Rev. 2008; originally published 2000
Thomas O. Crawford
The Neurology of Ataxia Telangiectasia
The neurology of A-T is incredibly complicated. Those who have the disease, family members, therapists, and neurologists who are trying to figure it out keep finding things that mystify. All of us have asked, “If that isn’t possible, how is this possible?” Because the neurologic impairments of A-T are many and varied, and because many parts of the brain work quite normally, individuals with A-T and their families figure out clever ways to work around the impediments. This is an ongoing process that occurs quite naturally and unconsciously, but is also the basis of developing more effective therapies. The following is a discussion of the most important and distinctive impairments in A-T.
Ataxia refers to a loss of motor coordination. Neurologists use the word ataxia to describe a specific kind of clumsiness that arises from damage to the sensory nerves, the back part of the spinal cord, or the cerebellum, the part of the brain that controls movement. Ataxia may result from many different forms of disease, including toxins (e.g. alcohol), infections (e.g. syphilis), tumors of the spinal cord or cerebellum, diseases of the peripheral sensory nerves, and a large number of rare, hereditary disorders. The ataxia of A-T has many features that suggest there is a problem with the cerebellum. In the early 1960s, Boder and Sedgwick found that patients with A-T had conspicuous abnormalities of the cerebellum at autopsy. On the basis of these observations, they named the disease after what they thought were its most prominent features. The name A-T has proven to be a helpful label for doctors, but it may also be responsible for some misunderstanding of the disease. While many of the neurologic abnormalities are due to cerebellar damage, some problems may be caused by damage to other areas of the brain.
Some Preliminaries: Neuroanatomy
The brain is that portion of the central nervous system that is inside the skull. It is made up of three large divisions – two cerebral hemispheres, the cerebellum and the brainstem.
The cerebral hemispheres are the largest portion of the brain in humans. The cortex is the wrinkled surface of the hemispheres. This is where thinking, much of the final processing of peripheral sensation (e.g. vision, hearing, touch) and some of the control of movement (particularly the face and hands) take place. Deep in the center of the hemispheres are the basal ganglia, a group of structures that help control movement, particularly in the planning stages. Well-known diseases of the basal ganglia include Parkinson’s disease and Huntington’s disease. Abnormalities in the basal ganglia often produce problems with control of muscle tone and movement in a manner that neurologists call “extrapyramidal.” These tone and movement problems include rigidity of the limbs, abnormal extra movements and tremor (a regular involuntary shaking of the limb or body part).
The brainstem is a much smaller structure that connects the hemispheres to the body. It is extremely important because it is where many automatic functions are controlled. These include unconscious breathing, adjustment of heart rate, control of sleep and wakefulness, and a number of reflexes like swallowing and gagging, cough, balance, and final control of eye movements.
The cerebellum is the structure that sits over the back of the brainstem. We know less about specific cerebellar functions than we know about the brainstem and cerebral hemispheres. However, we do know that the cerebellum is important in learning and reliable performance of skilled repetitive movements like throwing a ball or completing a special learned dance step.
More recently there has been evidence that the cerebellum has a supportive role in a wide range of nonverbal, unconscious learning tasks, as for example blinking in response to a sound when that sound becomes associated with a puff of air to the eye. Damage to the cerebellum produces “cerebellar ataxia” that is characterized by a number of distinctive features. One well known example of cerebellar ataxia is the abnormal speech, balance and movement that arises from alcohol intoxication, or drunkenness.
General Issues about the Neurology of A-T
A-T is similar and yet different from other disorders involving the cerebellum. Both A-T and classic cerebellar diseases share the common characteristic of abnormal control of coordinated movement. In some ways, however, patients with A-T appear to have relatively preserved cerebellar functions, at least through the first decade or more. At the same time, there are prominent abnormalities of eye movement, posture, gait, movement and speech which are different from those seen with pure cerebellar damage. Each of these features will be reviewed.
It is important to note that A-T does not affect the whole brain. Some areas of the brain are particularly vulnerable in A-T, but other areas function normally for decades in most or all patients. Some of the brain systems that appear to be particularly resistant to damage include the early stages of vision in the retina and brain; hearing at all levels of processing; balance (This is different from posture as described below); the final stages of eye movements (described below); and in many patients, the cortical functions which enable comprehension of social interactions and orientation to time, place and purpose. This selective brain impairment is puzzling because the ATM protein is produced in all brain cells. An understanding of why the loss of ATM is critical to normal function in some areas but not all areas may help us to understand how the loss of ATM harms the brain. That understanding may in turn lead to development of treatments that will minimize the harm.
Another important feature of A-T is that individual patients differ in the severity of the different neurologic impairments. While the nature of each impairment is often quite distinctive (discussed below), children differ from one another in how much each impairment is present at a given age. The figure illustrates the different “shape” of the neurologic impairment in seven patients with A-T who are approximately the same age. For example, a child may have severe problems with feeding and swallowing while having less impairment of gait. Another child may have noticeable difficulty with head control, whereas the third may have the greatest impairment of gait. Despite this overall variability among different children, when siblings have A-T, the profiles of their neurologic impairments tend to be similar in “shape.”
Specific Areas of Impairment
Posture, gait, tone and movement
Children with A-T often adopt unusual postures with the head or trunk. The head will sway to an extreme lateral, forward or backward position, and stay in this position for up to half a minute before correcting, often to a different off-center position. The same postural abnormality can be seen with the trunk when in a sitting position. Here the limit is at the margin of stability, has arms and legs are extended on the opposite side to avoid toppling over. One father described, “For a kid with ataxia, he has the best balance!” Some children with A-T never develop this posture, however when it is present, it occurs only in younger children. In contrast, older children and young adults have increased tone or stiffness of the trunk and neck. It is not clear if this unusual postural problem disappears because it improves, or because it is replaced by the increase in truncal tone.
One of the features that distinguishes A-T from Friedreich’s ataxia (the most common genetic ataxia of children) is the ability to know where the limb and trunk are located in space without looking at them. At early stages of that disease, children with Friedreich’s ataxia are often able to stand squarely “at attention” without movement. Once their eyes close, however, they sway and lose their balance. This is quite different than children with A-T who often “wobble” from their earliest days of standing but do not become more unstable when their eyes close. Friedreich’s is a disorder of the peripheral nerves that leads to loss of proprioception (the ability to feel where a limb is located in space) as well as a disorder of the cerebellum. Until relatively late in the disease, proprioception is good in individuals with A-T.
The gait in A-T is often distinctive. Children typically walk with their feet inappropriately close to each other and they tend to cross their feet. They often prefer to walk quickly or run, and may sometimes walk while leaning forward over the toes. It is most curious that the greatest instability is while standing or walking very slowly. With increasing speed, the gait becomes more regular and often more reliable. Of course, the advantage of increasing stability with speed is balanced by the increasing consequences of error. A fall from a standing position is usually harmless, while a fall while running is more likely to hurt. Children with A-T will constantly strategize about walking, figuring out the best compromise between risk (the pain of falling while walking quickly or running) and the greater feeling of instability when walking slowly.
There are other gait features that distinguish A-T from other cerebellar disorders. Generally with cerebellar dysfunction, individuals compensate by widening their stance to maintain stability (hence the policeman’s instruction to stand and walk on a line when testing for drunkenness). Despite the reasonableness of this strategy, individuals with A-T seem not to be able to widen their stance or gait. In fact, in A-T the most frequent gait error is excessive narrowness of the legs (adduction), leading either to one foot catching on the other leg while it swings to the next step, or placing the foot so far over the midline that the child stumbles to the outside of the step.
Individuals with A-T and those with other cerebellar disorders differ in muscle tone. Tone is the word given to describe the amount of stiffness in a muscle when it is not purposefully activated to move. It is assessed at rest, during activation of other muscles in the body, or during automatic movements such as walking. Many disorders of the cerebellum cause decreased tone. For example, if there has been physical damage to the cerebellum, a dangling leg while sitting on a high seat will swing back and forth excessively once set in motion. In contrast, individuals with A-T generally have normal or increased tone. This increase is of a type called rigidity by neurologists. Rigidity is often seen in the head and trunk of older children and young adults with A-T. It can often be increased by activation, for example by requiring strenuous mental effort on a problem, or while concentrating on a difficult movement in the opposite arm or leg.
Extra movements of the limbs where no movement is intended are called adventitious movements. These are among the most difficult movements to categorize, as they can differ between people with the same disease or vary in the same person with a disease at different times. Many of the movements in A-T, which occur either at rest or with some activation such as holding the arms forward and outstretched, can be considered a form of chorea (irregular sudden involuntary movements) or athetosis (constant, slow writhing involuntary movements). Most children with A-T have at minimum a case of the “fidgets,” with small, irregular movements of the hands and feet while trying to lie still. Extra movements of the hands while sitting quietly become more obvious in later childhood. In older patients, some extra movements of the limbs or trunk can become the most troubling feature of A-T, because they are increased by the intent to do something. The intended task is often quite specific, such as trying to bring a spoon to mouth or writing with (but not just holding) a pen. These abnormal movements are called an “intention tremor” if rhythmic, or “intention myoclonus” if it involves an irregular unpredictable jerk. In some cases, extra movements can be so marked that they make skilled movements impossible.
(See Chapter 9 for discussion of vision and the eye itself, focusing of the lens, and movement of the eyes together to look at a very near object.)
Sedgwick and Boder, described a “peculiarity of eye movements” as one of the distinctive features diagnostic of A-T. Neurologists carefully study eye movements, because the circuits for the three main control systems are well known and are located at many important places in the brain. It is often possible to make conclusions about different problems in the brain from analyzing eye movements. (The poets call the eye a “window on the soul,” but the more prosaic neurologists think of eye movements as a “window to the brain.”)
There are three different neurologic systems that control horizontal movement of the eyes. Two of these are switched on and off, toggled from one system to another, by our attention to what we are seeing. The third is active all the time, controlled by the balance organ in the ear. All three systems act upon a central switching center for lateral eye movements in the brainstem. This center coordinates control over the neurons that signal the individual eye movement muscles.
Saccades: The first system that is controlled by our visual attention directs the eye movements known as saccades. Saccades are the fast jump of eyes from one visual target to another. When we choose to look at something new, changing our attention from one object to another, the shift in our attention drives a saccade that shifts the eyes to the new object. Each saccade has three characteristics that can be measured precisely (and we cannot change these by thinking about them). First, there is a fixed amount of time between the shift of attention and the shift of our eyes. Second, the accuracy of the eye shift is controlled. In normal circumstances, the eyes jump to the new target quite well. If the shift is too short, undershooting the target, the saccade is said to be hypometric; if the eye jumps past the new object, the saccade is hypermetric. Finally, once the saccade has started, the speed of the eye movement is very consistent.
Pursuit: The other system that is controlled by our visual attention is the pursuit. While we watch an object, if it moves a bit, our eyes will automatically track the movement of the object with a corresponding shift of eye position. Pursuit is hard-wired. We can control our attention, but once we think an object is the most interesting thing to watch, we cannot suppress the pursuit. If the pursuit system is damaged, the eyes will fall behind a moving target. If it is still interesting, we will then catch up to the target using the saccade system. In that case, the eyes “track” a moving target not by the smooth pursuit movement, but by rapid short jumps to where the target has shifted. This will also happen in normal individuals if the pursuit system is partially shut down because of incomplete attention.
VOR: The third system, called the VOR (for Vestibulo-Ocular Reflex) is active all the time that we are awake, even in the dark. It receives signals from the balance organ in the ears to adjust the eyes for any head movement. With head rotation, the ears send a signal to the central switching center for lateral eye movements to keep the eyes positioned upon the original target.
Most of the time we watch one thing, and the pursuit system is actively maintaining eye position on the object of our attention. Once attention has shifted, the pursuit system is switched to the saccade system, and the eyes fly to the new target of our attention. The pursuit system then turns on again to maintain eye position directed to the new object for as long as it remains interesting. All the while that these two systems switch back and forth, the VOR is in the background, adjusting the eye position to respond to movement of the head in relation to the visual target.
Generally, when attention shifts from one place to another, normal people will turn their head to the new place of attention. For example, with a shift of attention from right to left, the head will also shift position from right to left. A complex set of adjustments that involves both the saccade and the VOR makes it possible for the eyes to shift correctly given the movement of the head. In this example, the brain will program a saccade to shift the eyes from right to left, measured correctly for the distance to the new target. At the same time, however, with the shift of the head from right to left, the VOR subtracts from that shift the right amount so that the eyes do not overshoot the new target. If the head shifts completely, the result is that there is no movement of the eye – the eye stays in the center of the orbit and the head shifts to the new target. There is a perfect balance between the saccade forces of right to left and the VOR forces of left to right.
Individuals with A-T usually develop problems with saccades and pursuits. The VOR system, and the actual final motor centers that add and subtract the signals from the saccade, pursuit and VOR, remain normal. The combination of the specific kind of saccade problem, impaired pursuit, and the normal VOR causes the “peculiarity of eye movements” (sometimes called oculomotor apraxia) that is seen often in A-T.
In A-T, saccades are abnormal in latency, so that it takes more time for the saccade to start after attention has shifted to a new object. Saccades also tend to be hypometric, or smaller than necessary to reach the target. Often a second, third or fourth saccade is necessary to shift the eyes all the way to the target. When the saccade driving the eye is impaired, the abnormal balance of the saccade versus the VOR becomes apparent. In the above example, with a shift of attention from right to left, the increased time to begin a saccade causes the eyes to be left behind as the normal VOR drives the eyes to the right to compensate for the shift of the head to the left. Only after a second will the eyes begin their saccade to the new object, which is now in front of the face because of the quick head shift. The eyes may require several hypometric saccades to finally be able to center on the new target of visual attention.
Individuals with A-T also have problems with pursuit movements. When an object moves to one side, they often have to use the saccade system (with all of the troubles that entails) to keep the eyes on or near to the target. There is also a problem in the balance between the impaired pursuit system and the normal VOR. This is more difficult to see when looking at a child with A-T in everyday life, but is one of the earliest abnormal features in the eye movements observed by a trained neurologist. As the head tracks a slowly moving object, say a dog walking from right to left, the eyes will be left behind even though the head is accurately moving with the target.
The face, voice and swallowing
Similar to the other neurologic impairments of A-T, problems with the face and bulbar muscles (the term for the muscles of the mouth and throat) are variable between individuals but quite distinctive in character.
Neurologists distinguish between speech and language, because brain problems may affect either one quite differently. Brain problems that disturb language in specific ways are called aphasia. A person with aphasia will have difficulty comprehending, processing or speaking normal language but will have normal ability to produce all of the sounds that make speech. In contrast, difficulty with the actual production of speech is called dysarthria. Although this can sometimes be quite difficult to determine, the available evidence strongly suggests that much of the difficulty with communication in A-T is a form of dysarthria. Children with A-T generally can articulate many of the basic speech sounds. They have trouble, however, combining sounds quickly to form words and sentences. Over time, or in many cases from the time of earliest words, children with A-T speak in a distinctive way. Sentences are short, the voice is soft, and there is a delay in the initiation of speech. When patient listeners give a person with A-T the opportunity to speak, the speech is often easier to understand than might be expected. In this respect, A-T appears to be different from many of the other ataxic disorders.
In day-to-day conversation, we use both verbal (speech) and nonverbal communication. Nonverbal communication refers to facial gestures and bodily movements that enhance the meaning of what we say or even communicate without words what we mean. We learn a great deal by attending to the eye movements and subtle facial movements of the persons to whom we are speaking. This is the reason why we speak differently with others over the phone than we would when speaking “face to face.” Many individuals with A-T have a diminished amount of these spontaneous expressive movements of the face. Large facial movements, such as a broad smile or frown, are relatively preserved. The lower face seems often seems to be more affected, so that the eyebrows may retain more expressiveness than the rest of the face. This difficulty with facial expression may falsely give the impression that a child with A-T is uninterested in, or unaware of, the topic of conversation. It can also subconsciously frustrate listeners. Those who know children and adults with A-T well learn to compensate for loss of this other “channel” of communication. Children who appear uninterested in a conversation may later recap many of the essential details or provide a summary that aptly describes the whole of the interaction.
Difficulties with swallowing and aspiration of food and saliva (getting into the windpipe) are quite common, especially in A-T patients over the age of 10 years (see Chapter 7). Why aspiration is so common in A-T is unknown. Although there are some distinctive features of the swallowing difficulty in A-T, it is also true that problems with silent aspiration occur commonly in other neurologic disorders. The primary protective reflexes (e.g. gagging) of the oropharnyx appear to be normal, but more complicated higher centers and reflexes of swallowing may be the focus of the neurologic abnormality.
The peripheral nerves
Many of the other disorders that are characterized by ataxia have a prominent peripheral neuropathy, or damage to the sensory or motor nerves that carry impulses between the limbs and the spinal cord. A-T shares this feature. In A-T, both the sensory and the motor nerves are affected. The neuropathy of A-T, however, is generally mild during the child’s early years, and the first clinical signs of the neuropathy are generally not apparent until early in the second decade. Few children are impaired by the neuropathy over and above the troubles that they have with central control of movement. Curiously, some of the individuals with a mild form of A-T may have relatively more problems with the neuropathy than with coordination. In those individuals, weakness and diminished sensation in the feet can add to the difficulties with central coordination when the latter develops more slowly.
Some Notes about Neurologic Therapies
Other sections of this manual include much of what is known to be of help in A-T. In general, it has not been useful to try to improve a problem by specific training in the impairment. For example, writing legibility is rarely improved with increasing practice. However, there is definitely a role for therapy in suggesting, evaluating and refining various work-arounds that might be of use in accomplishing the same or similar tasks using a different strategy. These work-arounds are useful at all stages of the disease, sometimes come naturally, and sometimes come from useful or innovative insights from therapists.
At present, no medication has been shown to be useful for the problems of movement in all patients. Drugs that are useful in the treatment of other movement disorders, such as Parkinson’s disease, could be of use for individual patients with specific movement problems. This is an area that needs careful and systematic investigation.
Some special note about the problems with reading may be of value here. The problems with reading are related to the increasing difficulty in moving the eyes quickly from one point of attention to the next. Thus reading almost always remains possible, but it eventually becomes more effort than it is worth. It is like trying to read a book while riding on a bumpy train – while it is possible to read, it is difficult to retain what is read and enjoy the process. Although reading is an important part of learning, it may be worthwhile to invest early in developing work-arounds for a time when reading becomes more difficult. As an example, people naturally learn by different methods. Some take careful notes; others listen intently to lectures; and others sleep through class and read the text and notes of classmates in the middle of the night. These differences probably reflect the various skills that individual students learn to exploit to their best advantage. Learning from auditory input – careful listening – is not everyone’s preferred means of learning, but for individuals with A-T it is definitely one dimension of neurologic function that remains possible for many years while other abilities are lost. Thus it may be worthwhile to cultivate critical listening even while reading is possible, in order to develop a skill that will be present always while other areas become more difficult.
Disclaimer: The information provided on this website should NOT be used as a substitute for seeking professional medical diagnosis, treatment or care. You should not rely on any information in these pages to replace consultations with qualified health professionals.