Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, auto somal recessive, progressive variant of GM2 gangliosidosis, characterized by inv olvement of the cerebellum and anterior horn cells. Abstract Obj...Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, auto somal recessive, progressive variant of GM2 gangliosidosis, characterized by inv olvement of the cerebellum and anterior horn cells. Abstract Objective: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluati ng the effectiveness of novel therapies. Methods: Fourteen patients with biochem ically 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 acuit y, contrast sensitivity, color vision, stereopsis, and visual fields were measur ed, and optic fundi were photographed. Horizontal and vertical eye movements (se arch 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 abnormalit y concerned saccades, which were “ multistep,” consisting of a series of smal l saccades and larger movements that showed transient decelerations. Larger sacc ades ended earlier and more abruptly (greater peak deceleration) in LOTS patient s than in control subjects; these changes can be attributed to premature termina tion of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were redu ced, but VOR, vergence, and gaze holding were normal. Conclusions: Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of sa ccades 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.展开更多
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: ...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.展开更多
文摘Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, auto somal recessive, progressive variant of GM2 gangliosidosis, characterized by inv olvement of the cerebellum and anterior horn cells. Abstract Objective: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluati ng the effectiveness of novel therapies. Methods: Fourteen patients with biochem ically 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 acuit y, contrast sensitivity, color vision, stereopsis, and visual fields were measur ed, and optic fundi were photographed. Horizontal and vertical eye movements (se arch 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 abnormalit y concerned saccades, which were “ multistep,” consisting of a series of smal l saccades and larger movements that showed transient decelerations. Larger sacc ades ended earlier and more abruptly (greater peak deceleration) in LOTS patient s than in control subjects; these changes can be attributed to premature termina tion of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were redu ced, but VOR, vergence, and gaze holding were normal. Conclusions: Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of sa ccades 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.
文摘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.
