Ataxia may be present in the limbs if there is pathology of the cerebellar hemispheres. This can be demonstrated on finger–nose and heel–shin testing, and by testing the patient’s ability to rapidly mirror the examiner’s movements (see “Examination of coordination” in Ch. 1). Gait instability/ataxia may be present if there is midline cerebellar (vermis) pathology.
When a patient presents with clumsiness, incoordination, and/or difficulty walking, the history and evaluation must determine whether such symptoms are due to sensory disturbances, weakness, or ataxia. If the problem is indeed ataxia, it is important to note that the lesion is not necessarily cerebellar. The cerebellum is only as good as its inputs and outputs. For example, a lesion affecting any of the cerebellar peduncles can lead to cerebellar ataxia by depriving the cerebellum of the inputs and outputs necessary to perform its functions. Ataxia can also be seen with disruption of the corticopontocerebellar fibers in their descent in the internal capsule or anterior pons, as demonstrated by the ataxia-hemiparesis and dysarthria-clumsy hand lacunar syndromes (see Ch. 7). If the cerebellum does not receive adequate proprioceptive information (from the inferior cerebellar peduncles), it cannot adequately coordinate movements. Therefore, problems anywhere along the dorsal column pathways (large fiber neuropathy, sensory ganglionopathy, pathology of the dorsal columns in the spinal cord) can lead to a type of ataxia known as sensory ataxia.
Distinguishing Cerebellar Ataxia From Sensory Ataxia
Ataxia due to cerebellar causes may be accompanied by additional cerebellar signs such as nystagmus (see Ch. 12), titubation (oscillation of the head and/or trunk at rest), and/or dysarthria (Table 8–1). Such findings should not be present if ataxia is caused by sensory dysfunction due to neuropathy, ganglionopathy, or dorsal column dysfunction (unless there is also concurrent cerebellar pathology). If there is a sensory etiology of ataxia, other sensory signs may be present such as diminished proprioception and vibration sense and Romberg’s sign. If sensory dysfunction is due to peripheral nervous system pathology (i.e., nerves, dorsal root ganglia, or dorsal roots), diminished or absent reflexes may be present.
TABLE 8–1Distinguishing Cerebellar Ataxia From Sensory Ataxia. ||Download (.pdf) TABLE 8–1 Distinguishing Cerebellar Ataxia From Sensory Ataxia.
| ||Cerebellar Ataxia ||Sensory Ataxia |
|Finger–nose testing ||Intention tremor || |
Worsens with eyes closed
|Accompanying features || |
(Hyporeflexia or areflexia if due to neuropathy or ganglionopathy)
|Gait ||Wide based ||Wide based |
Romberg’s sign is commonly mistakenly attributed to cerebellar pathology, but it is actually a sign of impaired proprioception. Patients with severe cerebellar dysfunction are often unable to stand with their feet together even with their eyes open, let alone closed. Patients with a deficit in proprioception can stand with their feet together when using vision to compensate, but closing the eyes removes this cue and requires the patient to rely exclusively on proprioception, so the patient may lose her/his balance (Romberg sign).
On finger–nose testing, cerebellar and sensory ataxia have different appearances. Cerebellar ataxia appears as an oscillatory movement perpendicular to the plane of movement (i.e., side-to-side when the patient approaches the target in the finger-nose task) and worsens as the patient approaches the target. Sensory ataxia causes what resembles a “searching” movement in which the affected limb looks as if it is approaching the target with meandering, circular movements. With slow movements under visual guidance, a patient with sensory ataxia may be able to gain reasonable accuracy with finger–nose testing. However, if the examiner leaves the target finger in the same place and asks the patient to continue going back and forth from nose to finger with the eyes closed, the patient will become increasingly inaccurate. This is because removing the patient’s visual compensation requires complete reliance on proprioception, which is impaired in sensory ataxia.
An additional subtle sign of diminished proprioception that may be seen is pseudoathetosis. Athetosis is a movement disorder characterized by writhing movements (see Ch. 23). In a patient with diminished proprioception, when the patient’s arms and hands are stretched out in front of her/him with the eyes closed (as in testing pronator drift), subtle writhing piano playing–like movements of the fingers may be noted. Similar movements of the toes may be noted when testing for Romberg’s sign. These movements may be the digits trying to “find themselves in space” without adequate proprioception to serve that function, and are referred to as pseudoathetosis.
Differential Diagnosis of Cerebellar Ataxia
As with any neurologic problem, once localized, the differential diagnosis arises from an understanding of the time course of symptom onset and evolution.
Hyperacute-onset (over seconds to hours) of cerebellar pathology can be caused by:
Acute- to subacute-onset (over hours to days) of cerebellar pathology can be caused by:
Postinfectious cerebellitis (most commonly seen in children after a viral illness, most commonly varicella infection)
Flare of multiple sclerosis (see Ch. 21)
Subacute to chronic-onset (over weeks to months) of cerebellar pathology can be caused by:
Infection: progressive multifocal leukoencephalopathy (see Ch. 20)
Paraneoplastic cerebellar degeneration, which can be associated with anti-Yo (ovarian and breast cancer), anti-Hu (small cell lung cancer), anti-Tr (Hodgkin’s lymphoma), anti-Ma2 (testicular cancer), and anti-GAD (often not associated with a malignancy) antibodies (see Ch. 24)
Tumor: medulloblastoma (in children), metastatic tumor (in adults)
Metabolic causes: vitamin E deficiency
Chronic-onset (over months to years) of cerebellar pathology can be caused by:
Vascular, infectious, multiple sclerosis lesion–related, and malignant etiologies of cerebellar disease usually lead to unilateral cerebellar dysfunction, whereas drug-related, metabolic, degenerative, and non-multiple sclerosis inflammatory etiologies (e.g., paraneoplastic or postinfectious) more commonly lead to bilateral cerebellar dysfunction.
Most of these etiologies of cerebellar dysfunction are discussed in Part 2 of this book except the inherited ataxias, which are therefore discussed here.
Inherited Causes of Cerebellar Ataxia
Friedreich’s ataxia—This autosomal recessively inherited ataxia affects the spinocerebellar tracts as well as the dorsal columns, corticospinal tracts, and peripheral nerves. In addition to ataxia and sensory loss developing in young adulthood, most patients develop cardiomyopathy. The causative mutation is in the frataxin gene (caused by GAA repeat).
Spinocerebellar ataxia—This term is applied to a growing number (more than 30) of autosomal dominantly inherited ataxias that are all characterized by adult-onset ataxia, but which can have a variety of additional features such as pyramidal, extrapyramidal, or cognitive dysfunction, and/or neuropathy. The most common spinocerebellar ataxia (SCA) is SCA3 (Machado-Joseph disease), which causes cerebellar dysfunction, cognitive impairment, neuropathy, and, in some cases, extrapyramidal features (e.g., parkinsonism; see Ch. 23). The highest prevalence of SCA3 is in the Azores, and the causative mutation is in the ATXN3 gene (caused by CAG repeat).
Fragile X–associated tremor/ataxia syndrome (FXTAS)—An adult-onset progressive ataxia called fragile X–associated tremor/ataxia syndrome (FXTAS) can be caused by mutations in the same gene (FMR1) that causes fragile X syndrome (a common cause of mental retardation in boys, accompanied by dysmorphic facial features and large testicles). FXTAS occurs in patients with a fewer number of trinucelotide (CGG) repeats than are necessary to produce fragile X syndrome (e.g., in the parent or grandparent of a child with fragile X syndrome), referred to as a premutation. As an X-linked condition, the disorder most commonly occurs in men, but can rarely occur in women in a milder form. Onset of cerebellar ataxia begins most commonly after age 50, and may be accompanied by parkinsonism and/or dementia. A characteristic MRI finding is T2/FLAIR hyperintensities in the bilateral middle cerebellar peduncles (Fig. 8–5).
Axial FLAIR MRI in fragile X-associated tremor ataxia syndrome (FXTAS) demonstrating bilateral hyperintensities in the middle cerebellar peduncles.