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Eye movements in amyotrophic lateral sclerosis
64
Surv Ophthalmol 28( 1) July-August 1983
CURRENTOPHTHALMOLOGY
difficult to study cytogenetically, as there is chromosomal and surface antigen drift. The consistent chromosoma1 abnormality in both tumor stem lines was an absence of chromosome 13. No ESD activity was found in tumor tissue. This suggests that the deleted chromosome 13 was retained by the tumor; the normal chromosome 13 was lost. These authors postulate that the molecular action of the retinoblastoma gene is recessive; both retinoblastoma cancer gene alleles must be lost for tumors to develop. There have been two types of human “cancer genes” proposed. A deletional cancer gene is proposed for retinoblastoma characterized by a loss of genetic information. In some human tumors, cancer genes may alternatively function by gene activation. DEVRON CHAR SAN FRANCISCO
Eye Movements in Amyotrophic Lateral Sclerosis, by A. Leveille, J. Kiernan, J.A. Goodwin,
and J. Antel. Arch Neural 39:684-686,
1982
Amyotrophic lateral sclerosis (ALS) is a chronic progressive disease of unknown etiology affecting the upper motor neurons of the frontal cortex and the motor neurons of the brain stem and spinal cord. The rate of disease progression varies considerably. Although bulbar cranial nerve involvement is common, ocular motor nuclei involvement is rare, even in patients with advanced brain stem disease. Several previous reports have described neuronal loss and gliosis in the third, fourth and sixth cranial nerve nuclei, but the frequency of these changes is unknown. When these abnormalities occur, they usually do so only late in the patient’s course. The authors undertook to determine whether there was a frequent subclinical involvement of the ocular motor system and how a disease with proponently frontal lobe upper motor neuron loss and normal ocular motor neuron affects eye movements. Direct eye movement recordings were performed on ten patients with a diagnosis of amyotrophic lateral sclerosis. Of the ten patients with ALS studied, the four with rapidly progressive and advanced disease had decreased pursuit gains. Decreased smooth pursuit gain is most commonly reported with lesions in the parietal, occipital or brain stem areas. In two patients, normometric but slow saccadic eye movement without gaze paretic nystagmus was documented. A similar pattern in a patient with a pontine paramedian reticular formation lesion has been reported and a lesion in the direct pathway through the pontine integrator was postulated. Both the saccadic system and the smooth pursuit system defects were therefore seen in patients with ALS. We do not know how the frontal cortex modifies eye movements and how attrition offrontal lobe upper motor neurons may contribute to the eye movement abnormalities in this study. Further quantitative studies on the brain stem reticular formation and ocular motor nuclei in patients with ALS would be of interest in view of these eye movement findings. (Abstract by C. Hoyt)
Comment Amyotrophic lateral sclerosis is the most familiar clinical form of the motor neuron diseases, a heterogenous group of chronic,, progressive degenerations which affect both upper and lower motor neuronal functioning. The clinical expression of ALS occurs in characteristic patterns, with major manifestation in either anterior horn cells, pyramidal tract, or brain stem motor nuclei. While variation on these three themes is accepted, clinical axiom has been that the eye muscles are nearly always spared. An occasional patient is reported with ophthalmoplegia and ptosis, but clinicians since Charcot and Duchenne have looked for normal eye movements to confirm a diagnosis of ALS. If the concept of ALS as a system disease of motor neurons is correct, one might predict some ocular motor dysfunction in such patients, for the extraocular motor neurons are the final common pathway for all eye movements. A saccade in the LLon”direction is presaged by a transient increase in the frequency of discharge of motor neurons to the agonist muscle, just as this “pulse” is followed by a “step” increase in tonic discharge which is proportional to the programmed eye position. A slow movement of either pursuit or vestibular origin requires additional modulation of the rate of discharge of the extraocular motor neuron pool. It ought be no surprise, therefore, that sophisticated examination of the ocular motility apparatus in cases of ALS shows abnormalities. The authors employed DC electro-oculography to test horizontal volitional saccades and smooth pursuits. Ten affected patients were studied; eight healthy adults served as controls. Of the ten ALS patients, four had
65
CURRENTOPHTHALMOLOGY
marked bulbar atrophy, “advanced disease,” and a “rapidly progressive course.” This subgroup demonstrated abnormal eye movement recordings, though whether these anomalies were recognized by the bedside is not clearly stated. Decreased pursuit gain was apparent in all four; two had decreased saccadic velocities, while two others had abnormal pursuit velocities. One showed serial saccades at progressively decreasing peak velocity as well. Interpreting such findings in chronically ill patients can be difficult because of the effects of fatigue and inattention. The authors argue that their testing method employed frequent rest and verbal encouragement to minimize such nonspecific variables. They further argue that one case with unilateral defective pursuit suggests that results are due to factors other than fatigue. The arguments are not altogether convincing. Still, one suspects their observations are correct and their conclusion valid - that the oculomotor system is more than occasionally affected in ALS, and that the effect is a direct manifestation of a degenerative neurological disease and not an epiphenomenon. This confirms Jacobs’ previous report (Neurology 31: 1282-1287, 1981). Whether such phenomenology can be explained as infranuclear or supranuclear in origin remains highly speculative, however, and awaits quantitative and physiologic study of brain stem reticular formation and ocular motor nuclei in ALS patients.
BARRETTKATZ Tuc:soru, ARIZONA
The Use of the Sonic Guide in Infancy, by S. Aitken Blindness, March 1982, pp 9 l-l 00
and T.G.R.
Bauer.
V~xion Impairment and
In 1971 Bauer (Bauer TGR: Blind babies see with their ears. New Scientist 73:255-257, 1977) attempted to assess the possible facilitory effect of an ultrasonic sonar sensing device on the development of a blind child. The device used was a modified version of the sonic guide, manufactured by Wormald Vigilant. The sonic guide emits a continuous cone of ultrasonic sound. The sound bounces back off objects, returns to the guide, and is then converted to audible sound by means of two transducers. The sound consists of a mixture of signals. Pitch codes distance; amplitude codes size; timbre of signal codes texture; cortical time of arrival from each ear codes direction. The initial subject report by Bauer and his co-workers discusses developed perceptual motor abilities that are not normally seen in the blind child. It has not been reported as yet whether these early advantages will have any long-term beneficial effects. The study under review here is a longterm study in which specific questions are to be asked about the behavioral and motor development of blind infants aided with the sonic guide. The early results of this study are very encouraging and document that a number of children can show very sophisticated behavioral and motor development as a consequence ofperiodic use of a sonic guide device. This is most striking in children under 13 months of age and less striking following that period of time. In all children tested, ambulation as well as other signs of early motor development were greatly enhanced when compared with the control group who did not use the sonic guide. It is, of course, more important to answer the question of whether long-term developmental processes will also be enhanced by the use of this guide. It will be important to establish whether the guide is being used as a perceptual surrogate in a manner formally analogous to vision, in which case one would expect the infants to develop along the lines of a sighted infant, not those of a congenitally blind one. This will, of course, require that the guide be used like vision to promote and/or establish new behaviors. In addition to response transfer, then, it is argued that with long-term users a second criteria for spontaneous or perceptual usage should be the observation of the emergence of new behaviors, behaviors that would otherwise not be observed in the development of the normal congenitally blind infant. Currently, a study is in progress in which specific questions will be asked along these lines. (Abstract by C. Hoyt)
Comment In this fascinating and thought-provoking study, the authors suggest the periodic use of a sonar device by blind infants will not only enhance their short-term motor development but may, in fact, alter permanently their long-term behavioral and motor development. This is based upon their own preliminary short-term study of ten infants tested from five months to 25 months with various causes of congenital blindness. It is important to note that one of the major methodoIogy problems in this paper and in all papers addressing the
Surv Ophthalmol 28( 1) July-August 1983
CURRENTOPHTHALMOLOGY
difficult to study cytogenetically, as there is chromosomal and surface antigen drift. The consistent chromosoma1 abnormality in both tumor stem lines was an absence of chromosome 13. No ESD activity was found in tumor tissue. This suggests that the deleted chromosome 13 was retained by the tumor; the normal chromosome 13 was lost. These authors postulate that the molecular action of the retinoblastoma gene is recessive; both retinoblastoma cancer gene alleles must be lost for tumors to develop. There have been two types of human “cancer genes” proposed. A deletional cancer gene is proposed for retinoblastoma characterized by a loss of genetic information. In some human tumors, cancer genes may alternatively function by gene activation. DEVRON CHAR SAN FRANCISCO
Eye Movements in Amyotrophic Lateral Sclerosis, by A. Leveille, J. Kiernan, J.A. Goodwin,
and J. Antel. Arch Neural 39:684-686,
1982
Amyotrophic lateral sclerosis (ALS) is a chronic progressive disease of unknown etiology affecting the upper motor neurons of the frontal cortex and the motor neurons of the brain stem and spinal cord. The rate of disease progression varies considerably. Although bulbar cranial nerve involvement is common, ocular motor nuclei involvement is rare, even in patients with advanced brain stem disease. Several previous reports have described neuronal loss and gliosis in the third, fourth and sixth cranial nerve nuclei, but the frequency of these changes is unknown. When these abnormalities occur, they usually do so only late in the patient’s course. The authors undertook to determine whether there was a frequent subclinical involvement of the ocular motor system and how a disease with proponently frontal lobe upper motor neuron loss and normal ocular motor neuron affects eye movements. Direct eye movement recordings were performed on ten patients with a diagnosis of amyotrophic lateral sclerosis. Of the ten patients with ALS studied, the four with rapidly progressive and advanced disease had decreased pursuit gains. Decreased smooth pursuit gain is most commonly reported with lesions in the parietal, occipital or brain stem areas. In two patients, normometric but slow saccadic eye movement without gaze paretic nystagmus was documented. A similar pattern in a patient with a pontine paramedian reticular formation lesion has been reported and a lesion in the direct pathway through the pontine integrator was postulated. Both the saccadic system and the smooth pursuit system defects were therefore seen in patients with ALS. We do not know how the frontal cortex modifies eye movements and how attrition offrontal lobe upper motor neurons may contribute to the eye movement abnormalities in this study. Further quantitative studies on the brain stem reticular formation and ocular motor nuclei in patients with ALS would be of interest in view of these eye movement findings. (Abstract by C. Hoyt)
Comment Amyotrophic lateral sclerosis is the most familiar clinical form of the motor neuron diseases, a heterogenous group of chronic,, progressive degenerations which affect both upper and lower motor neuronal functioning. The clinical expression of ALS occurs in characteristic patterns, with major manifestation in either anterior horn cells, pyramidal tract, or brain stem motor nuclei. While variation on these three themes is accepted, clinical axiom has been that the eye muscles are nearly always spared. An occasional patient is reported with ophthalmoplegia and ptosis, but clinicians since Charcot and Duchenne have looked for normal eye movements to confirm a diagnosis of ALS. If the concept of ALS as a system disease of motor neurons is correct, one might predict some ocular motor dysfunction in such patients, for the extraocular motor neurons are the final common pathway for all eye movements. A saccade in the LLon”direction is presaged by a transient increase in the frequency of discharge of motor neurons to the agonist muscle, just as this “pulse” is followed by a “step” increase in tonic discharge which is proportional to the programmed eye position. A slow movement of either pursuit or vestibular origin requires additional modulation of the rate of discharge of the extraocular motor neuron pool. It ought be no surprise, therefore, that sophisticated examination of the ocular motility apparatus in cases of ALS shows abnormalities. The authors employed DC electro-oculography to test horizontal volitional saccades and smooth pursuits. Ten affected patients were studied; eight healthy adults served as controls. Of the ten ALS patients, four had
65
CURRENTOPHTHALMOLOGY
marked bulbar atrophy, “advanced disease,” and a “rapidly progressive course.” This subgroup demonstrated abnormal eye movement recordings, though whether these anomalies were recognized by the bedside is not clearly stated. Decreased pursuit gain was apparent in all four; two had decreased saccadic velocities, while two others had abnormal pursuit velocities. One showed serial saccades at progressively decreasing peak velocity as well. Interpreting such findings in chronically ill patients can be difficult because of the effects of fatigue and inattention. The authors argue that their testing method employed frequent rest and verbal encouragement to minimize such nonspecific variables. They further argue that one case with unilateral defective pursuit suggests that results are due to factors other than fatigue. The arguments are not altogether convincing. Still, one suspects their observations are correct and their conclusion valid - that the oculomotor system is more than occasionally affected in ALS, and that the effect is a direct manifestation of a degenerative neurological disease and not an epiphenomenon. This confirms Jacobs’ previous report (Neurology 31: 1282-1287, 1981). Whether such phenomenology can be explained as infranuclear or supranuclear in origin remains highly speculative, however, and awaits quantitative and physiologic study of brain stem reticular formation and ocular motor nuclei in ALS patients.
BARRETTKATZ Tuc:soru, ARIZONA
The Use of the Sonic Guide in Infancy, by S. Aitken Blindness, March 1982, pp 9 l-l 00
and T.G.R.
Bauer.
V~xion Impairment and
In 1971 Bauer (Bauer TGR: Blind babies see with their ears. New Scientist 73:255-257, 1977) attempted to assess the possible facilitory effect of an ultrasonic sonar sensing device on the development of a blind child. The device used was a modified version of the sonic guide, manufactured by Wormald Vigilant. The sonic guide emits a continuous cone of ultrasonic sound. The sound bounces back off objects, returns to the guide, and is then converted to audible sound by means of two transducers. The sound consists of a mixture of signals. Pitch codes distance; amplitude codes size; timbre of signal codes texture; cortical time of arrival from each ear codes direction. The initial subject report by Bauer and his co-workers discusses developed perceptual motor abilities that are not normally seen in the blind child. It has not been reported as yet whether these early advantages will have any long-term beneficial effects. The study under review here is a longterm study in which specific questions are to be asked about the behavioral and motor development of blind infants aided with the sonic guide. The early results of this study are very encouraging and document that a number of children can show very sophisticated behavioral and motor development as a consequence ofperiodic use of a sonic guide device. This is most striking in children under 13 months of age and less striking following that period of time. In all children tested, ambulation as well as other signs of early motor development were greatly enhanced when compared with the control group who did not use the sonic guide. It is, of course, more important to answer the question of whether long-term developmental processes will also be enhanced by the use of this guide. It will be important to establish whether the guide is being used as a perceptual surrogate in a manner formally analogous to vision, in which case one would expect the infants to develop along the lines of a sighted infant, not those of a congenitally blind one. This will, of course, require that the guide be used like vision to promote and/or establish new behaviors. In addition to response transfer, then, it is argued that with long-term users a second criteria for spontaneous or perceptual usage should be the observation of the emergence of new behaviors, behaviors that would otherwise not be observed in the development of the normal congenitally blind infant. Currently, a study is in progress in which specific questions will be asked along these lines. (Abstract by C. Hoyt)
Comment In this fascinating and thought-provoking study, the authors suggest the periodic use of a sonar device by blind infants will not only enhance their short-term motor development but may, in fact, alter permanently their long-term behavioral and motor development. This is based upon their own preliminary short-term study of ten infants tested from five months to 25 months with various causes of congenital blindness. It is important to note that one of the major methodoIogy problems in this paper and in all papers addressing the