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Benign Paroxysmal Tonic Upgaze of Childhood A New Syndrome* By Th. Deonna, E. Roulet and H. U. Meyer
Abstract A child with intermittent upward deviation of the eyes starting at 9 months of age, compensating bending forward of the head, nystagmus on attempted downward gaze and a mild gait ataxia is described. The symptoms gradually disappeared between 3 and 4 years of age. Four cases with identical clinical findings have been initially described by Ouvrier in Australia (5) as "benign paroxysmal tonic upgaze of childhood". It is apparently a new syndrome.
Keywords Paroxysmal disorder - Eye movement disorders - Tonic eye deviation - Infantile nystagmus - Childhood ataxia - Infancy
Introduction
Ouvrier and Billson have recently reported (5) four cases of a previously undescribed disorder of eye movements starting in infancy. It consists of sustained intermittent tonic conjugate upward deviation of the eyes with compensative bending forward of the head. On attempted downward gaze, there are down-beating ocular saccades. The horizontal eye movements are preserved and the children have otherwise normal development except sometimes a mild ataxia. The symptoms are relieved by sleep and are exacerbated with fatigue or stress and tend to disappear gradually over the years. We are reporting the history of a 4-year-old child with an identical syndrome to the one described by Ouvrier. Several specialized investigations were undertaken and multiple differential diagnosis were entertained until gradual improvement. The finding of the publication of a similar syndrome convinced us that we were facing a special and new enti-
Because acquired vertical eye movement disorders and ataxia in young children can be observed in various structural abnormalities of brainstem or neurometabolic diseases (4), it is important to recognize syndromes in which similar symptoms can occur with no definable pathology and a self limited regressive course. In addition, this child also had some anomalies of horizontal eye movements and had unexplained sudden falls, as reported in Case 3 of Ouvrier but was not stressed as a possible feature of the disorder.
Case report This boy had anormal development until 9 months of age when brief, intermittent upward deviations of the eyes were noted by the mother. At 10 months of age, she said that they occurred "for very long periods". At 14 months, she noticed also vertical jerks of the eyes with difficulty in looking downwards. He walked alone at 16 months and was said to fall often and to have an unsteady gait. When first examined by us at 21 months of age, he had an intermittent upward deviation of the eyes which lasted hours or days with a compensatory posture of the head tilted chin down. There was a down-beating nystagmus when attempting to look downward with apparent difficulty of gaze in that direction. The horizontal pursuit was not smooth and rapid eye movements were slightly impaired without head-thrust. He walked with a wide and unsteady gait. This remained so for at least a year and could not be described just as an immature gait. Otherwise the overall neurological development was normal for his age. The EEG records during and between the periods of abnormal eye movements were normal. CT-scan, NMR of the head and CSF examination were also normal. Electrolytes, blood gazes and aminoacid screening showed no abnormalities. In the following months, the symptoms continued but were clearly fluctuant and increasing with fatigue and intercurrent illnesses. They were less marked in the morning but not absent. This apparent fluctuation with sleep had not struck us initially until we read Ouvrier's paper, but this was clearly the case on retrospective questioning of the family and on review of videofilms made at different periods of the day. Treatment with acetazolamide (Diamox R) for three and a half months from 21 to 25 months did not bring any visible change in symptoms (8).
ty.
Received March 17, 1990; accepted March 26, 1990 Neuropediatrics 21 (1990) 213-214 © Hippokrates Verlag Stuttgart
* Paper presented at the IVth Congress of the "Socü~te Europeenne de Neurologie Pediatrique", Barcelona, 23-24. 11. 1989
Downloaded by: National University of Singapore. Copyrighted material.
Pediatric Department (Neuropediatric Unit) , CHUV, Lausanne, Switzerland
N europediatrics 21 (1990)
Over the next two years, the symptoms became gradually less marked and the neurological development proceeded entirely normally except for a slight delay in expressive language only. When last seen at 39 months of age, he could run, kick the ball, stop and turn rapidly without evident ataxia, but he was still slightly clumsy. The abnormal eye movements and compensatory head posture had almost disappeared. Since the age of 18 months, this child also had episodes of cyanosis, loss of contact, hypotonia and falls sometimes but not always triggered by an emotional situation. This worried the family very much but we never witnessed similar episodes and initially we were not sure if these were simple breath holding spells. In the most recent spells, emotional triggering factors have been obvious each time.
Discussion This child had an acquired fluctuant, supranuclear disturbance of vertical gaze with a moderate gait ataxia and a gradual spontaneous recovery. The essential clinical findings and course are similar to what Ouvrier and Billson have recently reported as a new syndrome under the title of "Benign paroxysmal tonic upgaze of childhood" (5), and differ from the other known congenital or acquired brainstem disorders where resembling symptoms can be found. In Ouvrier's four cases, symptoms started between 6 and 24 months and were improved by sleep in three of them. One had had a moderate persistent gait ataxia, and one had had intermittent ataxia with fever. All improved during a follow-up of 18 months to 16 years. In addition, our child also had slight difficulties with horizontal gaze and unexplained episodes of unconsciousness and falls which were thought to be breath holding spells but for which the clinical description was atypical and led us to think of atypical brainstem or cerebellar manifestations. Case 3 of Ouvrier and Billson also had bizarre episodes of "collapse to the floor as if he were like jelly". This may be another paroxysmal feature of this syndrome which will need to be looked at in new cases.
Ahn and Hoyt have recently reported three infants with so-called "tonic upgaze in infancy" (1). The disturbance of eye movements is very similar to the cases of Ouvrier and Billson but the onset was much earlier ("from the first month of life"). Downward eye movements were normal and ataxia was not reported in these children. The anomaly of eye movements also increased with fever or fatigue and decreased with sleep. The abnormal signs disappeared in all three cases at the followup from 8 months to 3 years and 6 months. Thus it is possible that this syndrome is the same as the one described by Ouvrier with an earlier age at onsel. Transient disorders of supranuclear vertical eye movements are frequently seen in otherwise healthy newborns, particularly a tendency to downward gaze deviation. This has been described as "transient tonic downward gaze deviation in healthy neonates" (3). In some babies and infants, the downward eye deviation is not constant and sometimes can be triggered by various sensory stimuli (i. e. brisk change of posture) but mainly by a rapid change in illumination (from bright
Th. Deonna et al
to dark light) and is accompanied by a retraction of the upper eye-lid, the so-called eye-popping phenomenon (6). This phenomenon is transitory and disappears gradually completely but can last for several months. One can also conceive that the infants reported by Ahn et al (1) have a closely related maturational phenomenon (in the opposite direction). One of the children described by Ouvrier was improved by levodopa therapy and one child with this syndrome who died accidentally had anormal brain examination. Anatomie, physiologie and metabolie studies in these children have been normal. Because of the fluctuation of the symptoms, the relief by sleep and improvement by l-dopa in one case, Ouvrier proP9sed that a localized insufficiency of neurotransmitter function, operating on the control of the inhibitory and excitatory pathways of supranuclear vertical eye movements, could be responsible. This situation has some analogy with dopa-sensitive dystonia with diurnal fluctuation of symptoms (7) in which intermittent abnormal vertical eye movements have also been reported (2). Further reports will possibly bring some new data on these speculations. It is probable that the syndrome described here is not exceptional as informal discussions with colleagues have suggested to uso We prompt pediatric neurologists to report their experiences with similar or closely related cases, particularly if the relief of symptoms by sleep, response to l-dopa can be confirmed and if abnormalities of horizontal movements and atypical "breath holding speIls" are also being found.
References Ahn,]. C., W. F. Hoyt, C. S. Hoyt: Tonic upgaze in infancy. Arch. Ophthalmol. 107 (1989) 57-58 2 Deonna, T: Dopa-sensitive progressive dystonia of childhood with fluctuations of symptoms. Segawa's syndrome and possible variants. Neuropediatrics 2 (1986) 81-85 3 Hoyt, C. 5., D. K. Monsel, A. A. Weber: Transient supranuclear disturbances of gaze in healthy neonates. Am. J. Ophthalmol. 89 (1980) 708-713 4 Neville, B., G. R. Lake, B. D. Stephens, R. Sanders: A neurovisceral storage disease with vertical supranuclear ophthalmoplegia and its relationship to Niemann-Pick disease. Areport of 9 patients. Brain 96 (19~3) 981
118
Ouvrier, R. A., M. D. Billson: Benign paroxysmal tonic upgaze of childhood.J. ChildNeurol. 3 (1988) 177-180 6 Perez, R. B.: The eye-popping reflex of infants. J. Pediatr. 81 (1972) 885
89
Segawa, M., A. Hosaka, F. Miyagawa, Y. Nomura, H. Imai: Hereditary progressive dystonia with marked diurnal fluctuations. In Adv. Neurol. 14. Fahn, 5., Eldridge, E. (Eds.) 215-233 (1976) 8 Verlooy, P., D. N. Velis: Non-familial periodic ataxia responding to acetazolamide. Clin. Neurol. Neurosurg. 87 (1985) 35-37 7
Th. Deonna, M. D., Ass. Prof Pediatric Department Neuropediatric Unit CHUV CH -1011 Lausanne, Switzerland
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214
Benign Paroxysmal Tonic Upgaze of Childhood A New Syndrome* By Th. Deonna, E. Roulet and H. U. Meyer
Abstract A child with intermittent upward deviation of the eyes starting at 9 months of age, compensating bending forward of the head, nystagmus on attempted downward gaze and a mild gait ataxia is described. The symptoms gradually disappeared between 3 and 4 years of age. Four cases with identical clinical findings have been initially described by Ouvrier in Australia (5) as "benign paroxysmal tonic upgaze of childhood". It is apparently a new syndrome.
Keywords Paroxysmal disorder - Eye movement disorders - Tonic eye deviation - Infantile nystagmus - Childhood ataxia - Infancy
Introduction
Ouvrier and Billson have recently reported (5) four cases of a previously undescribed disorder of eye movements starting in infancy. It consists of sustained intermittent tonic conjugate upward deviation of the eyes with compensative bending forward of the head. On attempted downward gaze, there are down-beating ocular saccades. The horizontal eye movements are preserved and the children have otherwise normal development except sometimes a mild ataxia. The symptoms are relieved by sleep and are exacerbated with fatigue or stress and tend to disappear gradually over the years. We are reporting the history of a 4-year-old child with an identical syndrome to the one described by Ouvrier. Several specialized investigations were undertaken and multiple differential diagnosis were entertained until gradual improvement. The finding of the publication of a similar syndrome convinced us that we were facing a special and new enti-
Because acquired vertical eye movement disorders and ataxia in young children can be observed in various structural abnormalities of brainstem or neurometabolic diseases (4), it is important to recognize syndromes in which similar symptoms can occur with no definable pathology and a self limited regressive course. In addition, this child also had some anomalies of horizontal eye movements and had unexplained sudden falls, as reported in Case 3 of Ouvrier but was not stressed as a possible feature of the disorder.
Case report This boy had anormal development until 9 months of age when brief, intermittent upward deviations of the eyes were noted by the mother. At 10 months of age, she said that they occurred "for very long periods". At 14 months, she noticed also vertical jerks of the eyes with difficulty in looking downwards. He walked alone at 16 months and was said to fall often and to have an unsteady gait. When first examined by us at 21 months of age, he had an intermittent upward deviation of the eyes which lasted hours or days with a compensatory posture of the head tilted chin down. There was a down-beating nystagmus when attempting to look downward with apparent difficulty of gaze in that direction. The horizontal pursuit was not smooth and rapid eye movements were slightly impaired without head-thrust. He walked with a wide and unsteady gait. This remained so for at least a year and could not be described just as an immature gait. Otherwise the overall neurological development was normal for his age. The EEG records during and between the periods of abnormal eye movements were normal. CT-scan, NMR of the head and CSF examination were also normal. Electrolytes, blood gazes and aminoacid screening showed no abnormalities. In the following months, the symptoms continued but were clearly fluctuant and increasing with fatigue and intercurrent illnesses. They were less marked in the morning but not absent. This apparent fluctuation with sleep had not struck us initially until we read Ouvrier's paper, but this was clearly the case on retrospective questioning of the family and on review of videofilms made at different periods of the day. Treatment with acetazolamide (Diamox R) for three and a half months from 21 to 25 months did not bring any visible change in symptoms (8).
ty.
Received March 17, 1990; accepted March 26, 1990 Neuropediatrics 21 (1990) 213-214 © Hippokrates Verlag Stuttgart
* Paper presented at the IVth Congress of the "Socü~te Europeenne de Neurologie Pediatrique", Barcelona, 23-24. 11. 1989
Downloaded by: National University of Singapore. Copyrighted material.
Pediatric Department (Neuropediatric Unit) , CHUV, Lausanne, Switzerland
N europediatrics 21 (1990)
Over the next two years, the symptoms became gradually less marked and the neurological development proceeded entirely normally except for a slight delay in expressive language only. When last seen at 39 months of age, he could run, kick the ball, stop and turn rapidly without evident ataxia, but he was still slightly clumsy. The abnormal eye movements and compensatory head posture had almost disappeared. Since the age of 18 months, this child also had episodes of cyanosis, loss of contact, hypotonia and falls sometimes but not always triggered by an emotional situation. This worried the family very much but we never witnessed similar episodes and initially we were not sure if these were simple breath holding spells. In the most recent spells, emotional triggering factors have been obvious each time.
Discussion This child had an acquired fluctuant, supranuclear disturbance of vertical gaze with a moderate gait ataxia and a gradual spontaneous recovery. The essential clinical findings and course are similar to what Ouvrier and Billson have recently reported as a new syndrome under the title of "Benign paroxysmal tonic upgaze of childhood" (5), and differ from the other known congenital or acquired brainstem disorders where resembling symptoms can be found. In Ouvrier's four cases, symptoms started between 6 and 24 months and were improved by sleep in three of them. One had had a moderate persistent gait ataxia, and one had had intermittent ataxia with fever. All improved during a follow-up of 18 months to 16 years. In addition, our child also had slight difficulties with horizontal gaze and unexplained episodes of unconsciousness and falls which were thought to be breath holding spells but for which the clinical description was atypical and led us to think of atypical brainstem or cerebellar manifestations. Case 3 of Ouvrier and Billson also had bizarre episodes of "collapse to the floor as if he were like jelly". This may be another paroxysmal feature of this syndrome which will need to be looked at in new cases.
Ahn and Hoyt have recently reported three infants with so-called "tonic upgaze in infancy" (1). The disturbance of eye movements is very similar to the cases of Ouvrier and Billson but the onset was much earlier ("from the first month of life"). Downward eye movements were normal and ataxia was not reported in these children. The anomaly of eye movements also increased with fever or fatigue and decreased with sleep. The abnormal signs disappeared in all three cases at the followup from 8 months to 3 years and 6 months. Thus it is possible that this syndrome is the same as the one described by Ouvrier with an earlier age at onsel. Transient disorders of supranuclear vertical eye movements are frequently seen in otherwise healthy newborns, particularly a tendency to downward gaze deviation. This has been described as "transient tonic downward gaze deviation in healthy neonates" (3). In some babies and infants, the downward eye deviation is not constant and sometimes can be triggered by various sensory stimuli (i. e. brisk change of posture) but mainly by a rapid change in illumination (from bright
Th. Deonna et al
to dark light) and is accompanied by a retraction of the upper eye-lid, the so-called eye-popping phenomenon (6). This phenomenon is transitory and disappears gradually completely but can last for several months. One can also conceive that the infants reported by Ahn et al (1) have a closely related maturational phenomenon (in the opposite direction). One of the children described by Ouvrier was improved by levodopa therapy and one child with this syndrome who died accidentally had anormal brain examination. Anatomie, physiologie and metabolie studies in these children have been normal. Because of the fluctuation of the symptoms, the relief by sleep and improvement by l-dopa in one case, Ouvrier proP9sed that a localized insufficiency of neurotransmitter function, operating on the control of the inhibitory and excitatory pathways of supranuclear vertical eye movements, could be responsible. This situation has some analogy with dopa-sensitive dystonia with diurnal fluctuation of symptoms (7) in which intermittent abnormal vertical eye movements have also been reported (2). Further reports will possibly bring some new data on these speculations. It is probable that the syndrome described here is not exceptional as informal discussions with colleagues have suggested to uso We prompt pediatric neurologists to report their experiences with similar or closely related cases, particularly if the relief of symptoms by sleep, response to l-dopa can be confirmed and if abnormalities of horizontal movements and atypical "breath holding speIls" are also being found.
References Ahn,]. C., W. F. Hoyt, C. S. Hoyt: Tonic upgaze in infancy. Arch. Ophthalmol. 107 (1989) 57-58 2 Deonna, T: Dopa-sensitive progressive dystonia of childhood with fluctuations of symptoms. Segawa's syndrome and possible variants. Neuropediatrics 2 (1986) 81-85 3 Hoyt, C. 5., D. K. Monsel, A. A. Weber: Transient supranuclear disturbances of gaze in healthy neonates. Am. J. Ophthalmol. 89 (1980) 708-713 4 Neville, B., G. R. Lake, B. D. Stephens, R. Sanders: A neurovisceral storage disease with vertical supranuclear ophthalmoplegia and its relationship to Niemann-Pick disease. Areport of 9 patients. Brain 96 (19~3) 981
118
Ouvrier, R. A., M. D. Billson: Benign paroxysmal tonic upgaze of childhood.J. ChildNeurol. 3 (1988) 177-180 6 Perez, R. B.: The eye-popping reflex of infants. J. Pediatr. 81 (1972) 885
89
Segawa, M., A. Hosaka, F. Miyagawa, Y. Nomura, H. Imai: Hereditary progressive dystonia with marked diurnal fluctuations. In Adv. Neurol. 14. Fahn, 5., Eldridge, E. (Eds.) 215-233 (1976) 8 Verlooy, P., D. N. Velis: Non-familial periodic ataxia responding to acetazolamide. Clin. Neurol. Neurosurg. 87 (1985) 35-37 7
Th. Deonna, M. D., Ass. Prof Pediatric Department Neuropediatric Unit CHUV CH -1011 Lausanne, Switzerland
Downloaded by: National University of Singapore. Copyrighted material.
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