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Harrison’s Manual of Medicine



Clinical Presentation
Inherited Ataxias

Clinical Presentation
Symptoms and signs of ataxia may include gait instability, nystagmus, dysarthria (scanning speech), impaired limb coordination, intention tremor (i.e., with movement), hypotonia. Differential diagnosis: Unsteady gait associated with vertigo can resemble gait instability of cerebellar disease but produces a sensation of head movement, dizziness, or light-headedness. Bilateral proximal leg weakness or sensory ataxia, in particular with neuropathies (e.g., Fisher variant of Guillain-Barré syndrome), can also simulate cerebellar ataxia.

Approach to the Patient

Causes are best grouped by determining whether ataxia is symmetric or asymmetric and by the time course (Table 190-1). It is also important to distinguish whether ataxia is present in isolation or is part of a multisystem neurologic disorder. Acute symmetric ataxia is usually due to medications, toxins, viral infection, or a postinfectious syndrome (especially varicella). Subacute or chronic symmetric ataxia can result from hypothyroidism, vitamin deficiencies, infections, alcohol, and other toxins. Progressive nonfamilial cerebellar ataxia after age 45 suggests a paraneoplastic syndrome, either subacute cortical cerebellar degeneration (ovarian, breast, small cell lung, Hodgkin’s) or opsoclonus- myoclonus (neuroblastoma, breast).

Table 190-1 Etiology of Cerebellar Ataxia

Unilateral ataxia suggests a focal lesion in the ipsilateral cerebellar hemisphere or its connections. An important cause of acute unilateral ataxia is stroke. Mass effect from cerebellar hemorrhage or swelling from ischemic cerebellar infarction can compress brainstem structures, producing altered consciousness and ipsilateral pontine signs (small pupil, lateral gaze or sixth nerve paresis, facial weakness); limb ataxia may not be prominent. Other diseases resulting in subacute-to-chronic unilateral or asymmetric ataxia include tumors, multiple sclerosis, progressive multifocal leukoencephalopathy (immunodeficiency states) or congenital malformations.

Inherited Ataxias
May be autosomal dominant, autosomal recessive, or mitochondrial (maternal inheritance); 24 different disorders recognized (Table 364-2, HPIM-15). Friedreich’s ataxia is most common; autosomal recessive; ataxia with areflexia, upgoing toes, vibration and position sensation deficits, cardiomyopathy, hammer toes, scoliosis; linked to expanded trinucleotide repeat in the intron of “frataxin” gene; a second genetic form of Friedreich’s is associated with vitamin E deficiency. Common dominantly inherited ataxias are spinocerebellar ataxia (SCA) 1 (olivopontocerebellar degeneration; “ataxin-1” gene) and SCA 3 (Machado-Joseph disease); both present with ataxia and brainstem and extrapyramidal signs; SCA 3 may also have dystonia and amyotrophy; genes for each disorder contain unstable trinucleotide repeats in coding region.
The differential diagnosis is driven by the symmetry and time course of the ataxia (Table 190-1). For symmetric ataxias, drug and toxicology screens; vitamin B1, B12, and E levels; thyroid function tests; antibody tests for syphilis and Lyme infection; paraneoplastic autoantibodies (anti-Yo, anti-Ri, anti-Hu); and CSF studies often indicated. Genetic testing is available for many inherited ataxias but should be carried out only with genetic counseling. For unilateral or asymmetric ataxias, brain MRI or CT scan is the initial test of choice.
Hypothyroidism, vitamin deficiency, infectious and parainfectious causes of ataxia are treatable. With paraneoplastic ataxias, identification of underlying cancer is important for the pt, but as a rule ataxia does not improve following treatment of tumor. Cerebellar hemorrhage and other mass lesions of the posterior fossa may require surgical treatment to prevent fatal brainstem compression.

For a more detailed discussion, see Rosenberg RN: Ataxic Disorders, Chap. 364, p. 2406, in HPIM-15.


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