Two eminent neurologists, Joseph Babinski and Gordon Holmes, were the first to cogently analyze the disturbances of movement and posture that result from lesions of the human cerebellum. For Babinski, the essential function of the cerebellum was the orchestration of muscle synergies in the performance of voluntary movement. A loss or impairment of this function—i.e., asynergia or dyssynergia—resulted in irregularity or fragmentation of the normal motor sequences involved in any given act. This deficit, most apparent in the execution of rapidly alternating movements, was referred to by Babinski as dys- or adiadochokinesis, as discussed below in the description of ataxia. He also pointed out that this was accompanied by certain maladjustments of stance and by catalepsy (perseveration of a posture), features that have not been as appreciated by modern observers.
Holmes summarized the effects of cerebellar disease as being in the acceleration and deceleration of movement. He characterized the effects in a more fundamental way than had Babinski, describing them as defects in the rate, range, and force of movement, resulting in an undershooting or overshooting of the target. He used the term decomposition to describe the fragmentation of a smooth movement into a series of irregular, jerky components. In Holmes' view, probably incorrectly, these abnormalities were attributable to an underlying hypotonia. The terminal ("intention") tremor, and the inability to check the displacement of an outstretched limb, both of which he elegantly described, he attributed to this latter defect (see further on). Gilman and colleagues have provided evidence that more than hypotonia is involved in the tremor of cerebellar incoordination. They found that deafferentation of the forelimb of a monkey resulted in dysmetria and kinetic tremor; subsequent cerebellar ablation significantly increased both the dysmetria and tremor, indicating the presence of a mechanism as yet unidentified in addition to depression of the fusimotor efferent–spindle afferent circuit.
Parts of the hypotheses of both Babinski and Holmes have been sustained by modern physiologic and clinical studies. In an analysis of rapid (ballistic) movements, Hallett and colleagues have demonstrated that with cerebellar lesions, there is a prolongation of the interval between the commanded act and the onset of movement. More prominently, there is a derangement of the normal ballistic triphasic agonist–antagonist–agonist motor sequence, referred to in Chaps. 3 and 4. The agonist burst may be too long or too short, or it may continue into the antagonist burst, resulting in excessive agonist–antagonist cocontraction at the onset of movement. These findings may explain what was described by Babinski and Holmes as asynergia, decomposition of movement, and certainly explain dysmetria. Diener and Dichgans confirmed these fundamental abnormalities in the timing and amplitude of reciprocal inhibition and of cocontraction of agonist–antagonist muscles and remarked that these were particularly evident in pluriarticular movements.
The symptoms produced in animals by ablation of discrete anatomic or functional zones of the cerebellum bear only an imperfect relationship to the symptoms of cerebellar disease in humans. This is understandable for several reasons. Most of the lesions that occur in humans do not respect the boundaries established by experimental anatomists. Even with lesions that are more or less confined to discrete functional zones (e.g., flocculonodular lobe, anterior lobe), it is difficult to identify the resultant clinical syndromes with those produced by ablation of analogous zones in cats, dogs, and even monkeys, indicating that the functional organization of these parts varies from species to species.
Clinical observations affirm what was stated above—that lesions of the cerebellum in humans give rise to the following abnormalities: (1) incoordination (ataxia) of volitional movement; (2) a characteristic tremor ("intention", or ataxic tremor, by which is meant a side-to-side oscillation as movement approaches a target), described in detail in Chap. 6; (3) disorders of equilibrium and gait; and (4) diminished muscle tone, particularly with acute lesions. Dysarthria, a common feature of cerebellar disease, is probably predicated on a similar incoordination of the muscles of articulation. In addition, the stability of conjugate eye movements is affected, giving rise to nystagmus.
Extensive lesions of one cerebellar hemisphere, especially of the anterior lobe, cause mild hypotonia, postural abnormalities, ataxia, and a mild weakness of the ipsilateral arm and leg perceived by the patient. Lesions of the deep nuclei and cerebellar peduncles have the same effects as extensive hemispheral lesions. If the lesion involves a limited portion of the cerebellar cortex and subcortical white matter, there may be surprisingly little disturbance of function, or the abnormality may be greatly attenuated with the passage of time. For example, a congenital developmental defect or an early life sclerotic cortical atrophy of half of the cerebellum may produce no clinical abnormalities. Lesions involving the superior cerebellar peduncle or the dentate nucleus cause the most severe and enduring cerebellar symptoms, which manifest mostly as ataxia in the ipsilateral limbs. Disorders of stance and gait depend more on vermian than on hemispheral or peduncular involvement. Damage in the inferior cerebellum causes vestibulocerebellar symptoms—namely, dizziness, vertigo, vomiting, and nystagmus—in varying proportions. These symptoms often share with disturbances of the vestibular system the feature of worsening with changes in head position.
The most prominent manifestations of cerebellar disease, namely, the abnormalities of intended (volitional) movement, are classified under the general heading of cerebellar incoordination or ataxia. Following Babinski, the terms dyssynergia, dysmetria, and dysdiadochokinesis came into common usage to describe cerebellar abnormalities of movement. Holmes's characterization of abnormalities in the rate, range, and force of movement is less confusing, as becomes apparent from an analysis of even simple movements. These abnormalities are brought out by standard neurologic tests, finger-to-nose and toe-to-finger movement, running the heel down the opposite shin, or tracing a square in the air with a hand or foot. In performing these tests, the patient should be asked to move the limb to the target accurately and rapidly.
The speed of initiating movement is slowed somewhat in cerebellar disease. In a detailed electrophysiologic analysis of this defect mentioned earlier, Hallett and colleagues noted, in both slow and fast movements, that the initial agonist burst was prolonged and the peak force of the agonist contraction was reduced. Also, there is irregularity and slowing of the movement itself, in both acceleration and deceleration. These abnormalities are particularly prominent as the finger or toe approaches its target. All of the foregoing defects in volitional movement are evident in acts that require alternation or rapid change in direction of movement, such as pronation–supination of the forearm or successive touching of each fingertip to the thumb. The normal rhythm of these movements is interrupted by irregularities of force and speed. Even a simple movement may be fragmented ("decomposition" of movement), each component being effected with greater or lesser force than is required. These movement abnormalities together impart a highly characteristic clumsiness to the cerebellar syndromes, an appearance that is not simulated by the weakness of upper or lower motor neuron disorders or by diseases of the basal ganglia.
Normally, deceleration of movement is smooth and accurate, even if sharp changes in the direction of a limb are demanded, as in following a moving target. With cerebellar disease, the velocity and force of the movement are not checked in the normal manner. The excursion of the limb may be arrested prematurely, and the target is then reached by a series of jerky movements. Or the limb overshoots the mark (hypermetria) because of delayed activation and diminished contraction of antagonist muscles; then the error is corrected by a series of secondary movements in which the finger or toe sways around the target before coming to rest, or moves from side to side a few times on the target itself. This side-to-side movement of the finger as it approaches its mark tends to assume a rhythmic quality; it has traditionally been referred to as intention tremor, or ataxic tremor. The tremor is mainly perpendicular to the trajectory of movement and mostly in the horizontal plane (the reason for the latter is not known). The term "intention" as applied to cerebellar tremor, while embedded in neurologic parlance, does not fully capture the necessity for the limb to be in action rather than for the patient to "intend" a movement for the tremor to be manifest. "Action tremor," however, has been used for an entirely different category of oscillations, as discussed in Chap. 6 so that simply "ataxic tremor" or "goal directed action tremor" may be preferable terms.
In addition to intention tremor, there may be a coarse, irregular, wide-range tremor that may be present in a position of repose and enhanced whenever the patient activates limb muscles, either to sustain a posture or to effect a movement. It is elicited by having the patient hold the arms out to the sides with elbows bent ("wing-beating tremor"). Holmes called it rubral tremor, and although the red nucleus may be the site of the lesion, the nucleus itself is not necessarily involved in this type of tremor. Instead, it is a result of interruption of the fibers of the superior cerebellar peduncle, which traverse the nucleus, for which reason it may be more properly called "cerebellar outflow tremor." Also, with certain sustained postures (e.g., with arms extended and hands on knees), the patient with cerebellar disease may develop a rhythmic oscillation of the fingers having much the same tempo as a parkinsonian tremor. A rhythmic tremor of the head or upper trunk (3 to 4 per second) called titubation, mainly in the anteroposterior plane, often accompanies midline cerebellar disease, but may also be a manifestation of essential tremor (see further on).
Cerebellar lesions commonly give rise to a disorder of speech, which may take one of two forms, either a slow, slurring dysarthria, like that following interruption of the corticobulbar tracts, or a scanning dysarthria with variable intonation, so called because words are broken up into syllables, as when a line of poetry is scanned for meter. The latter disorder is uniquely cerebellar; in addition to its scanning quality, speech is slow, and each syllable, after an involuntary interruption, may be uttered with less force or more force ("explosive speech") than is natural. Urban and associates deduced from cases of cerebellar infarction that the articulatory muscles are controlled from the rostral paravermian area of the anterior lobe, and this area is affected in most cases with dysarthria.
Cerebellar Eye Movement Abnormalities
Ocular movement may be altered as a result of cerebellar disease, specifically if vestibular connections are involved. Patients with cerebellar lesions are unable to hold eccentric positions of gaze, resulting in a special type of nystagmus and the need to make rapid repetitive saccades to look eccentrically. Conjugate voluntary gaze can be accomplished only by a series of jerky movements. Smooth pursuit movements are slower than normal and require that the patient make small "catch-up" saccades in an attempt to keep the moving target near the fovea. On attempted refixation to a target, the eyes overshoot the target and then oscillate through several corrective cycles until precise fixation is attained. It will be recognized that these nystagmoid abnormalities, as well as those of speech, resemble the abnormalities of volitional ataxic movements of the limbs. Currently it is considered that nystagmus caused by cerebellar disease depends on lesions of the vestibulocerebellum (Thach and Montgomery). Skew deviation (vertical displacement of one eye), vertical nystagmus, ocular flutter, and ocular myoclonus (opsoclonus) may also be the result of cerebellar disease; these abnormalities and other effects of cerebellar lesions on ocular movement are discussed in Chap. 14.
Disorders of Equilibrium and Gait
The patient with cerebellar disease has variable degrees of difficulty in standing and walking, as described more fully in Chap. 7. Standing with feet together may be impossible or maintained only briefly before the patient pitches to one side or backward. Closing the eyes may worsen this difficulty slightly, but the Romberg sign (which signifies impaired proprioceptive input) is absent if the patient is allowed to steady himself before closing his eyes. In walking, the patient's steps are uneven and placement of the foot is misaligned, resulting in unexpected lurching.
Data from patients in whom accurate clinicoanatomic correlations can be made, indicate that the disequilibrium syndrome, with normal movements of the limbs, corresponds more closely with lesions of the anterior vermis than with those of the flocculus and nodulus. This conclusion is based in part on the study of a highly stereotyped form of cerebellar degeneration in alcoholics (Chap. 42). In such patients the cerebellar disturbance is often limited to one of stance and gait, in which case the pathologic changes are restricted to the anterior parts of the superior vermis. In more severely affected patients, in whom there is also incoordination of individual movements of the limbs, the changes are found to extend laterally from the vermis, involving the anterior portions of the anterior lobes (in patients with ataxia of the legs) and the more posterior portions of the anterior lobes (in patients whose arms are affected).
Similar clinicopathologic relationships pertain in patients with familial forms of pure cerebellar cortical degeneration. In both the alcoholic and familial degenerative cases, despite a serious disturbance of stance and gait, the flocculonodular lobe may be spared completely. In other diseases, however, involvement of the posterior vermis and its connections with the pontine and mesencephalic reticular formations has caused abnormalities of ocular movement in addition to a gait disorder (see Chap. 14).
Thus the evidence that flocculonodular lesions in humans cause a disturbance of equilibrium is not conclusive. It rests on the observation that with certain tumors of childhood, namely, medulloblastomas, there may be an unsteadiness of stance and gait but no tremor or incoordination of the limbs. Insofar as these tumors are thought to originate from cell rests in the posterior medullary velum, at the base of the nodulus, it has been inferred that the disturbance of equilibrium results from involvement of this portion of the cerebellum. However, the validity of this deduction remains to be proved. By the time such tumors are imaged or viewed at operation or autopsy, they have spread beyond the confines of the nodulus, and strict clinicopathologic correlations are not possible.
The point to be made is that midline anterior cerebellar lesions may produce solely a disorder of stance and gait, i.e., nystagmus, dysarthria, and limb ataxia are absent, so that the entire problem may be missed if the patient is not observed while standing and walking.
This refers to a decrease in the normal resistance that is offered by muscles to passive manipulation (e.g., flexion and extension of a limb); it is the least evident of the cerebellar abnormalities but may explain certain clinical features not otherwise derived from the above deficits. It is related to a depression of gamma and alpha motor neuron activity, as discussed in Chap. 3. Experimentally, in cats and monkeys, acute cerebellar lesions and hypotonia are associated with a depression of fusimotor efferent and spindle afferent activity. With the passage of time, fusimotor activity is restored as hypotonia disappears (Gilman et al). As indicated earlier, Holmes believed that hypotonia was a fundamental defect in cerebellar disease, accounting not only for the defects in postural fixation (see below) but also for certain elements of ataxia and the tremor.
Hypotonia is much more apparent with acute than with chronic lesions and may be demonstrated in a number of ways. A conventional test for hypotonia is to tap the wrists of the outstretched arms, in which case the affected limb (or both limbs in diffuse cerebellar disease) will be displaced through a wider range than normal and may oscillate; this is the result of a failure of the hypotonic muscles to fixate the arm at the shoulder. When an affected limb is shaken, the flapping movements of the hand are of wider excursion than normal. If the patient places his elbows on the table with the arms flexed and the hands are allowed to hang limply, the hand of the hypotonic limb will sag. If the standing patient is rotated briefly to and fro at the shoulders, the hypotonic arm will be seen to continue to swing after the other has come to rest. Babinski also was impressed with gross alterations of posture, apparently related to hypotonia. These take the form of passive extension of the neck and involuntary bending of the knees, which are apparent when the patient is lifted from a bed or chair or upon first standing, or slumping of the shoulder on the affected side.
Failure to check a movement is a closely related phenomenon. Thus, after strongly flexing one arm against a resistance that is suddenly released, the patient may be unable to check the flexion movement, to the point where the arm may strike the face. This is the result of a delay in contraction of the triceps muscle, which ordinarily would arrest overflexion of the arm. This abnormality, incorrectly referred to as Holmes' rebound phenomenon, is more appropriately designated as an impairment of the check reflex. Stewart and Holmes, who first described this test, made the point that when resistance to flexion is suddenly removed, the normal limb moves only a short distance in flexion and then recoils very briefly in the opposite direction; in this sense, rebound of the limb is actually deficient in cerebellar disease.
Patients with these various abnormalities of tone may show little or no impairment of motor power, indicating that the maintenance of posture involves more than the voluntary contraction of muscles. It is noteworthy that the signs of cerebellar dysfunction (dysmetria, clumsiness, tremor) are absent in the hypotonic muscles of peripheral nerve disease—indicating that the cerebellum exerts a unique modulating effect on movement that is not explained by loss of tone.
Other Symptoms of Cerebellar Disease
It has been stated by some authors, not in accord with our experience, that there is a slight loss of muscular power and fatigability of muscle with acute cerebellar lesions. Insofar as these symptoms cannot be explained by other disturbances of motor function, they may be regarded as primary manifestations of cerebellar disease, but they are never severe or persistent and are of little clinical importance; anything approaching a hemiparesis in distribution or severity is not attributable to cerebellar disease.
Myoclonic movements—i.e., brief (50- to 100-ms), random contractions of muscles or groups of muscles—are, in some disease processes, combined with cerebellar ataxia. When multiple myoclonic jerks mar a volitional movement, they may be mistaken for an ataxic tremor. Action myoclonus may be the principal residual sign of hypoxic encephalopathy, as described in the discussion of postanoxic intention, or action myoclonus, in Chap. 40, and it has been proposed that this condition has a cerebellar origin. Myoclonus is described more fully in Chap. 6, where it is pointed out that it more often has its origin in diseases of the cerebral cortex.
More recently uncovered is the participation of the cerebellum in certain aspects of cognitive function and behavior (see the reviews by Leiner et al and by Schmahmann and Sherman). These authors and others have described a wide range of subtle alterations of memory and cognition, language function, and behavior in patients with disease apparently limited to the cerebellum (as determined by CT and MRI imaging). It is true that cerebellar lesions interfere with the establishment of conditioned reflexes and perhaps some deterioration in certain learning tasks as detected by specialized tests. However, it is not entirely clear if there is a uniform clinical pathologic syndrome in which a distinctive cognitive–behavioral deficit or group of deficits are related to a cerebellar disease or individual lesions. It seems to the current authors that recent investigations into the cerebral influences of the cerebellum are accurate and novel contributions to neurology, but at the same time, the changes referred to are subtle and often inapparent in the bedside neurologic examination. Rarely, as in a patient under our care, a fairly obvious aphasia from a prior insult to the cerebrum can be unmasked by an acute cerebellar lesion, such as a stroke. Slowly developing cerebellar disorders, such as tumors, do not appear to demonstrate this phenomenon.
Differential Diagnosis of Ataxia
In the diagnosis of disorders characterized by generalized cerebellar ataxia (affecting limbs, gait, and speech), the mode of onset, rate of development, and degree of permanence of the ataxia are of particular importance, as summarized in Table 5-1. Each of the major causes is discussed in an appropriate chapter. In adults, paraneoplastic and demyelinating cases account for the largest proportion of cases of subacute onset, and hereditary forms are the usual cause of very slowly progressive and chronic ones, particularly if gait is predominantly affected. The last category of genetic ataxias constitutes a large and heterogeneous group for which the mutation has been established in many cases; they are described in Chap. 39.
Table 5–1 Diagnosis of Cerebellar Ataxia ||Download (.pdf)
Table 5–1 Diagnosis of Cerebellar Ataxia
MODE OF DEVELOPMENT
Intoxication with alcohol, lithium, barbiturate, phenytoin or other antiepileptics (associated with dysarthria, nystagmus; Chaps. 42 and 43)
Diamox-responsive episodic ataxia (Chap. 37)
Childhood hyperammonemias (Chap. 37)
Acute and usually reversible
Postinfectious, with inflammatory changes in CSF (Chap. 36)
Viral cerebellar encephalitis (Chap. 33)
Extreme hyperthermia with coma at onset (Chap. 17)
Intoxication with mercury compounds or toluene (glue sniffing; spray painting; Chap. 43)
Postanoxic with intention myoclonus
Adulterated heroin ("chasing the dragon")
Subacute (over weeks)
Brain tumors such as medulloblastoma, astrocytoma, hemangioblastoma metastasis (usually with headache and papilledema; Chap. 31)
Alcoholic–nutritional (Chaps. 41 and 42)
Paraneoplastic cerebellar degeneration (Chap. 31)
Creutzfeldt-Jakob (prion) disease (Chap. 33)
Cerebellar abscess (Chap. 32)
Whipple disease (characteristically with myoclonus and oculomasticatory movements)
Sprue (gluten enteropathy)
Chronic (months to years)
Friedreich ataxia and other spinocerebellar degenerations; other hereditary cerebellar degenerations (olivopontocerebellar degenerations; cerebellar cortical degenerations [Chap. 39])
Adult form of fragile X premutation syndrome (Chaps. 38 and 39)
Hereditary metabolic diseases, often with myoclonus (Chap. 37)
Childhood ataxias, including ataxia telangiectasia, cerebellar agenesis
Unilateral ataxia without accompanying signs is most often caused by infarction or tumor in the ipsilateral cerebellar hemisphere or by demyelinating disease affecting cerebellar connections to the brainstem.
The ataxia of severe sensory neuropathy and of posterior column or posterior spinal root disease (sensory ataxia) simulates cerebellar ataxia; presumably this is a result of involvement of the large peripheral spinocerebellar afferent fibers. Tabes dorsalis and sensory ganglionopathy are prime examples of this type of disorder. However, there should seldom be difficulty in separating the two if one takes note of the loss of distal joint position sense, absence of associated cerebellar signs such as dysarthria or nystagmus, loss of tendon reflexes, and the corrective effects of vision on sensory ataxia. In peripheral neuropathy and in spinal cord disease with ataxia, the Romberg sign is invariably present, reflecting a parallel dysfunction of large afferent fibers in the posterior columns; this sign is not found in lesions of the cerebellar hemispheres except that the patient may initially sway with eyes open and a bit more with eyes closed. A cerebellar type of tremor reaches an extreme form in the large-fiber polyneuropathy related to antibodies against myelin-associated glycoprotein but the features are closer to an enhanced action tremor, as discussed in the next chapter and in Chap. 46. In the Miller Fisher syndrome, which is considered to be a version of acute Guillain-Barré polyneuropathy, sensation is intact or affected only slightly and the severe ataxia and intention tremor are presumably a result of a highly selective peripheral disorder of spinocerebellar nerve fibers. Disorders of these same fibers in the spinocerebellar tracts of the cord may produce the same sensory-ataxic effects; subacute compressive lesions such as thoracic meningioma or demyelinating lesions are the usual causes. Again, there is a prominent Romberg sign. Occasionally, a cerebellar-like tremor in one limb results from a lesion in the dorsolateral cord that interrupts afferent fibers, presumably those directed to the spinocerebellar tracts.
Vertiginous ataxia is almost solely an ataxia of gait and is distinguished by the obvious complaint of vertigo and listing to one side, past pointing, and torsional-rotatory nystagmus, as discussed in Chap. 15. The nonvertiginous ataxia of gait caused by vestibular paresis (e.g., streptomycin toxicity) has special qualities, which are described in Chap. 7. Vertigo and cerebellar ataxia may be concurrent, as in some patients with a paraneoplastic disease and in those with infarction of the lateral medulla and inferior cerebellum. An unusual and transient ataxia of the contralateral limbs occurs acutely after infarction or hemorrhage in the anterior thalamus (thalamic ataxia); in addition to characteristic signs of thalamic damage, there may be an accompanying unilateral asterixis. Finally, a lesion of the superior parietal lobule (areas 5 and 7 of Brodmann) rarely results in a similar ataxia of the contralateral limbs.