Faculty Bibliography

Acquired and congenital nystagmus often causes decreased visual acuity as a direct result of the inability to maintain stable foveal vision. In addition, acquired nystagmus causes a disabling subjective sensation of movement of the visual world called oscillopsia. The eye movements themselves do not require treatment if the patient is asymptomatic. However, therapy is necessary if visual disability is present. Treatments based in pharmacologic mechanisms are preferred. There are few controlled treatment trials and therapeutic efficacy generally is sought in a trial and error approach, depending on the type of nystagmus present. Treatment with 3,4-diaminopyridine and 4-aminopyridine recently have been shown to be effective for downbeat nystagmus. Gabapentin, baclofen, and clonazepam also are useful in some patients with downbeat nystagmus. Baclofen is the therapy of choice for periodic alternating nystagmus. Gabapentin often is effective for acquired pendular nystagmus. Clonazepam and valproate also may be effective for acquired pendular nystagmus. Memantine now is available in the United States and is promising in the treatment of pendular nystagmus. Optical devices that negate the negative effects of nystagmus continue to undergo development research. These and other medical, surgical, and optical devices are potentially useful alone or in combination with other therapies.

PURPOSE OF REVIEW: To review recent clinical data on ischemic optic neuropathies, which are some of the most frequently encountered optic neuropathies. These disorders include nonarteritic anterior ischemic optic neuropathy, arteritic anterior ischemic optic neuropathy, and posterior ischemic optic neuropathy. RECENT FINDINGS: Recent studies have facilitated our understanding of the natural history of visual loss, recovery, and recurrence in these disorders. Additionally, the value of various diagnostic techniques and treatment options, particularly for arteritic anterior ischemic neuropathy, has been clarified. SUMMARY: Application of the studies described in this paper should allow the clinician to more accurately diagnose ischemic optic neuropathies and counsel the patient with regard to appropriate management, prognosis for visual recovery and future risk of recurrence.

BACKGROUND: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells. OBJECTIVE: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies. METHODS: Fourteen patients with biochemically confirmed LOTS (8 men; age range 24 to 53 years; disease duration 5 to 30 years) and 10 age-matched control subjects were studied. Snellen visual acuity, contrast sensitivity, color vision, stereopsis, and visual fields were measured, and optic fundi were photographed. Horizontal and vertical eye movements (search coil) were recorded, and saccades, pursuit, vestibulo-ocular reflex (VOR), vergence, and optokinetic (OK) responses were measured. RESULTS: All patients showed normal visual functions and optic fundi. The main eye movement abnormality concerned saccades, which were "multistep," consisting of a series of small saccades and larger movements that showed transient decelerations. Larger saccades ended earlier and more abruptly (greater peak deceleration) in LOTS patients than in control subjects; these changes can be attributed to premature termination of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were reduced, but VOR, vergence, and gaze holding were normal. CONCLUSIONS: Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of saccades but normal afferent visual systems. Hypometria, transient decelerations, and premature termination of saccades suggest disruption of a "latch circuit" that normally inhibits pontine omnipause neurons, permitting burst neurons to discharge until the eye movement is completed. These measurable abnormalities of saccades provide a means to evaluate the effects of novel treatments for LOTS.

A 68-year-old woman with a relatively acute onset of right homonymous hemianopia, Gerstmann syndrome, and global cognitive failure was found to have a lymphocytic pleocytosis and elevated protein on spinal fluid examination and displayed marked meningeal enhancement on magnetic resonance imaging and dilated cortical venules on cerebral angiography. Brain and meningeal biopsy disclosed a necrotizing granulomatous inflammation of small and medium-sized subarachnoid vessels. The brain parenchyma was normal. The angiographic presence of venous abnormalities, the lack of observable angiographic arterial involvement, and the lack of parenchymal pathology are distinctly unusual in granulomatous angiitis of the central nervous system. This case, therefore, extends the pathologic and imaging spectrum of this disorder.

PURPOSE: To elucidate the relationship between anemia and raised intracranial pressure (ICP). DESIGN: Interventional case series. METHODS: Retrospective case series and review of the literature. Only patients with documented papilledema, neuroimaging ruling out a space-occupying lesion, and anemia were included. RESULTS: Five women with confirmed idiopathic intracranial hypertension (IIH) (normal brain magnetic resonance imaging, normal cerebrospinal fluid, elevated intracranial pressure), and one man with presumed IIH (normal head computed tomography [CT], no lumbar puncture) were evaluated. All had bilateral papilledema associated with peripapillary hemorrhages. Two had retinal cotton-wool spots (CWS), and two had preretinal hemorrhages. All had severe iron deficiency anemia, which was discovered at the time of their ocular complaints in five of them. Their symptoms and signs improved dramatically after treatment of the anemia. We found 30 well-documented cases in the English and French literature. Among those, 13 were excluded from our analyses (11 had confounding disorders, and two had cerebral venous thrombosis). In the remaining 17 cases, isolated raised ICP associated with anemia was the most likely diagnosis, although in none of these cases was cerebral venous thrombosis excluded. CONCLUSIONS: Anemia may play a role in the occurrence of raised ICP and papilledema. Although only a few cases in the literature support this association, it may be more common than previously thought. Because most patients are not known to be anemic when papilledema is discovered, we suggest that a complete blood count be obtained in patients with IIH, especially in the absence of known associated factors such as obesity or medications or when treatment aimed at lowering ICP fails to improve the patient's symptoms. The underlying mechanisms remain unknown, but cerebral venous thrombosis should be carefully excluded.

A 23-year-old woman who presented with a branch retinal artery occlusion followed by encephalopathy showed, by brain magnetic resonance imaging, a nonenhancing lesion in the right parietal gray matter with normal diffusion-weighted imaging. Of 64 reported cases of cat-scratch encephalopathy with documented neuroimaging findings, only 12 (18.8%) have had abnormal imaging findings. The abnormalities have included cerebral white matter lesions, basal ganglia and thalamic lesions, and multifocal lesions in immunocompromised patients, but no gray matter lesions similar to those in this patient. The variety of neuroimaging findings supports multiple pathophysiologic mechanisms of central nervous system involvement in this disorder.