Neurology_Adams. In the focal dystonias, the most effective treatment has proved to be the periodic injection of botulinum toxin into the affected muscles as discussed earlier and emphasized later in the chapter. The acute dystonic drug reactions are treated as noted above. Numerous drugs have been used to treat idiopathic chronic generalized dystonia, with a notable lack of success. Fahn reported beneficial effects (more so in children than in adults) with the anticholinergic agents, trihexyphenidyl, benztropine, and ethopropazine given in large doses—which are achieved by increasing the medications very gradually.


Neurology_Adams

Neurology_Adams. The drug-induced tardive dyskinesias require specialized treatment, as described in later chapters and further on. Tetrabenazine and reserpine, centrally active monoamine-depleting agents, are effective. The offending drug may be at first stopped in patients who have not already ceased taking it, but this often leads to worsening of the movements. Reinstitution of the offending drug or high doses of anticholinergic agents is then sometimes necessary but is only partially effective, and requires that the patient tolerate the other effects of the medication such as sedation and parkinsonism. The problem has become less frequent with the introduction of the newer classes of antipsychosis drugs.


Neurology_Adams

Neurology_Adams. Stereotactic surgery on the pallidum and ventrolateral thalamus, a treatment introduced by Cooper in the middle of the last century, had generally positive but unpredictable results in generalized dystonia. In recent years there has been a renewed interest in a modern derivative of this form of treatment, deep brain stimulation. In a controlled trial, Vidailhet and colleagues demonstrated the effectiveness of this approach by stimulating the posteroventral globus pallidus bilaterally. Their patients had an average improvement of 50 percent on most scores of dystonic movement over 1 year. Increasingly, this is the method resorted to in cases of severe generalized dystonia.


Neurology_Adams

Neurology_Adams. Under the names paroxysmal kinesigenic dyskinesia, familial paroxysmal choreoathetosis, and periodic dystonia, among others, are a number of uncommon sporadic or familial disorders characterized by paroxysmal attacks of choreoathetotic movements or dystonic spasms of the limbs and trunk. Both children and young adults are affected.


Neurology_Adams

Neurology_Adams. There are three main forms of familial paroxysmal choreoathetosis and dystonia. Various genes and mutations have been implicated, some of which involve ion channels. One clinical type, which has an autosomal dominant (less often recessive) pattern of inheritance and a tendency to affect males, begins in adolescence or earlier and abates later in life. It is characterized by numerous brief (several minutes) attacks of dystonia or choreoathetosis provoked by sudden movement, startle, or hyperventilation—hence the name paroxysmal kinesigenic choreoathetosis. There may be many dozens of attacks per day or occasional ones. This disorder responds well to antiepileptic medication, particularly to phenytoin and carbamazepine. Mutations of PRRT2, the proline-rich transmembrane protein, have been identified as the cause in some families and link the disease to a variety of infantile convulsions as summarized by Gardiner and colleagues.


Neurology_Adams

Neurology_Adams. In a second nonkinesigenic type, such as described by Mount and Reback and subsequently by Lance and by Plant et al, the attacks take the form of persistent (5 min to 4 h) dystonic spasms and reportedly have been precipitated by the ingestion of alcohol or coffee or by fatigue but not by movement. The attacks may be predominantly one sided or bilateral. Attacks may occur every several days or be separated by years. A favorable response to benzodiazepines (clonazepam) has been reported, even when the drug is given on alternate days (Kurlan and Shoulson). This form of the disease is inherited as an autosomal dominant trait; a few families have displayed diplopia and spasticity and others have shown a familial tendency to infantile convulsions. There are several variations of this nonkinesigenic illness, each with a different implicated gene mutation.


Neurology_Adams

Neurology_Adams. A third type, formerly thought to be a variant of the Mount-Reback type mentioned above, is precipitated by prolonged exercise. In addition to a response to benzodiazepines, it has the unique characteristic of improving with acetazolamide.


Neurology_Adams

Neurology_Adams. More common than these familial dyskinesias are sporadic cases secondary to focal brain lesions such as stroke, trauma, encephalitis, perinatal anoxia, multiple sclerosis, HIV encephalitis or as a result of associated toxoplasmosis, lymphoma; and also generalized metabolic disorders such as hypoparathyroidism, thyrotoxicosis, and particularly, nonketotic hyperosmolarity. Demirkirian and Jankovic classified the acquired paroxysmal dyskinesias according to the duration of each attack and the event or activity that precipitates the abnormal movements (kinesigenic, nonkinesigenic, exertional, or hypnagogic). As with the familial cases, the acquired kinesigenically induced movements often improve with antiepileptic drugs; some cases respond particularly to clonazepam.


Neurology_Adams

Neurology_Adams. The most severe instances of paroxysmal dyskinesia in our experience have been related to the previously mentioned multiple sclerosis (“tetanoid spasms”), and from the secondary brain lesions of HIV. These patients were relatively unresponsive to medications. Also, it should be recalled that oculogyric crises and other nonepileptic spasms have occurred episodically in patients with postencephalitic parkinsonism; these phenomena are now rarely seen with acute and chronic phenothiazine intoxication and with Niemann-Pick disease (type C).


Neurology_Adams

Neurology_Adams. Tremor may be defined as involuntary rhythmic oscillatory movement produced by alternating or irregularly synchronous contractions of reciprocally innervated muscles. Its rhythmic quality distinguishes tremor from the other involuntary movements described earlier, and its oscillatory nature distinguishes it from myoclonus and asterixis. The many varieties of tremor can be considered in terms of their frequency, amplitude, location, and positional activation, and the enhancement or attenuation of the tremor by certain drugs. In some processes, such as Parkinson disease, more than one tremor may be displayed and tremor may be a component of other movement disorders such as dystonia and cerebellar ataxia. The characteristics of the main tremors seen in practice are summarized in Table 4-6.


Neurology_Adams

Neurology_Adams. A normal, or physiologic, tremor is embedded in the motor system. The movement is so fine that it can barely be seen by the naked eye, and then only if the fingers are firmly outstretched; asking the patient to aim a laser pointer at a distant target will often expose the tremor. It is present in all contracting muscle groups and persists throughout the waking state and even in certain phases of sleep. It ranges in frequency between 8 and 13 Hz, the dominant rate being 10 Hz in adulthood and somewhat less in childhood and old age. Several hypotheses have been proposed to explain physiologic tremor, a traditional one being that it reflects the passive vibration of body tissues produced by mechanical activity of cardiac origin, but this cannot be the whole explanation. As Marsden has pointed out, several additional factors—such as spindle input, the unfused grouped firing rates of motor neurons, and the natural resonating frequencies and inertia of the muscles and other structures—are


Neurology_Adams

Neurology_Adams. out, several additional factors—such as spindle input, the unfused grouped firing rates of motor neurons, and the natural resonating frequencies and inertia of the muscles and other structures—are probably of greater importance. Certain abnormal tremors, namely, the metabolic varieties of postural or action tremor and at least one type of familial tremor, are considered by some to be variants or exaggerations of physiologic tremor—that is, “enhanced physiologic tremor,” as discussed further on.


Neurology_Adams

Neurology_Adams. In patients with pathologic tremor of almost any type, Narabayashi has recorded rhythmic burst discharges of unitary cellular activity in the nucleus intermedius ventralis of the thalamus (as well as in the medial pallidum and subthalamic nucleus) synchronous with the beat of the tremor. Neurons that exhibit the synchronous bursts are arranged somatotopically and respond to kinesthetic impulses from the muscles and joints involved in the tremor but that is not to say that there is a causal relationship between this activity and the tremor. A stereotaxic lesion in this region of the thalamus abolishes the tremor. The effectiveness of a thalamic lesion may be a result of interruption of pallidothalamic and dentatothalamic projections or, more likely, of projections from the ventrolateral thalamus to the premotor cortex, as the impulses responsible for tremor are ultimately transmitted by the lateral corticospinal tract. Some of what is known about the physiology of specific tremors is


Neurology_Adams

Neurology_Adams. to the premotor cortex, as the impulses responsible for tremor are ultimately transmitted by the lateral corticospinal tract. Some of what is known about the physiology of specific tremors is noted in the following paragraphs.


Neurology_Adams

Neurology_Adams. Action tremors are evident during use of the affected body part, as opposed to tremor that is apparent in a position of rest or repose. Action tremors can be roughly divided into two categories: goal directed action tremor of the ataxic type related to cerebellar disorders (discussed in Chap. 5) and postural tremors, which are either the enhanced physiologic variety or essential tremor (Fig. 4-6). A postural tremor occurs with the limbs and trunk actively maintained in certain positions (such as holding the arms outstretched) and may persist throughout active movement. More particularly, the tremor is absent when the limbs are relaxed but becomes evident when the muscles are activated. The tremor is accentuated as greater precision of movement is demanded, but it does not approach the degree of augmentation seen with cerebellar intention tremor. Most cases of action tremor are characterized by relatively rhythmic bursts of grouped motor neuron discharges that occur not quite


Neurology_Adams

Neurology_Adams. the degree of augmentation seen with cerebellar intention tremor. Most cases of action tremor are characterized by relatively rhythmic bursts of grouped motor neuron discharges that occur not quite synchronously in opposing muscle groups as shown in Fig. 4-7. Slight inequalities in the strength and timing of contraction of opposing muscle groups account for the tremor. In contrast, rest (parkinsonian) tremor, is characterized by alternating activity in agonist and antagonist muscles.


Neurology_Adams

Neurology_Adams. Enhanced physiologic tremor The type of action tremor that seems merely to be an exaggeration of the above-described physiologic tremor, can be brought out in most normal persons. It has the same fast frequency as physiologic tremor (about 10 Hz; see Fig. 4-7) but with greater amplitude. Such a tremor, best elicited by holding the arms outstretched with fingers spread apart, is characteristic of intense fright and anxiety (hyperadrenergic states), certain metabolic disturbances (hyperthyroidism, hypercortisolism, hypoglycemia), pheochromocytoma, intense physical exertion, withdrawal from alcohol and other sedative drugs, and the toxic effects of several drugs—lithium, nicotinic acid, xanthines (coffee, tea, aminophylline), cocaine, methylphenidate, other stimulant drugs, and corticosteroids. Young and colleagues have determined that the enhancement of physiologic tremor that occurs in metabolic and toxic states is not a function of the central nervous system but is instead a


Neurology_Adams

Neurology_Adams. Young and colleagues have determined that the enhancement of physiologic tremor that occurs in metabolic and toxic states is not a function of the central nervous system but is instead a consequence of stimulation of muscular beta-adrenergic receptors by increased levels of circulating catecholamines.


Neurology_Adams

Neurology_Adams. A special type of postural action tremor, closely related to the enhanced physiologic tremor, occurs as the most prominent feature of the early stages of withdrawal from alcohol or other sedative (benzodiazepines, barbiturates) following a sustained period of use. LeFebvre-D’Amour and colleagues have described two tremors of slightly different frequency, one of which is indistinguishable from essential tremor. Either of these may occur as the individual emerges from a relatively short period of intoxication (“morning shakes”). A number of alcoholics, on recovery from the withdrawal state, exhibit a persistent tremor of essential (familial) type, described below. The mechanisms involved in alcohol withdrawal symptoms are discussed in the chapter on Disorders of the Nervous System Caused by Alcohol, Drugs, Toxins, and Chemical Agents.


Neurology_Adams

Neurology_Adams. Action tremors are seen in a number of other clinical settings. A large number of drugs can cause tremor either as direct or an idiosyncratic effect. At times it is difficult to determine if the drug is simply exaggerating a preexisting tremor, but most often the tremor is only evident with the drug and ceases when the drug is withdrawn. The main examples are antiepileptic medications, particularly valproate; bronchodilators and adrenergic drugs such as aminophylline, cocaine, thyroxine; gastrointestinal drugs such as metoclopramide and cimetidine; psychiatric drugs, mainly lithium but also amitriptyline, the selective serotonin reuptake inhibitors and haloperidol; and immunosuppressants such as tamoxifen, tacrolimus, cyclosporine, and interferon-alpha. A more complete discussion of drug-induced tremors can be found in the review by Morgan and Sethi. A coarse action tremor, sometimes combined with myoclonus, accompanies various types of meningoencephalitis (e.g., in the past it was


Neurology_Adams

Neurology_Adams. tremors can be found in the review by Morgan and Sethi. A coarse action tremor, sometimes combined with myoclonus, accompanies various types of meningoencephalitis (e.g., in the past it was quite common with syphilitic general paresis) and certain intoxications (methyl bromide and bismuth).


Neurology_Adams

Neurology_Adams. This, the commonest type of tremor, is of lower frequency (4 to 8 Hz) than physiologic tremor and is unassociated with other neurologic changes; thus it is called “essential.” It is usually at the lower end of this frequency range and of variable amplitude. Aside from its rate, the identifying feature is its appearance or enhancement with attempts to maintain a static limb posture or to produce a smooth trajectory of movement. Like many other tremors, essential tremor is worsened by emotion, exercise, and fatigue. One infrequent type of essential tremor is faster and of the same frequency (6 to 8 Hz) as enhanced physiologic tremor. Essential tremor may increase in severity to a point where the patient’s handwriting becomes illegible and he cannot bring a spoon or glass to his lips without spilling its contents. Eventually, all tasks that require manual dexterity become difficult or impossible. The pathophysiology of this tremor and its treatment are discussed further on.


Neurology_Adams

Neurology_Adams. Typical essential tremor occurs in several members of a family, for which reason it has been called familial or hereditary essential tremor. Inheritance is in an autosomal dominant pattern with high penetrance. The idiopathic and familial types cannot be distinguished on the basis of their physiologic and pharmacologic properties and probably should not be considered as separate entities. This condition had been referred to as “benign essential tremor,” but this is hardly so in many patients in whom it worsens with age and interferes with normal activities.


Neurology_Adams

Neurology_Adams. Essential tremor most often makes its appearance late in the second decade, but it may begin in childhood and then persist. A second peak of increased incidence occurs in adults older than 35 years of age. It is a relatively common disorder, with an estimated prevalence of 415 per 100,000 persons older than the age of 40 years (Haerer et al). As described by Elble, the tremor frequency diminishes slightly with age while its amplitude increases. The tremor practically always begins in the hands and is said to be symmetrical; in approximately 15 percent of patients, however, it appears first in the dominant hand and an emerging concept has been that it is more often asymmetric than stated in older descriptions. It is also possible, of course, that the patient does not find a mild bilateral tremor troublesome until it affects activities that are dependent on the dominant hand. However, a severe isolated arm or leg tremor, or a predominant finger tremor, should still suggest another


Neurology_Adams

Neurology_Adams. tremor troublesome until it affects activities that are dependent on the dominant hand. However, a severe isolated arm or leg tremor, or a predominant finger tremor, should still suggest another disease (Parkinson disease or focal dystonia, as described further on).


Neurology_Adams

Neurology_Adams. The tremor may remain limited to the upper limbs or to a side-to-side or nodding movement of the head; tremor of the chin may be added or may occur independently. In certain cases of essential tremor, there is additional involvement of the jaw, lips, tongue, and larynx, the latter imparting a severe quaver to the voice (voice tremor). Infrequently, the tremor of the head or voice precedes that of the hands. The head tremor is also postural in nature and disappears when the head is supported. It has also been noted that the limb and head tremors tend to be muted when the patient walks, in contrast to most parkinsonian tremors. In some of our patients whose tremor remained isolated to the head for a decade or more, there has been little if any progression to the arms and almost no increase of the amplitude of movement.


Neurology_Adams

Neurology_Adams. The lower limbs are usually spared or only minimally affected. In the large series of familial tremor cases by Bain and colleagues, solitary jaw or head tremor was not found but we have observed isolated head tremor, as noted. Most patients with essential tremor will have identified the amplifying effects of anxiety and the ameliorating effects of alcohol on their tremor. We have also observed the tremor to become greatly exaggerated during emergence from anesthesia in a few patients.


Neurology_Adams

Neurology_Adams. Electromyographic studies reveal that the tremor is generated by more or less rhythmic and almost simultaneous bursts of activity in pairs of agonist and antagonist muscles (Fig. 4-7B). Less often, especially in the tremors at the lower range of frequency, the activity in agonist and antagonist muscles alternates (“alternate beat tremor”), a feature more characteristic of Parkinson disease, which the tremor then superficially resembles (see below). Tremor of either pattern may be disabling, but the less common, slower, alternate-beat tremor tends to be of higher amplitude, is more of a handicap, and is usually more resistant to treatment.


Neurology_Adams

Neurology_Adams. Pathophysiology To date, only a few cases of essential tremor have been examined postmortem, and these have disclosed no consistent lesion to which the tremor could indisputably be attributed (Herskovits and Blackwood; Cerosimo and Koller). A singular case of a 90-year-old woman studied by Louis and colleagues demonstrated more extensive cerebellar cortical and dentate nucleus cell loss and reactive changes than had been previously reported.


Neurology_Adams

Neurology_Adams. The question of the existence and locus of a generator for essential tremor as opposed to the unbalancing of a feedback loop system, is unresolved. As indicated by McAuley, various studies demonstrate that rhythmic tremor activity is not primarily generated in the cortex. Based on electrophysiologic recordings in patients, two likely origins of oscillatory activity are the olivocerebellar circuits and the thalamus. Whether a particular structure possesses intrinsic rhythmicity or, as currently favored, the tremor is an expression of reciprocal oscillations in circuits of the dentato–brainstem–cerebellar or thalamic–tegmental systems is not at all clear. Studies of blood flow in patients with essential tremor by Colebatch and coworkers affirm that the cerebellum is rhythmically activated; on this basis they argue that there is a release of an oscillatory mechanism in the olivocerebellar pathway. Dubinsky and Hallett demonstrated that the inferior olives also become hypermetabolic when


Neurology_Adams

Neurology_Adams. on this basis they argue that there is a release of an oscillatory mechanism in the olivocerebellar pathway. Dubinsky and Hallett demonstrated that the inferior olives also become hypermetabolic when essential tremor is activated, but this has been questioned by Wills and colleagues who recorded increased blood flow in the cerebellum and red nuclei, but not in the olive. These proposed mechanisms of tremor are reviewed by Elble and also by Hallett.


Neurology_Adams

Neurology_Adams. Although this disorder is familial, almost always autosomal dominant, a single genetic site has not yet been established; several candidate polymorphisms have been tentatively proposed.


Neurology_Adams

Neurology_Adams. Treatment A curious fact about essential tremor of the typical (non–alternate-beat) type is that it can be suppressed by a small amount of alcohol in more than 75 percent of patients; but once the effects of the alcohol have worn off, the tremor returns and may even worsen for a time. Of more therapeutic interest, essential tremor is inhibited by the beta-adrenergic antagonist propranolol (between 80 and 200 mg per day in divided doses or as a sustained-release preparation) taken orally, usually remaining effective over a long period of time. Often it takes several days or weeks for the effect to be evident. The benefit is variable and often incomplete; most studies indicate that 50 to 70 percent of patients have some symptomatic relief but may complain of side effects such as fatigue, erectile dysfunction, and bronchospasm (see Young and colleagues). Several but not all of the other beta-blocking drugs are similarly effective: metoprolol and nadolol, which may be better tolerated


Neurology_Adams

Neurology_Adams. erectile dysfunction, and bronchospasm (see Young and colleagues). Several but not all of the other beta-blocking drugs are similarly effective: metoprolol and nadolol, which may be better tolerated than propranolol, are the ones most extensively studied, but they have yielded less consistent results compared to propranolol. The relative merits of different drugs in this class are discussed by Louis and by Koller et al.


Neurology_Adams

Neurology_Adams. The mechanism and site of action of beta-blocking agents is not known with certainty. It is blockade of the beta-2 adrenergic receptor that is most closely aligned with reduction of the tremor. Young and associates have shown that neither propranolol nor ethanol, when injected intraarterially into a limb, decreases the amplitude of essential tremor. These findings, and the delay in action of medications, suggest that their therapeutic effect is due less to blockade of the peripheral beta-adrenergic receptors than to their action on structures within the central nervous system. This is in contrast to the earlier mentioned muscle receptor-mediated effect of adrenergic compounds in physiologic tremor. It is possible that ambiguity regarding the action of beta-blocking drugs is the result of their effect on physiological tremor that is superimposed on essential tremor.


Neurology_Adams

Neurology_Adams. The barbiturate drug primidone has also been effective in controlling essential tremor and may be tried in patients for whom beta-blocking medications and not effective or tolerated. The side effects may be drowsiness, nausea, and slight ataxia. Treatment should be initiated at 25 mg twice or three times per day and increased slowly in order to minimize these effects. Gabapentin, topiramate (see Connor), mirtazapine, a variety of benzodiazepines and a large number of other drugs have been used generally without success, and should be considered second-line therapies; these alternatives are discussed by Louis. Amantadine also has a modest effect on tremor and may be used as an adjunct.


Neurology_Adams

Neurology_Adams. The alternate-beat, slow, high-amplitude, kinetic-predominant type of essential tremor is more difficult to suppress but has reportedly responded to clonazepam (Biary and Koller); in our experience, however, this approach has not been as successful. Alcohol and primidone have less effect than they do in typical essential tremor. Indeed, the tremor has often been resistant to most attempts at suppression, for which reason surgical approaches are now being used (see further on).


Neurology_Adams

Neurology_Adams. Injections of botulinum toxin into a portion of a limb can reduce the severity of essential tremor locally, but the accompanying weakness of arm and hand muscles often proves unacceptable to the patient. The same medication injected into the vocal cords can suppress severe voice tremor as described in a series of cases by Adler and colleagues as well as by others, but caution must be exercised to avoid paralyzing the cords. Doses as low as 1 U of toxin injected into each cord may be effective, with a latency of several days. The long-term repeated use of this treatment has not been adequately studied for essential-type limb or voice tremor.


Neurology_Adams

Neurology_Adams. In resistant cases of essential tremor of the fast or slow variety, stimulation by electrodes implanted or ablative lesions in the ventral medial nucleus of the thalamus or the internal segment of the globus pallidus (of the same type used to treat Parkinson disease) has produced a response over many years; details can be found in the small study reported by Sydow and colleagues. Tremor of Polyneuropathy


Neurology_Adams

Neurology_Adams. Tremor of Polyneuropathy Adams and coworkers described a disabling action tremor in patients with chronic demyelinating and paraproteinemic polyneuropathies. It is a particularly prominent feature of the polyneuropathy caused by immunoglobulin M (IgM) antibodies to myelin-associated glycoprotein (MAG). The movements simulate a coarse essential, or ataxic, tremor and typically worsen if the patient is asked to hold his finger near a target. The EMG pattern is more irregular than that in essential (familial) tremor (Fig. 4-7C). Pedersen and colleagues have found it to vary greatly in amplitude with considerable side-to-side oscillation, which is induced by co-contracting muscle activity; they also found little suppression of the tremor with loading of the limb, unlike most other organic tremors. It is hypothesized that there is a disturbance of muscle spindle afferents.


Neurology_Adams

Neurology_Adams. Some cases of acute or chronic inflammatory neuropathy or ganglionopathy may be marked by a similar and prominent ataxic tremor and a faster action tremor. A special type of Guillain-Barré syndrome (Fisher variant) is characterized by a tremor that is indistinguishable from the ataxic type but probably has a peripheral basis. Also, the inherited disease, peroneal muscular atrophy (Charcot-Marie-Tooth disease), may be associated with tremor of the essential type but the two may be coincident rather than directly related; this combination of symptoms was the basis on which Roussy and Levy incorrectly set it apart as a distinct disease. Chapter 43 discusses these polyneuropathies. Parkinsonian (Repose, Rest) Tremor


Neurology_Adams

Neurology_Adams. Parkinsonian (Repose, Rest) Tremor This is a coarse, rhythmic tremor with a frequency of 3 to 5 Hz, characterized by bursts of activity that alternate between opposing muscle groups. The tremor is most often localized in one or both hands and forearms and less frequently in the feet, jaw, lips, or tongue (Fig. 4-7D). It occurs when the limb is in an attitude of repose and is suppressed or diminished by willed movement, at least momentarily, only to reassert itself once the limb assumes a new position. Even though it is termed a “resting” tremor, maintaining the arm in an attitude of repose requires a certain degree of muscular contraction, albeit slight. If the tremulous hand is completely relaxed, as it is when the arm is fully supported at the wrist and elbow, the tremor usually disappears. It is difficult, however, for the parkinsonian patient to relax and instead it is typical to maintain a state of slight tonic contraction of the trunk and proximal muscles.


Neurology_Adams

Neurology_Adams. Parkinsonian tremor is “alternating” in the sense that it takes the form of flexion–extension or abduction–adduction of the fingers or the hand; pronation–supination of the hand and forearm is also a common presentation. Flexion–extension of the fingers in combination with adduction–abduction of the thumb yields the characteristic “pill-rolling” tremor of Parkinson disease. The tremor continues and may worsen while the patient walks, unlike essential tremor; indeed, it may first become apparent to the patient during walking. When the legs are affected, the tremor takes the form of a flexion–extension movement of the foot, sometimes the knee. In the jaw and lips, it is seen as up-and-down and pursing movements, respectively. The eyelids, if they are closed lightly, tend to flutter rhythmically (blepharoclonus), and the tongue, when protruded, may move in and out of the mouth at about the same tempo as the tremor elsewhere.


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Neurology_Adams. The cogwheel effect is a ratchet-like interruption perceived by the examiner on passive movement of an extremity (the Negro sign) as mentioned earlier. It is said by many authors to be no more than a palpable tremor superimposed on rigidity and as such, is not specific for Parkinson disease although it is most often recognized in that condition. This explanation is called into question by the numerous cases in which Parkinson patients display minimal or no resting tremor but nonetheless have the cogwheel phenomenon. Cogwheeling can be brought out by having the patient engage the opposite limb, such as tracing circles in the air; called the Froment sign, this finding was originally described in essential tremor.


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Neurology_Adams. The parkinsonian tremor frequency is surprisingly constant over long periods, but the amplitude is variable. Emotional stress augments the amplitude and may add to the effects of an enhanced physiologic or essential tremor. With advance of the disease, increasing rigidity of the limbs obscures or reduces it. It is curious how little the tremor interferes with voluntary movement; for example, it is possible for a tremulous patient to raise a full glass of water to his lips and drain its contents without spilling a drop; this is not always the case with “benign” essential tremor, as already emphasized.


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Neurology_Adams. Almost always in Parkinson disease, the tremor is asymmetric and at the outset may be entirely unilateral. There is not a close correspondence between the degree of tremor and the degree of rigidity or akinesia. A bilateral parkinsonian type of tremor may also be seen in elderly persons without akinesia, rigidity, or mask-like facies. In some of these patients, the tremor is followed years later by the other manifestations of Parkinson disease, but in others it is not, remaining unchanged or progressing very slowly, unaffected by anti-Parkinson drugs. This entity probably equates with the earlier mentioned alternate-beat type of essential tremor. Patients with Wilson disease or an acquired form of hepatocerebral degeneration may also show a tremor of parkinsonian type, usually mixed with ataxic tremor and other extrapyramidal motor abnormalities. An alternating tremor may be seen in toxin and drug-induced parkinsonism but it is relatively symmetric and tends not to be a prominent


Neurology_Adams

Neurology_Adams. ataxic tremor and other extrapyramidal motor abnormalities. An alternating tremor may be seen in toxin and drug-induced parkinsonism but it is relatively symmetric and tends not to be a prominent feature. The tremor of postencephalitic parkinsonism (which is now virtually extinct) often had greater amplitude than typical parkinsonian tremor and involved proximal muscles.


Neurology_Adams

Neurology_Adams. Parkinsonian tremor is suppressed to some extent by the anticholinergic drugs benztropine and trihexyphenidyl; it is also suppressed less consistently but sometimes impressively by L-dopa and dopaminergic agonist drugs. Parkinsonian tremor is often associated with an additional tremor of faster frequency; the latter is of essential type and responds better to beta-blocking drugs than to anti-Parkinson medications. Stereotactic lesions or electrical stimulation in the basal ventrolateral nucleus of the thalamus diminishes or abolishes tremor contralaterally; other stimulation sites such as the internal segment of the globus pallidus and the subthalamic nucleus are also effective but possibly to a lesser degree. Chapter 38 discusses treatment of Parkinson disease in greater detail.


Neurology_Adams

Neurology_Adams. Pathophysiology The anatomic basis of parkinsonian tremor is not known. In Parkinson disease, the visible lesions predominate in the substantia nigra, and this was true also of the postencephalitic form of the disease. In animals, however, experimental lesions confined to the substantia nigra or striatopallidum do not result in tremor. Moreover, not all patients with lesions of the substantia nigra have tremor; in some there is only bradykinesia and rigidity. In a group of patients poisoned with the toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a meperidine analogue that destroys the neurons of the substantia nigra pars compacta, only half developed a tremor, which had more of the characteristics of a proximal action or postural tremor than of a rest tremor as discussed by Burns and colleagues. In all likelihood, these inconsistencies reflect the complex influence of dopamine on a number of basal ganglionic structures.


Neurology_Adams

Neurology_Adams. Ward and others have produced a Parkinson-like tremor in monkeys by placing a lesion in the ventromedial tegmentum of the midbrain, just caudal to the red nucleus and dorsal to the substantia nigra. He postulated that interruption of the descending fibers at this site liberates an oscillating mechanism in the lower brainstem; this presumably involves limb innervation via the reticulospinal pathway. Alternative possibilities are that the lesion in the ventromedial tegmentum interrupts the brachium conjunctivum, a tegmental-thalamic projection, or the descending limb of the superior cerebellar peduncle, which functions as a link in a dentatoreticular-cerebellar feedback mechanism (see Fig. 5-3). The differential effect of drugs on tremor and bradykinesia suggest that they must have separate mechanisms. Intention (Ataxic, Cerebellar, Goal-Directed Action) Tremor


Neurology_Adams

Neurology_Adams. As will be discussed in Chap. 5, the word intention is ambiguous in this context because the tremor itself is not intentional and occurs not when the patient intends to make a movement but only during the most demanding phases of active performance. In this sense it is a kinetic or action tremor, but the latter term has connotations of the essential tremor to neurologists, as described earlier. The term ataxic is a suitable substitute for intention, because this tremor is always combined with cerebellar ataxia and adds to it. Its salient feature is that it requires for its full expression the performance of an exacting, precise, projected movement. The tremor is absent both when the limbs are inactive and during the first part of a voluntary movement, but as the action continues and fine adjustments of the movement are demanded (e.g., in touching the tip of the nose or the examiner’s finger), an irregular interruption of forward progression appears. These side-to-side oscillations are


Neurology_Adams

Neurology_Adams. of the movement are demanded (e.g., in touching the tip of the nose or the examiner’s finger), an irregular interruption of forward progression appears. These side-to-side oscillations are more or less rhythmic and may continue for several beats after the target has been reached. Unlike essential and parkinsonian tremors, the oscillations occur in more than one plane but are mainly horizontal and perpendicular to the trajectory of movement. The tremor and ataxia may seriously interfere with the patient’s performance of skilled acts. In some patients there is a rhythmic oscillation of the head on the trunk (titubation), or of the trunk itself, at approximately the same rate. As already indicated, this type of tremor points to disease of the cerebellum or its outflow connections, but certain peripheral nerve diseases may simulate it.


Neurology_Adams

Neurology_Adams. Ataxic tremor has been produced in monkeys by inactivating the deep cerebellar nuclei or by sectioning the superior cerebellar peduncle or the brachium conjunctivum below its decussation. A lesion of the nucleus interpositus or dentate nucleus causes an ipsilateral tremor of ataxic type, as one might expect, associated with other manifestations of cerebellar ataxia. In addition, such a lesion gives rise to a “simple tremor,” which is the term that Carpenter applied to a “resting” or parkinsonian tremor. He found that the latter was most prominent during the early postoperative period and was less enduring than ataxic tremor. Nevertheless, the concurrence of the two types of tremor and the fact that both can be abolished by ablation of the contralateral ventrolateral thalamic nucleus suggest that they have related neural mechanisms, at least in monkeys.


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Neurology_Adams. There is another, higher amplitude tremor associated with cerebellar ataxia, in which every movement, even lifting the arm slightly or maintaining a static posture with the arms held out, results in a wide-ranging, rhythmic 2to 5-Hz “wing-beating” movement. This tremor can be of sufficient force to throw the patient off balance. In such cases, the lesion is usually in the midbrain, involving the rostral projections of the dentatorubrothalamic fibers and the medial part of the ventral tegmental reticular nucleus. Because of the location of the lesion in the region of the red nucleus, Holmes originally called this a rubral tremor. However, experimental evidence in monkeys indicates that the tremor is produced not by a lesion of the red nucleus per se but by interruption of fibers that traverse this nucleus—that is, the cerebellar efferent fibers that form the superior cerebellar peduncle (Carpenter). This type of tremor is seen most often in patients with multiple sclerosis or Wilson


Neurology_Adams

Neurology_Adams. this nucleus—that is, the cerebellar efferent fibers that form the superior cerebellar peduncle (Carpenter). This type of tremor is seen most often in patients with multiple sclerosis or Wilson disease, occasionally with vascular and other lesions of the tegmentum of the midbrain and subthalamus, and rarely as an effect of antipsychosis medications. Beta-adrenergic blocking agents, anticholinergic drugs, and L-dopa have little therapeutic effect. It is abolished by a surgical lesion in the opposite ventrolateral nucleus of the thalamus. Thalamic stimulation may be particularly helpful in severe cases that are the result of demyelinating lesions in the cerebellar peduncles.


Neurology_Adams

Neurology_Adams. This is a strongly familial episodic tremor disorder of the chin and lower lip that begins in childhood and may worsen with age. Psychic stress and concentration are known to precipitate the movements, which are described by Danek as “trembling.” Rare instances involve other facial muscles. The disorder must be distinguished from a similar tremor of the chin that is part of essential tremor, facial myokymia or fasciculations, and palatal tremor. The disorder results from a mutation on chromosome 9.


Neurology_Adams

Neurology_Adams. This is a rare but striking tremor isolated to the legs that is remarkable by its occurrence only during quiet standing and its cessation almost immediately on walking. It is difficult to classify and more relevant to disorders of gait than it is to tremors of other types. The frequency of the tremor has been recorded as approximately 14 to 16 Hz, making it difficult to observe and more easily palpable. An important accompanying feature is the sensation of severe imbalance, which causes the patient to assume a widened stance while standing; these patients are unable to walk a straight line (tandem gait). We have observed prominent tonic contraction of the legs during standing, seemingly in an attempt to overcome imbalance (see Heilman; Thompson, Rothwell, Day et al). The arms are affected little or not at all. Often the first step or two when the patient begins to walk are halting, but thereafter, the gait is entirely normal. Because falls are infrequent, the symptoms are often


Neurology_Adams

Neurology_Adams. little or not at all. Often the first step or two when the patient begins to walk are halting, but thereafter, the gait is entirely normal. Because falls are infrequent, the symptoms are often attributed to hysteria. Tremulousness is not present when the patient is seated or reclining, but in the latter positions it can be evoked by strong contraction of the leg muscles against resistance.


Neurology_Adams

Neurology_Adams. Electromyographic recordings demonstrate rhythmic co-contraction of the gastrocnemius and anterior tibialis muscles. Although some authors, such as Wee and colleagues, have classified the disorder as a type of essential tremor, most of its characteristics suggest otherwise. Sharott and coworkers consider it an exaggerated physiologic tremor in response to imbalance; others have suggested a spinal origin for the tremor because of an intrinsic rhythm at approximately 16 Hz that is generated by damaged spinal cord in patients with myelopathy. Some cases have responded to the administration of clonazepam, gabapentin, primidone, or sodium valproate alone or in combination but it often proves difficult to treat. A few intractable cases have been treated with an implanted spinal cord stimulator (Krauss et al, 2005).


Neurology_Adams

Neurology_Adams. Tremors may be a feature of incipient dystonia as mentioned earlier. When the underlying dystonic posturing is not overt, the tremor may be ascribed to the essential variety or to hysteria. Dystonic tremor is focal, for example superimposed on torticollis, or a dystonic hand. The movement is not entirely rhythmic, sometimes jerky, and often intermittent. These cases are also discussed further on in the section on focal dystonia. In addition, a fair number of patients with dystonia have an essential tremor.


Neurology_Adams

Neurology_Adams. Tremor may be a dramatic manifestation of hysteria. It simulates many types of organic tremor, often causing some difficulty in diagnosis. Psychogenic tremors are usually restricted to a single limb, often in the dominant hand; they are gross in nature and are less regular than the common static or action tremors. Importantly, they often diminish in amplitude or disappear if the patient is distracted as, for example, when asked to make a complex movement with the opposite hand. If the examiner restrains the affected hand and arm, the tremor may move to a more proximal part of the limb or to another part of the body (“chasing the tremor”). Other useful features in identifying hysterical tremor are paradoxical exaggeration of the tremor by loading the limb—for example, by having the patient hold a book or other heavy object—which reduces almost all other tremors with exception of those produced by polyneuropathy. Hysterical tremor often acquires the frequency of a willed movement in a


Neurology_Adams

Neurology_Adams. hold a book or other heavy object—which reduces almost all other tremors with exception of those produced by polyneuropathy. Hysterical tremor often acquires the frequency of a willed movement in a different limb.


Neurology_Adams

Neurology_Adams. Tremors of Complex Type Not all tremors correspond exactly with those described above and several of them may coexist. It is common for one type of tremor to show a feature ordinarily considered characteristic of another. In some parkinsonian patients, for example, the tremor is accentuated rather than dampened by active movement; in others, the tremor may be very mild or absent in repose and become obvious only with movement of the limbs. As mentioned above, a patient with a typical parkinsonian tremor may, in addition, show a fine essential tremor of the outstretched hands and occasionally even an element of ataxic tremor as well. In a similar way, essential or familial tremor may, in its advanced stages, assume the aspects of a cerebellar tremor. Further examples include patients with essential tremor or ataxic tremor who also display a rhythmic parkinsonian tremor in relation to sustained postures.


Neurology_Adams

Neurology_Adams. This is a rare disorder consisting of rapid, rhythmic, involuntary movements of the soft palate. For many years it was considered to be a form of uniphasic myoclonus (hence the terms palatal myoclonus and palatal nystagmus). Because of the persistent rhythmicity, it is now classified as a tremor. There are two forms of this movement, according to Deuschl and colleagues. One is essential palatal tremor that reflects the rhythmic activation of the tensor veli palatini muscles; it has no known pathologic basis. The palatal movement may impart a repetitive audible click, which ceases during sleep. The second, more common form is a symptomatic palatal tremor caused by a diverse group of brainstem lesions that interrupt the central tegmental tract(s); (Fig. 5-3). There is a latency of many months after the focal injury before the tremor becomes evident. It has been reported by Deuschl and coauthors (1990) that the experience of clicking is reported by patients with the essential, but not


Neurology_Adams

Neurology_Adams. after the focal injury before the tremor becomes evident. It has been reported by Deuschl and coauthors (1990) that the experience of clicking is reported by patients with the essential, but not the symptomatic, variety. The frequency of the tremor varies greatly between patients and tends to be higher and remain fixed in the symptomatic variety.


Neurology_Adams

Neurology_Adams. Palatal tremor, in contrast to the essential type and all other tremors, persists during sleep and is sometimes associated with pendular nystagmus that is synchronized with the palatal movements. In some cases, the pharynx as well as the facial muscles, diaphragm, vocal cords, and even the muscles of the neck and shoulders partake of the persistent rhythmic movements. A similar phenomenon, in which contraction of the masseters occurs concurrently with pendular ocular convergence, has been observed in Whipple disease (oculomasticatory myorhythmia).


Neurology_Adams

Neurology_Adams. Magnetic resonance imaging (MRI) reveals no lesions to account for essential palatal tremor; in the symptomatic form, however, there are tegmental brainstem lesions accompanied by conspicuous enlargement of the inferior olivary nucleus unilaterally or bilaterally. With unilateral palatal tremor, it is the contralateral olive that becomes enlarged. It has been proposed that the lesions in the symptomatic form interrupt the circuit (dentate nucleus–brachium conjunctivum–red nucleus-central tegmental tract–olivary nucleus–dentate nucleus) that Lapresle and Ben Hamida called the triangle of Guillain-Mollaret (see Fig. 5-3). The lesions have been vascular, neoplastic, demyelinating, or traumatic, and have been found mainly in midbrain or pontine portions of the central tegmental fasciculus.


Neurology_Adams

Neurology_Adams. The physiologic basis of palatal tremor remains conjectural. Matsuo and Ajax postulated a denervation hypersensitivity of the inferior olivary nucleus and its dentate connections, but others have suggested that the critical event is denervation not of the olive but of the nucleus ambiguus and the dorsolateral reticular formation adjacent to it. Dubinsky and colleagues have suggested that palatal tremor may be based on the same mechanism as postural tremor—that is, presumably a disinhibition and rhythmic coupling of neurons in the olive induced by a lesion of the dentato-olivary pathway.


Neurology_Adams

Neurology_Adams. The use of drugs in treating this movement disorder has met with variable success. Clonazepam (0.25 to 0.5 mg/d, increasing gradually to 3.0 to 6.0 mg/d), sodium valproate (250 mg/d, increasing to 1000 mg/d), and gabapentin (up to 2100 mg) have suppressed the movement in some cases, particularly the last of these drugs, which reportedly has had a dramatic effect in some patients. Also, tetrabenazine and haloperidol have been helpful on occasion. Selective injection of the palatal muscles with botulinum toxin, while technically demanding, affords modest relief; it is particularly helpful in eliminating the bothersome ear clicking.


Neurology_Adams

Neurology_Adams. The movement disorder known as asterixis was described by Adams and Foley in patients with hepatic encephalopathy but it occurs with a variety of systemic metabolic disorders as mentioned below. It consists of arrhythmic lapses of sustained posture that allow gravity or the inherent elasticity of muscles to produce a sudden movement, which the patient then corrects, sometimes with overshoot. Later, Leavitt and Tyler and then Young and Shahani demonstrated that the initial interruption or lapse in posture is associated with EMG silence for a period of 35 to 200 ms. By interlocking EMG and electroencephalogram (EEG) recordings, Ugawa et al found that a sharp wave, probably generated in the motor cortex, immediately precedes the period of EMG silence. This confirmed that asterixis differs physiologically from both tremor and myoclonus, with which it was formerly confused; it had incorrectly been referred to as a “negative tremor” or “negative myoclonus.”


Neurology_Adams

Neurology_Adams. Asterixis is most readily evoked by asking the patient to hold his arms outstretched with hands dorsiflexed or to dorsiflex the hands and extend the fingers while resting the forearms on the bed or the arms of a chair. Flexion movements of the hands may then occur arrhythmically once or several times a minute. The same lapses in sustained muscle contraction can be provoked in any muscle group—including, for example, the protruded tongue, the closed eyelids, or the flexed trunk muscles. Sometimes, asterixis can be elicited best by asking the patient to place his hand flat on a table and raise the index finger.


Neurology_Adams

Neurology_Adams. Asterixis was first observed in patients with hepatic encephalopathy but was later noted to occur with hypercapnia, uremia, and other metabolic and toxic encephalopathies including those caused by phenytoin and other antiepileptics, usually indicating that these drugs are present in excessive concentrations. Medications in classes other than the antiepileptics, particularly some antibiotics, cause the disorder from time to time, also usually when they are present at toxic levels.


Neurology_Adams

Neurology_Adams. Unilateral asterixis occurs in an arm and leg on the side opposite an anterior thalamic infarction or small hemorrhage, after stereotaxic thalamotomy, and with an upper midbrain lesion, usually as a transient phenomenon after stroke. In two series, Kim and Montalban and colleagues came to a similar conclusion, namely, that unilateral asterixis is usually attributable to an acute thalamic stroke on the contralateral side, but there was an interesting variety of other localizations including the frontal lobe (anterior cerebral artery infarction), midbrain, and cerebellum in a few cases each. Our experience is limited to those arising from thalamic and overlying parietal vascular lesions. Many drugs may unmask unilateral asterixis that has its basis in an underlying lesion of the anterior thalamus. Of course, an individual with a metabolic encephalopathy and a hemiparesis, new or old, will only manifest asterixis on the normal side.