Types of cerebellar damage

Cerebellar ataxia can result from damage to the cerebellum itself or the pathways to or from it. Damage can occur from a number of different causes, such as stroke, tumor, degenerative disease, trauma, or malformation. The etiology of cerebellar dysfunction is often an important consideration when determining a prognosis and developing a treatment plan. Other factors to consider include whether the cerebellar lesion is static or progressive, whether it involves only the cerebellum or multiple neural structures, and whether it was present at birth or acquired.

Cerebellar strokes are rarer than cerebral strokes but not entirely uncommon; they account for less than 5% of all strokes. These strokes can involve any of the three arteries that supply the cerebellum: the superior cerebellar artery, anterior inferior cerebellar artery, and posterior inferior cerebellar artery. Depending on the territory supplied by the damaged vessel ( Table 19.1 ), there are stereotyped patterns of cerebellar and extracerebellar motor dysfunction that results. However, there is certainly some variation in distributions from person to person. Stroke involving the superior cerebellar artery often leads to dysmetria of ipsilateral arm movements, unsteadiness in walking, dysarthric speech, and nystagmus. Stroke involving the anterior inferior cerebellar artery often causes both cerebellar and extracerebellar signs (due to involvement of the pons) including dysmetria, vestibular signs, and facial sensory loss. Finally, stroke involving the posterior inferior cerebellar artery is usually, in the long run, the most benign, although initially it often presents with vertigo, unsteadiness, walking ataxia, and nystagmus. The best predictor of recovery from cerebellar stroke is whether the deep cerebellar nuclei are involved: recovery is best when they are not damaged.

Tumors in the posterior fossa (i.e., in or near cerebellum) do occur, although they are more common in children than adults. Depending on the type and location, tumors may be treatable with surgical resection, chemotherapy, radiation therapy, or some combination of these. Children with cerebellar tumors often have a good prognosis for recovery because many of the types of tumors most common in this population are benign and can be removed. Children also typically recover very well following cerebellar damage from tumor resection and show little signs of cerebellar ataxia. Tumors in adulthood often are due to a more aggressive form of cancer and therefore may have a poorer prognosis. Second to tumor type, damage of the deep cerebellar nuclei is an important factor that predicts recovery, even more so than age.

Several neurodegenerative diseases can damage the cerebellum ( Table 19.2 ). One of the more common types of degenerative diseases is a group of hereditary, autosomal dominant diseases referred to as the spinocerebellar ataxias (SCAs). Currently, there are 46 known distinct SCAs, which are named by numbers (e.g., SCA1, SCA2). Depending on the genetic abnormality, they can cause either purely cerebellar damage or combined cerebellar and extracerebellar damage. ^, Most of the SCAs have onset in midlife and are slowly progressive, which means that children of an affected parent will likely not know if they are affected until adulthood. There are genetic tests for a subset of these diseases. Because onset of symptoms is delayed and there are no effective pharmacological treatments, genetic counseling is a must before families decide whether or not to have children undergo genetic testing. A related set of diseases are the hereditary episodic ataxias, which are rare autosomal dominant diseases. As the name implies, patients with episodic ataxia will have periods of ataxia, lasting minutes to hours, brought on by exercise, stress, or excitement. Some of the episodic ataxias respond well to medications.

Cerebellar damage can occur from other sources as well. In traumatic brain injury, damage of the cerebellum is almost always found in the presence of widespread brain damage and is seen as a predictor of poorer outcome. The cerebellum is also particularly sensitive to toxins, including certain heavy metals and alcohol. Chronic alcoholism causes cerebellar atrophy preferentially involving the anterior superior vermis. ^, The inflammatory disorder multiple sclerosis also frequently produces lesions in the cerebellum. Finally, congenital brain abnormalities such as Chiari malformation damage the cerebellum by increased pressure and mechanical deformation. Recovery from cerebellar malformation is not understood; often these children have substantial damage to the brain stem or other neural structures, which may make therapy more challenging. A more comprehensive list of the variety of types of cerebellar damage is provided in Table 19.2 .

Given the wide range of cerebellar disorders, it is useful for the clinician to categorize the damage as progressive or nonprogressive. Patients with progressive disorders, such as the SCAs, are likely to experience worsening ataxia and decreased mobility over time and will need periodic therapy over the life-span for optimal function. In contrast, those with nonprogressive disorders would not be expected to worsen and some may have the potential for substantial recovery. Note that when additional brain areas are involved, rehabilitation may be more challenging, theoretically because other compensatory brain mechanisms may be impaired. This type of information is vital for making an appropriate prognosis and developing a long-term plan of care for patients with cerebellar dysfunction.

Anatomical divisions

The cerebellum is part of the hindbrain and is positioned on the dorsal surface of the brain stem at approximately the level of the pons ( Fig. 19.1 ). It is connected to the brain stem by the superior, middle, and inferior cerebellar peduncles. The cerebellar peduncles contain all of the axons that transmit information to and from the cerebellum. The cerebellum can be anatomically divided into three lobes; the anterior, posterior, and flocculonodular lobes. The primary fissure divides the anterior and posterior lobes, and the posterolateral fissure divides the posterior and flocculonodular lobes ( Fig. 19.2 ).

The Cerebellum, Bisected Through the Midsagittal Plane.

The Cerebellum, Flattened, Showing Key Structures. (A) Different shading distinguishes the three lobes of the cerebellum. The cerebellar vermis and hemispheres are also shown. (B) Functional longitudinal cerebellar zones, distinguished by different shading, and the locations of the deep cerebellar nuclei within each zone.

Looking at a sagittal slice through the cerebellum, distinct cellular regions can be visualized. The most superficial region is the cerebellar cortex, which, unlike cerebral cortex, contains only three layers. The arrangement of cells within the cortex is strikingly uniform across all cerebellar lobes and plays a vital role in determining cerebellar function, which will be described later. Deep to the cerebellar cortex is the white matter layer, which contains the axons of Purkinje cells projecting out from cerebellar cortex and the axons of mossy and climbing fibers entering the cortex from other brain and spinal regions (see Fig. 19.1 ). The cerebellar nuclei are the output structures of the cerebellum, and they make up the deepest region. These are groups of neuronal cell bodies that receive information coming into the cerebellum from the periphery and also from the cerebellar cortex, via Purkinje cell axons. The deep nuclei are arranged in pairs, with one nucleus of each pair on each side of the cerebellum. Most medially are the fastigial nuclei, followed by the globose and emboliform nuclei and, most laterally, the broad dentate nuclei (see Fig. 19.2 ). The medial and lateral vestibular nuclei also receive inputs directly from the cerebellar flocculonodular lobe and are therefore sometimes considered an additional set of cerebellar output structures.

Functional divisions and their afferent and efferent projections

Probably the most useful way of thinking about the anatomy of the cerebellum is to divide it into distinct functional longitudinal “zones.” Each cerebellar zone consists of a region of cerebellar cortex and its own pair of deep cerebellar nuclei. Each zone also has projections to and from distinct areas of the brain and spinal cord. Thus despite the regular arrangement of cells over the entire cerebellum, each functional longitudinal zone is uniquely positioned to control certain types of movement but not others. See Table 19.3 for a summary.

TABLE 19.3

Functional Longitudinal Cerebellar Zones

 

DSCT , Dorsal spinocerebellar tract; Lat , lateral; Med , medial; Retic , reticular; Vestib , vestibular; VOR , vestibuloocular reflex; VSCT , ventral spinocerebellar tract.

The medial zone consists of the midline structure, the vermis, and the fastigial nuclei. This region of the cerebellum predominantly receives afferent information from the brain stem vestibular and reticular nuclei and the dorsal and ventral spinocerebellar pathways, which convey important information regarding the current sensorimotor state of the trunk and limbs. In turn its outputs, through the fastigial nuclei, are largely to reticular and vestibular nuclei, which will form part of the medial descending system (reticulospinal and vestibulospinal tracts), with some additional projections to the cerebral cortex via the thalamus. The medial cerebellar zone is involved in the control of posture and muscle tone, upright stance, locomotion, and gaze and other eye movements.

The intermediate zone is made up of the intermediate hemispheres and the globose and emboliform nuclei. This region also receives inputs from the dorsal and ventral spinocerebellar pathways and brain stem reticular nuclei, as well as some projections from cerebral cortex that arrive via the cerebropontocerebellar pathway. ^{, , , ,} Major projections from this cerebellar zone are to the cerebral cortex via the thalamus and to the red nucleus. ^{, ,} The intermediate zone is considered to be important in controlling coordination of agonist-antagonist muscle pairs during a variety of activities including walking and voluntary limb movements. The medial and intermediate zones of the cerebellum are collectively referred to as the spinocerebellum because these are the only cerebellar regions that receive afferents from the spinal cord.

The largest region of the cerebellum is the lateral zone, which contains the two broad lateral hemispheres and their output structure, the dentate nuclei. Afferents to the lateral zone predominantly come from the cerebrum, from a wide variety of cortical areas including motor, premotor, and prefrontal cortices, parietal somatosensory and sensory association areas, and primary visual and auditory cortices. ^, Outputs from the dentate travel mostly back to large areas of the cerebrum (through the thalamus), to many of the same areas from which afferents arrived in the cerebellum. Again, these include vast regions of sensorimotor cortices. ^, Other efferent fibers project to the red nucleus in the brain stem. The lateral cerebellar zone plays a major role in control of complex, multijoint voluntary limb movements, particularly those involving visual guidance, and for the planning of complex movements and the assessment of movement errors. Because this region of the cerebellum interacts predominantly with the cerebrum, it is also commonly called the cerebrocerebellum. It is also sometimes referred to as the neocerebellum because it is considered to have arisen fairly recently in the phylogenetic tree, being much more expansive in primates than in lower animals.

The flocculonodular lobe can be considered a fourth zone of the cerebellum. It receives afferent projections directly from the vestibular primary afferents (semicircular canals and otoliths), as well as from vestibular nuclei and visual brain regions. ^{, , , ,} Outputs from the flocculonodular lobe project directly to the medial and lateral vestibular nuclei of the brain stem, without a synapse in a deep cerebellar nucleus. ^{, ,} For this reason, these vestibular nuclei are sometimes considered an additional set of deep cerebellar nuclei. This cerebellar zone helps to control eye movements and balance. The well-known vestibuloocular reflex (VOR), which provides gaze stabilization during head turning or walking, relies upon the cerebellum for proper functioning. ^, Because of its critical ties to the vestibular system, the flocculonodular lobe is also known as the vestibulocerebellum (see Fig. 19.2 ).

Physiology of cerebellar neuronal circuits

Within a longitudinal zone, thousands of microzones may exist, each consisting of a highly organized group of connected cerebellar cortical neurons. A microcomplex is the name given to a neural circuit made up of a single microzone plus the other connected neurons with which it communicates directly. The following section provides a very brief overview of the circuits important for cerebellar function and reviews the flow of neuronal signals into and out of cerebellar microzones ( Fig. 19.3 ).

Schematic of the Major Cell Types and Their Connections Within the Cerebellum. Excitatory synapses are indicated with a triangle; inhibitory synapses with a bar. DCN , Deep cerebellar nucleus; IO , inferior olive.

(Adapted with permission from Elsevier, Ito M. Cerebellar circuitry as a neuronal machine. Prog Neurobiol. 2006;78(3-5):272-303.)

Most afferent information enters the cerebellum through one of two pathways, the mossy fiber pathway or the climbing fiber pathway. Both have important actions on cerebellar Purkinje cells. The mossy fiber pathway affects “beams” or rows of Purkinje cells oriented along the cerebellar folia. Dense mossy fiber inputs arise from a wide variety of regions, including cerebral cortex, several subcortical areas, the brain stem, and spinal cord. Mossy fibers enter the cerebellar cortex and synapse onto granule cells, whose axons ascend and branch into parallel fibers. Each parallel fiber extends long distances longitudinally and synapses onto many Purkinje cells all located along the same beam. Each parallel fiber has a relatively weak effect on single Purkinje cells, but the mass effect of many thousands of parallel fiber contacts with Purkinje cells drives the Purkinje cells to fire at high rates. In contrast, each climbing fiber arises exclusively from the inferior olive located in the brain stem and contacts only a few (approximately 1 to 10) Purkinje cells. ^{, ,} Each Purkinje cell receives information from only one climbing fiber, yet the climbing fiber’s effect on the Purkinje cell is powerful, causing large complex spikes.

The Purkinje cell provides the output for the cerebellar cortex; each Purkinje cell axon projects to one of the deep cerebellar nuclei. The mossy fiber and climbing fiber pathways affect Purkinje cells differently and are thought to transmit different types of information. Mossy fibers are active at very high rates (generating action potentials at approximately 100 Hz) and are highly modulated by various sensory stimuli and motor activity. They have been speculated to relay information related to the direction, velocity, duration, or magnitude of movements or sensory stimuli. However, climbing fibers are active at very low rates (approximately 1 to 4 Hz) and do not appear to be as strongly modulated by sensory stimuli or motor activity. ^{, ,} There is still some disagreement regarding what sort of information is encoded in the climbing fiber signals, but the frequency of discharge appears to be too low to transmit information pertaining to specific parameters of sensory or motor events. However, the role of the climbing fiber is clearly important because its firing produces large complex spikes in the Purkinje cells and can also powerfully affect subsequent Purkinje cell firing. ^, Therefore it is often considered to serve as a sort of “teaching” signal to Purkinje cells.

Theories of cerebellar function

One general theory states that a primary function of the cerebellum is in coordinating multiple limb segments to generate smooth and fluid multijoint movements. This “motor coordinator” theory has support from behavioral studies demonstrating that multijoint movements appear to be particularly impaired in patients with cerebellar lesions. Multijoint movements are inherently more complex than single joint movements because they require control of mechanical interaction torques, those occurring at one segment but caused by movement of other linked segments. This model suggests that the cerebellum predicts the mechanical interactions between segments based on a stored internal knowledge of limb dynamics and helps to generate the correct motor commands for appropriate multijoint movements.

A second popular theory is the timer hypothesis. This idea proposes that the cerebellum is the main site for the temporal representation of movements. ^, Supporters of this theory suggest that cerebellar output ultimately encodes the precise temporal sequence of muscle activation with such precision that when it is lesioned it produces obvious deficits in the spatial (e.g., movement direction and magnitude) as well as the temporal domain. Other studies have shown that individuals with cerebellar damage also have impairments in perceiving time intervals, suggesting that this could be a more general cerebellar function. ^,

A third idea is that the cerebellum acts as an internal model to allow predictive control of movement. Sensory feedback is inadequate for movements that need to be both fast and accurate: it is too slow, and as a result, motor corrections would be issued too late. Instead, the brain generates motor commands based on an internal prediction of how the command would move the body. This “feedforward” control requires stored knowledge of the body’s dynamics, the environment, and the object to be manipulated; it is learned from previous exposure. The neural representation of this knowledge is referred to as an internal model because it provides the ability to reproduce the effects of motor actions in the brain. The internal model theory for cerebellar function states that the cerebellum serves as the site of an internal model for movement. Accordingly, the incoordination of movement associated with cerebellar damage is a consequence of a disrupted internal model, which disrupts nearly all aspects of feedforward motor control. This idea is appealing because it could help to explain the wide variety of motor behaviors (e.g., reaching, standing balance, eye movements) and movement parameters (e.g., force, direction) that can be impaired following cerebellar damage. Likewise, human behavioral studies have recently pointed out that cerebellar damage is frequently associated with impaired feedforward control but relatively intact feedback mechanisms. ^,

A related theory originates from the seminal works of Marr, Albus, and Ito, in which the cerebellum was theorized to be a sort of “learning machine.” This theory was based on careful examination of the anatomy and physiology within cerebellar microcircuits and continues to provide the basis for many of the current theories of cerebellar function (i.e., those described above). Central to the idea of cerebellar involvement in learning was the discovery that Purkinje cell output can be radically altered by climbing fiber induction of long-term depression (LTD) of the parallel fiber–Purkinje cell synapse. Hence climbing fiber inputs onto Purkinje cells can be viewed as providing a unique type of teaching or error signal to the cerebellum. More recently LTD, long-term potentiation (LTP), and nonsynaptic plasticity have all been shown to exist at numerous sites within the cerebellum, both in the cortex as well as the deep cerebellar nuclei. Thus there are multiple avenues for activity-dependent plasticity to occur within the cerebellum over relatively short time scales. It is presumed that the plastic changes in cerebellar output are responsible for changing motor behavior during the process of learning new skills.

To summarize, although the precise mechanisms are still under debate, most researchers can agree upon a few central themes of cerebellar function. First, the cerebellum is an integral structure for the coordination of movements. Second, precisely timed interactions between neurons produce activity-dependent plasticity at a number of different sites within the cerebellum. Presumably, this plasticity plays a fundamental role in motor learning. Convergence of these two themes would seem to indicate that a major cerebellar function is to maintain optimal motor control through constant adaptive learning processes, so that movements are appropriately adjusted for varying environmental demands.

Dysmetria

Dysmetria specifically refers to an impaired ability to properly scale movement distance. Movements are described as either hypermetric or hypometric, referring to overshooting or undershooting of targets, respectively. Many patients with cerebellar lesions will show both forms of dysmetria even during successive movements ( Fig. 19.4 ). ^, Dysmetria can be seen in both proximal and distal joints and occurs during both single-joint and multijoint movements, although multijoint movements worsen dysmetria ( Fig. 19.5 ). ^, Slow movements tend to produce hypometria, whereas fast movements almost always bring about hypermetria. For this reason, it has been speculated that hypometria represents more of a voluntary compensation for hypermetria than a primary impairment from cerebellar damage. Sometimes large end point errors can be reduced to some degree with visual feedback, but even the corrective movements themselves are still abnormal.

Trajectories of the wrist (solid lines) and final end point positions of the tip of the index finger (filled circles) during (A) slow and accurate and (B) fast and accurate reaches from a typical nondisabled individual (left) and a subject with cerebellar damage (right) . The subject with cerebellar damage shows dysmetria and an abnormally curved wrist path. Note also the tendency for hypometria during slow movements and hypermetria during fast movements (the same control and cerebellar subjects are shown in [A] and [B]). Several reaches are overlaid for each subject. Arrow indicates the reach direction. Large open circles indicate the target locations.

(Adapted with permission from the American Physiological Society, Bastian AJ, Martin TA, Keating JG, Thach WT. Cerebellar ataxia: abnormal control of interaction torques across multiple joints. J Neurophysiol . 1996;76[1]:492–509.)

Final end point positions of the tip of the index finger (numbers, each value corresponds to a different subject) during (A) single-joint (elbow only) and (B) multijoint (combined shoulder and elbow) reaches from nondisabled (left) and cerebellar (right) subjects. Cerebellar dysmetria (both hypometria and hypermetria) is greatly exacerbated during the multijoint reaching condition. Multiple reaches are shown for all subjects. Arrow indicates the reach direction. Large open circles indicate the target locations.

(Adapted with permission from the American Physiological Society, Bastian AJ, Zackowski KM, Thach WT. Cerebellar ataxia: torque deficiency or torque mismatch between joints? J Neurophysiol . 2000;83[5]:3019–3030.)

One proposed mechanism for dysmetria is an impaired ability to predict and account for the dynamics of the limbs. In particular, patients with cerebellar lesions have been demonstrated to have a specific deficit in the ability to account for interaction torques, ^, the rotational forces that act on a limb segment when another linked limb segment is in motion. When the cerebellum is intact, the central nervous system is able to predict the effects of interactions torques and appropriately counter or exploit them so as to produce a smooth, straight, and accurate reach in a feedforward manner. When the cerebellum is damaged, an incorrect or absent accounting for interaction torques leads to an incorrect feedforward motor plan and subsequently, an uncoordinated, overly curved and hypermetric or hypometric reach that requires feedback corrections to reach the target location.

Dyssynergia

Originally, Babinski coined the term “asynergia” as a deficit in the coordination of movements of one body region or in one limb segment with movements of another. Currently, dyssynergia is used to describe impairment of multijoint movements, wherein movements of specific segments are not properly sequenced or of the proper range or direction, resulting in uncoordinated multijoint movement. As indicated earlier, it is nearly universally true that patients with significant cerebellar damage show greater impairments during multijoint movements than single-joint movements. However, it is not fully understood whether the reason for that is because the deficits of single-joint movements are compounded during a multijoint movement or because the cerebellum plays a special and unique role in multijoint control. Dyssynergia appears to be related to dysmetria and therefore is probably also related to a deficit in predicting limb dynamics.

Dysdiadochokinesia

Dysdiadochokinesia specifically refers to a deficit in the coordination between agonist-antagonist muscle pairs elicited during voluntary rapid alternating movements. It is typically tested during performance of simple, fast alternating movements such as forearm supination-pronation or hand or foot tapping. Characteristic deficits are excessive slowness along with inconsistency in the rate and range of the alternating movements, which worsen as the movement continues. Dysdiadochokinesia appears to be caused by poor regulation of the timing of cessation of agonist and the initiation of antagonist muscle activity, ^, which could be related to a deficit in predicting limb dynamics. Indeed, rapid reversals in movement are dynamically difficult to control.

Decomposition

Movement decomposition refers to the breaking down of a movement sequence or a multijoint movement into a series of separate movements, each simpler than the combined movement. An example of this is the well-known finding that patients with cerebellar damage, when asked to reach to a target in front of and above the resting arm, will often flex the shoulder first and then, while holding the shoulder fixed, extend the elbow. This approach is generally slower and will produce a more curved trajectory of the finger to the target compared with nondisabled individuals who would typically perform the shoulder flexion and elbow extension at the same time to produce a nearly straight-line finger trajectory. Most likely decomposition reflects a compensatory strategy for dealing with impaired multijoint movements than it does a primary sign of cerebellar damage. ^,

Lack of check

Lack of check, sometimes also referred to as excessive “rebound,” refers to the inability to rapidly and sufficiently halt movement of a body part after a strong isometric force, previously resisting movement of the body part, is suddenly released. Individuals without cerebellar damage can very quickly halt, or “check,” this unintended movement. Individuals with cerebellar damage, on the other hand, are known to have considerable movement in the direction opposing the previous resistance, to the point that the unchecked movement risks upright balance and/or self-injury. This phenomenon is presumed to be caused by delayed cessation of agonist and/or delayed activation of the antagonist muscles.

Cerebellar tremor

Despite being a very common neurological sign, tremor is poorly defined and not well understood. There are several different forms of tremor, many with different etiologies, only some of which are related to cerebellar dysfunction, so it is important to distinguish among them. Tremor associated with damage to the cerebellum is typically called action tremor, reflecting the fact that it is absent at rest and elicited during muscle activation, and importantly, distinguishing it from the resting tremor associated with Parkinson disease. Action tremor can be classified as postural or kinetic tremor. Postural tremor occurs in muscles maintaining a static position against gravity (e.g., holding arms out in front of the body or standing in place), whereas kinetic tremor occurs in muscles producing an active voluntary movement. Therefore the movement oscillations are most visible in the same plane as the voluntary movement. Kinetic tremor typically occurs at relatively low frequencies (∼2 to 5 Hz) and can be observed during simple non–target-directed movements such as forearm pronation and supination or foot tapping, or during targeted movements such as pointing during the finger-to-nose test. Intention tremor is a specific form of kinetic tremor, which occurs during the terminal portions of visually guided movements toward a target. It may actually represent the multiple corrective movements, driven by visual feedback, to reach the target. As such, intention tremor can be tested by repeating the test movement with eyes closed: if the tremor decreases substantially or disappears, it is intention tremor.

Classic cerebellar tremor is kinetic tremor with intention tremor at movement termination. In general, cerebellar tremor is thought to be due to an insufficient ability to anticipate the effects of movement and excessive reliance on sensory feedback loops. Cerebellar tremor is highly influenced by sensory conditions and has a strong mechanical component: it is significantly reduced during isometric conditions or when vision is removed. It also can be decreased in some patients by adding an inertial load to the limb, although that strategy may also act to increase dysmetria. There may also be a significant central component to cerebellar tremor, possibly related to influences from the thalamus or the inferior olive. ^,

Hypotonia

Hypotonia in patients with cerebellar damage was first described by Holmes. It appears to arise from decreased excitatory drive to vestibulospinal and reticulospinal pathways, two major output pathways from the cerebellar vermis and flocculonodular lobe. The hypotonia usually presents as a decrease in the extensor tone necessary for holding the body upright against gravity. In cats, lesions to either the vestibular or fastigial nuclei cause this sort of postural hypotonia. ^, More recent observations in humans indicate that hypotonia is typically most problematic in cases of severe cerebellar hypoplasias affecting the vermis, such as Joubert syndrome, or in adults during the acute stage of cerebellar injury only. In cases of adult-onset acute injury, hypotonia usually resolves naturally over time and patients recover normal passive muscle tone and normal reflexes quickly. Thus hypotonia typically presents minimal to no problems for physical function.

Imbalance

Another cardinal sign of cerebellar damage is postural instability in both static and dynamic conditions. Specifically, patients with cerebellar damage usually show increased postural sway, either excessive or diminished postural responses to perturbations, poor control of equilibrium during voluntary movements of the head, arms, or legs, and sometimes abnormal oscillations of the trunk, called titubation.

Classically, cerebellar imbalance during stance was considered to be of a similar magnitude whether or not the eyes are open (i.e., little improvement noted with visual feedback ^, and a negative Romberg test). However, more recently, investigators using posturography measures have been able to distinguish several different categories of cerebellar imbalance during quiet standing, some of which do show improvement with visual stabilization. ^, For instance, patients with cerebellar damage relatively isolated to the anterior lobe typically show increased postural sway that is of a high velocity and low amplitude and occurs mainly in the anterior-posterior dimension. These individuals also tend to have associated postural tremor and increased intersegmental movements of the head, trunk, and legs and tend to improve when allowed visual information. On the other hand, localized damage to the vestibulocerebellum more often leads to increased postural sway that consists of low-frequency and high-amplitude movements without a preferred direction and without increased intersegmental movements. These individuals typically show no improvement with visual information. Patients with damage limited to the lateral cerebellum tend to have only slight or even no postural instability at all.

Human cerebellar damage is also associated with hypermetric postural responses to surface displacements or during step initiation (i.e., dynamic instability). ^, Specifically, patients tend to produce larger than normal surface-reactive torque responses and exaggerated and prolonged muscle activity, thereby overshooting the initial posture during the return phase of the recovery from a perturbation ( Fig. 19.6 ).

Postural responses from nondisabled control and cerebellar groups (average of 10 trials from 10 subjects in each group) after backward platform translations of 15 cm/s for 6 cm. Traces show (top to bottom) electromyographic recordings from various postural muscle groups, postural sway, shear force, surface torque, and platform displacement. Filled areas indicate the first 400 ms of activation in the electromyographic traces and the active surface reactive forces in the shear force and torque traces. Postural responses of the cerebellar subjects are increased, with excessive and prolonged muscle activity (note especially the abnormal activation of flexor muscle groups), larger sway and greater torque production. ABD , Rectus abdominus; fwd , forward; GAS , gastrocnemius; HAM , biceps femoris; PAR , paraspinals; pf , plantarflexion; QUA , rectus femoris; TIB , tibialis anterior.

(Adapted with permission from the American Physiological Society, Horak FB, Diener HC. Cerebellar control of postural scaling and central set in stance. J Neurophysiol . 1994;72[2]:479–493.)

Gait ataxia

Probably the greatest complaint and the most obvious sign of cerebellar damage is gait ataxia. This abnormal pattern of walking is often described as a “drunken” gait because patients often stagger and lose balance as if intoxicated. Early work of Holmes showed that patients with cerebellar lesions have severe difficulty maintaining balance during walking, which often leads to falls, typically directed backward and toward the side of the lesion. Holmes reported specifically that walking is slowed, with steps that are short, irregular in timing, and unequal in length. The legs sometimes lift overly high during swing phase by excessive flexion at the hip and knee and then lower abruptly and with uncontrolled force. The trajectory of walking often veers erratically, and patients have difficulty with stops or turns, especially if performed quickly.

Those initial reports have been confirmed numerous times; patients with cerebellar damage walk without the consistency in timing, length, and direction of steps typical of healthy adults. ^, In some cases, gait appears wide based. There is also increased variability in both the timing and movement excursion at the hip, knee, and ankle joints, and irregularities in the resulting path of the foot during swing. Coordination between joints of one leg and between legs (intralimb and interlimb coordination) is also abnormal. ^{, ,} As an example, the timing of peak flexion at one joint with respect to other joints’ positions may be altered or inconsistent. Often decomposition is also observed between hip and knee, knee and ankle, and/or hip and ankle joints. ^,

A critical component of locomotor control is the requirement for stability and dynamic balance while maintaining forward propulsion. Thus imbalance, described earlier, is also a major contributor to many features of gait ataxia. In fact, it has been shown that patients with cerebellar damage and significant balance deficits also typically demonstrate nearly all the classic features of gait ataxia (i.e., reduced stride lengths, increased stride widths, reduced joint excursions, abnormal swing foot trajectories, increased variability in foot placement, and joint-joint decomposition). In contrast, patients with cerebellar damage and significant leg coordination deficits but minimal or no balance deficits typically have very few walking abnormalities ( Fig. 19.7 ). ^, Therefore during typical conditions of level walking, balance deficits contribute much more strongly to cerebellar gait ataxia than do leg coordination deficits.

Angular excursions at the ankle (top row) , knee (middle), and hip (bottom) during fast walking from a typical nondisabled individual (left column) , a subject with cerebellar dysfunction who has significant leg incoordination but minimal imbalance (middle) , and a subject with cerebellar dysfunction who has significant imbalance but minimal leg incoordination (right) . Several strides (from initial contact to next initial contact) are overlaid for each subject. The patient with cerebellar imbalance (shaded) shows significant evidence of gait ataxia, including reduced joint excursions, excessive stride-to-stride variability, and abnormal timing between joints, whereas the patient with cerebellar leg incoordination and no imbalance shows no evidence of gait ataxia. DF , Dorsiflexion; F , flexion; PF , plantarflexion.

(Adapted with permission from the American Physiological Society, Morton SM, Bastian AJ. Relative contributions of balance and voluntary leg-coordination deficits to cerebellar gait ataxia. J Neurophysiol . 2003;89[4]:1844–1856.)

Oculomotor deficits

Eye movements are often dramatically impaired following cerebellar damage. Saccades are often slowed and dysmetric (can be hypermetric or hypometric). Smooth pursuit may be “choppy,” referred to as saccadic pursuit, wherein the smooth tracking of a target is degraded into a series of shorter saccadic movements following behind the target. The ability to cancel, or suppress, the VOR may be impaired or absent. Finally, abnormal nystagmus may also be present. The nystagmus may occur during central gaze, or there may also be alternating nystagmus or rebound nystagmus. The most common form of nystagmus in cerebellar dysfunction is gaze-evoked nystagmus, indicating nystagmus elicited toward the end ranges of lateral and/or vertical gaze. ^,

Patients with significant oculomotor abnormalities may be referred to vestibular specialists, but these deficits should never be ignored. Impaired eye movements may have a significant negative impact on physical function. For example, impaired saccades can prevent a patient from reading and saccadic pursuit can exacerbate already poor visually guided limb movements. Perhaps most devastating, deficits related to impaired oculomotor control and vestibular reflexes often worsen dynamic balance and walking abilities.

Speech impairments

Speech production may also be impaired when the cerebellum is damaged. Classically, the speech deficit associated with cerebellar damage is referred to as “scanning speech,” although it may be more generally referred to as ataxic dysarthria. Similar to limb control deficits, the primary impairment of speech may be related to the planning and prediction of movements rather than in the execution of speech components directly. Also like limb movements, most speech impairments appear to be attributable to alterations in timing and coordination. The most consistent characteristics of ataxic dysarthria are impaired articulation (the correct pronouncement of speech sounds) and impaired prosody (the pattern of stress and intonation of certain syllables or words). Other common findings include slowed speech and either a lack of or excessive loudness variability. Traditionally, speech impairments are treated primarily by speech and language pathologists.

Impaired motor learning

A critical problem associated with cerebellar damage is impaired motor learning. In humans, the cerebellum has been linked to learning of a wide variety of motor behaviors, including recovering balance after a perturbation, ^, learning new walking patterns, ^{, ,} adjusting voluntary limb movements, ^{, ,} and eye movements. ^, The type of learning that appears most reliant on the cerebellum is associative and procedural. Specifically, the cerebellum appears to be essential for learning to adjust a motor behavior through repeated practice of, or exposure to, the behavior and using error information from one trial to improve performance on subsequent trials. It is important to note that cerebellum-dependent motor learning is driven by errors directly occurring during the movement, rather than other types of feedback, such as knowledge of results after the fact (e.g., hit or miss). Studies have suggested that the type of error that drives cerebellum-dependent learning is not the target error (i.e., “How far am I from the desired target?”) but instead what has been referred to as a sensory prediction error (i.e., “How far am I from where I predicted I would be?”). ^,

In the laboratory setting, cerebellar learning is most easily tested via motor adaptation, a form of motor learning that requires a modification of an already well-learned motor behavior for new environmental or physical demands (in contrast to learning of a completely novel skill). Adaptation is an error-driven learning process that is acquired on a time-scale of minutes or hours, as opposed to days or weeks. ^, It is an active process—movement adaptation takes trial-and-error practice of the task, where errors during one trial change movement on the subsequent trial. Storage of the adapted movement is shown by the presence of aftereffects when the new demand is removed. Specifically, aftereffects are movement errors in the opposite direction to the original errors during adaptation, and they provide strong evidence that the central nervous system adjusts the predictive control for body movements with practice. ^, Thus when the new demand is removed, a process of active “unlearning” or de-adaptation must occur to return the movement to its original form. An example of a locomotor adaptation is shown in Fig. 19.8 . In this case a walking adaptation is induced by having subjects walk on a splitbelt treadmill, where one belt is moving at twice the speed of the other, forcing the two legs to walk at different speeds. Nondisabled subjects are able to rapidly restore appropriate step length symmetry after only a few minutes walking on the splitbelt treadmill. They also appear to store the newly learned set of (predictive) motor commands, demonstrated by large negative aftereffects (step length asymmetry in the reverse direction compared to early adaptation) when the treadmill belts are initially returned to a regular (nonsplit) pattern. In contrast, individuals with cerebellar damage typically show a slower rate of adaptation, a reduced magnitude of adaptation or no adaptation at all, and small or no aftereffects. See Fig. 19.8 . All of these findings indicate a significant deficiency in the capability for motor adaptation in individuals with cerebellar damage. As indicated earlier, adaptation deficits have been demonstrated in this patient population with numerous behavioral tasks. ^{, , , , ,}

Motor adaptation of step length symmetry during walking on a splitbelt treadmill from a nondisabled individual (top) and a subject with cerebellar damage (bottom) . Each data point represents the difference in step lengths between the legs (fast minus slow) for all strides during regular walking (belts tied, speed 0.5 m/s), splitbelt adaptation walking (fast belt speed 1.0 m/s; slow belt speed 0.5 m/s), and de-adaptation walking (belts tied, speed 0.5 m/s). Perfect symmetry between legs is represented by a step length difference value of 0. Note that the splitbelt condition perturbs step length symmetry initially in both subjects. The control subject rapidly adapts the walking pattern to restore appropriate step length symmetry while walking on split belts. The cerebellar subject does not adapt. Once the belts are returned to the tied condition, the control subject shows a large negative aftereffect (i.e., perturbed step length symmetry in the reverse direction), which again is rapidly adjusted to restore near-symmetric step lengths. The cerebellar subject shows a reduced aftereffect and no de-adaptation.

(Adapted with permission from the Society for Neuroscience, Morton SM, Bastian AJ. Cerebellar contributions to locomotor adaptations during splitbelt treadmill walking. J Neurosci . 2006;26[36]:9107–9116.)

Cerebellum-dependent adaptation is not the only form of motor learning, but it is an important one for rehabilitation several reasons. First, adaptation is a highly automatic process to rapidly adjust movements for new, predictable demands (e.g., adjusting the walking pattern for snow or sand; adjusting eye movements for glasses). Individuals with impaired cerebellar adaptive learning must use other means to handle new task demands, such as conscious control strategies. This is obviously inefficient and difficult, because it means that the individuals must think much more about their movements and cannot tolerate distractions. Adaptation is also important because when it is repeated many times, it can result in more permanent storage of a movement pattern that can be called on immediately (i.e., no error-based period of adaptation required). A clear example of this is the use of new bifocal glasses. Initially, there is an adaptation process to adjust eye movements when switching between the top and bottom lenses because eye movements have to be bigger for magnified objects. Yet with repeated adaptation, the brain eventually stores two calibrations, one for viewing through the top lens and one for the bottom, that can be switched between immediately. Thus adaptation can lead to a more permanent, learned calibration that is used in specific situations. Patients with cerebellar damage will not be able to make these short-term adaptations normally, and theoretically one would expect that they will not be able to form the more permanent calibrations with repeated adaptation.

Other forms of motor learning may not depend on the cerebellum and thus may be particularly useful for rehabilitation for patients with cerebellar lesions, although this has never been formally tested. One example is use-dependent motor learning, in which a person strengthens a movement pattern with repeated practice of that same pattern. It is not clear what mechanisms subserve this form of learning, although a Hebbian-like process in the cerebral cortex seems likely (i.e., repeated use strengthens the synapses in the brain that are engaged). Another form of motor learning is reward or reinforcement learning. This may involve basal ganglia circuits to strengthen movements that are rewarded. It has not been experimentally tested whether individuals with cerebellar damage can undergo either of these other forms of learning. Yet if they can, these learning mechanisms might provide important compensatory strategies for the loss of error-dependent adaptations.

Nonmotor impairments

Within the past 25 years, researchers have exposed a possible role of the cerebellum in a number of nonmotor, cognitive behaviors. Much of the early evidence for cerebellar involvement in nonmotor tasks came from functional imaging studies showing increased activation within the cerebellum during performance of certain tasks with a predominant cognitive component, such as language processing. ^, Speculation has since risen that the cerebellum may be involved in not only language, but also working memory, learning nonmotor associations between objects, and higher-order executive functions. Loss of control over emotional behaviors and certain neurodevelopmental and neuropsychiatric disorders have also been said to be linked to cerebellar damage. ^, However, interpretation of some investigations of the relationship between the cerebellum and cognition is limited in that it is sometimes difficult to separate the cognitive and motor components of a task, particularly in imaging studies in which subjects are instructed to perform some motor task to indicate a cognitive choice. ^, Nevertheless, anatomical studies have shown clearly that the cerebellum has connections to brain areas considered relatively purely cognitive in function, suggesting that a cognitive role for the cerebellum is likely.

Clinical signs by functional division

Because of the organizational structure of the cerebellum into functional longitudinal divisions, discreet areas are associated with specific signs and symptoms. Thus depending on the location and volume of cerebellar damage, patients may have just a few or nearly all of the clinical manifestations described earlier. Patients with damage to the flocculonodular lobe or midline zone typically present with some (although usually transient) loss of postural tone, impaired upright posture and balance, gait ataxia, and oculomotor deficits. ^, On the other hand, damage to the intermediate zone often results in action tremor, dysdiadochokinesia, and dysmetria of the limbs. ^, Finally, damage to the lateral zone commonly produces dyssynergia, dysmetria, and difficulty planning complex limb movements, especially those that are visually guided. ^,

Often, however, multiple longitudinal zones are affected at the same time. For instance, the arteries supplying the cerebellum each span more than one longitudinal zone, such that a stroke involving a single cerebellar artery would be likely to cause signs and symptoms associated with more than one zone (see Table 19.3 ). Degenerative disorders affecting the cerebellum also are typically pancerebellar, affecting large regions of the cerebellum. Hence these patients will also typically present with a wide variety of signs and symptoms. A careful and thorough clinical examination is therefore a requirement before a diagnosis for physical therapy can be made in patients with cerebellar damage.