Neuro-ophthalmology of late-onset Tay–Sachs disease (LOTS)

Abstract

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.

Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment

“…Muscle weakness may therefore not have been a suitable measure for detecting therapeutic benefits in this patient cohort. Recent studies have suggested that ophthalmologic measures 33 or neuropsychological measures 34 might be useful in the assessment of therapeutic interventions of patients with G M2 gangliosidosis. In particular, memory and executive functioning (e.g., problem solving and planning) impairments have been shown to occur frequently in LOTS patients, thus neuropsychological tests might be an alternative method of measuring the effect of treatment on cortical involvement.…”

"Cherry red spot" in a patient with Tay-Sachs disease: case report

“…Is a sphingolipidosis characterised by deficiency of lysosomal enzymes required to sphingolipids degradation: gangliosides, cerebrosides and sphingomyelins (2) . Tay-Sachs is characterized by lesions in the central nervous system due to the accumulation of GM2 trihexosylceramide in neurocytes (3) , a disorder of sphingolipid metabolism caused by enzyme β hexosaminidase A deficiency (4) . Infantile Tay-Sachs disease is characterized by normal development until 4 to 5 months of age, followed by progressive psychomotor retardation, megalencephaly, retinal "cherry red spot", blindness, and death by the age of 3 to 5 years (4) .…”

Mechanism of interrupted saccades in patients with late-onset Tay–Sachs disease

“…We used eye movements recorded with coils in 14 patients diagnosed with LOTS and 10 healthy control subjects (for details, see Rucker et al, 2004). Horizontal saccades were simulated in Matlab (Mathworks, Natick, MA).…”

“…Patients with LOTS typically make a series of small saccades in response to a target jump, but their peak speeds seem normal (Rucker et al, 2004). LOTS saccades are interrupted by transient decelerations, not always coming to a standstill, after which a new saccade occurs.…”