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386 Clinical Pathways in Neuro-Ophthalmology, second edition
disease, midline medullary lesions, posterior midline cerebellar lesions, or diffuse
cerebellar disease (Buttner, 1995; Walker, 1999). Most responsible lesions affect the
vestibulocerebellum (flocculus, paraflocculus, nodulus, and uvula) and the underlying
medulla. Deficient drive by the posterior semicircular canals, whose central projections
cross in the floor of the fourth ventricle, has been postulated as an explanation for
downbeat nystagmus. Interruption of downward vestibulo-ocular reflex pathways,
which synapse in the medial vestibular nucleus and cross in the medulla (beneath the
nucleus prepositus hypoglossi) to reach the contralateral medial longitudinal fasciculus,
would result in upward smooth eye drift and a downward corrective saccade.
Cerebellar, especially floccular and uvulonodular, lesions may cause this nystagmus
by disinhibition of the cerebellar effect on the vestibular nuclei. The cerebellar flocculus
contains Purkinje cells that send inhibitory projections to the anterior canal but not
posterior canal central pathways; therefore, disinhibition would lead to downbeat
nystagmus. Damage to the nuclei propositus hypoglossi and the medial vestibular
nuclei (the neural integrator) in the medulla has also been suggested as the cause of
the nystagmus. A patient with acute multiple sclerosis with a lesion of the caudal
medulla (which contains Roller’s nucleus and nucleus intercalatus) developed downbeat
nystagmus upon horizontal head oscillations (perverted head-shaking nystagmus)
(Minagar, 2001). Etiologies of downbeat nystagmus are listed in Table 17–3.
The evaluation of downbeat nystagmus depends on the clinical circumstances and
associated neurologic findings. We recommend MRI in patients with unexplained
downbeat nystagmus (Himi, 1995) (class IV, level C). MRI is normal or shows diffuse
cerebellar atrophy in patients with familial cerebellar degenerations. In patients taking
anticonvulsants or lithium, drug levels should be measured and adjusted as needed
(class IV, level C). If MRI is normal, B12 and magnesium levels should be considered
(class IV, level C). Thiamine therapy for selected cases should be considered and the
possibility of alcohol or toluene abuse investigated (class IV, level C). If there are signs
suggestive of CNS infection, a spinal tap may be warranted. In a patient with downbeat
nystagmus with the acute or subacute onset of cerebellar signs and symptoms, a
paraneoplastic process must be considered, especially due to small cell lung cancer,
testicular cancer, gynecologic cancers (especially ovarian and breast cancer), and
Hodgkin’s disease. The workup of these patients might include serum anti-Yo (anti-
Purkinje cell) antibodies, serum anti-Hu antibodies (antineuronal nuclear antibodies
type 1 or ANNA type 1), serum anti-Ta antibodies, chest x-ray and chest computed
tomography (CT) imaging, gynecologic examination, CT or MRI of the abdomen and
pelvis, mammography, and possibly hematologic consultation for bone marrow biopsy
(class IV, level C).
Finally, in a significant number of individuals, no etiology for the downbeat
nystagmus will be discovered. Young and Huang reported the use of clonazepam
(1.0 mg twice daily) in five idiopathic cases of downbeat nystagmus (Young, 2001).
Damage to the central projections of the anterior semicircular canals, which tend to
deviate the eyes superiorly, has been suggested to explain upbeat nystagmus. Upbeat
nystagmus is usually worse in upgaze (Alexander’s law) and, unlike downbeat
nystagmus, it usually does not increase on lateral gaze. Convergence may increase or
decrease the nystagmus, or convert downbeat nystagmus to upbeat nystagmus (Hirose,
1991). Damage to the ventral tegmental pathways, which may link the superior
vestibular nuclei to the superior rectus and inferior oblique subnuclei of the oculomotor
nuclei, may cause the eyes to glide down, resulting in upbeat nystagmus. Medullary