Journal of Korean Medical Science Vol. 8, No. 6, 476-481 December 1993 Delayed-onset Focal Dystonia After Diffuse Cerebral Hypoxia — Two Case Reports — Young Chul Choi, M.D., Myung Sik Lee, M.D., Il Saing Choi, M.D. Department of Neurology, Youngdong Severance Hospital, Yonsei University College of Medicine, Seoul, Korea The delayed-onset. focal dystonia is a rare sequela of cerebrovascular dis- ease or diffuse cerebral hypoxic damage. The responsible lesion sites for the dystonia are variable and the pathogenesis is uncertain. We describe two children with delayed-onset focal dystonia as a complica- tion of perinatal anoxia. The intervals between hypoxic insult and onset of dystonia were 6 years in one and 3 in the other case. Our patients did not have a focal lesion; one had scattered white matter lesion and the other had a diffuse frontoparietal atrophy. Delayed-onset dystonia after perinatal anox- ia can be also caused by non-focal lesion such as diffuse frontoparietal atro- phy or cerebral white matter lesion with long interval delay. ’ Key Words: Delayed-onset dystonia, perinatal anoxia INTRODUCTION Dystonia is characterized by sustained muscle contraction, which leads to abnormal and/or twisting and repetitive movements(Fahn, 1988). Since the first description by Hammond in. -1871, delayed-onset dystonia is a rare but well known sequela of diffuse cerebral hypoxic dam- age(Burke et al, 1980;Marsden et al, 1985; Petti- grew and Jancovic, 1985; Saint-Hilaire et al, 1991) or cerebrovascular disease(Traub and Ridley, 1982; Demierre and Rondot, 1983; Russo, 1983; Obeso et al, 1984; Chiang and Lu, 1990). It can occur immediately after a brain damage, but more frequently it develops after a variable pe- riod(Russo, 1983; Marsden et al, 1985; Pettigrew and Jancovic, 1985). Caudate nucleus, lentiform nucleus, thalamus, internal capsule, or variable combinations of them have been reported as the responsible sites for delayed-onset dystonia, es- Address for correspondence: Young Chul Choi, Depart- ment of Neurology, Yongdong Severance Hospital, Yon- sei University, College of Medicine, Seoul, Korea(Tel.: 569-0110 Ext. 2230). posture . 476 pecially in stroke patients(Marsden et al, 1985; Pettigrew and Jancovic, 1985). However, Glatt and Nausieda(1984) had reported 2 patients with le- sion outside the extrapyramidal system and there were several reports of delayed-onset dystonia caused by. perinatal anoxia without focal basal ganglia lesion(Table 1). The pathologic process responsible for the dysto- nia during the initial recovery period is unknown. Burke et al.(1980) have hypothesized that the neu- ronal regeneration with brain maturation is respon- sible for the delayed-onset. Some authers have compared the interval and frequency of delayed- onset dystonia in patients of perinatal anoxia and ~ stroke and they concentrated only on the age of hypoxic injury deciding the duration of delay in spite of the differences of etiology(Pettigrew and Jancovic, 1985). We present two patients with delayed-onset focal dystonia after perinatal anoxia and review the re- lated literature. CASE REPORTS Patient 1 An 8-year-old boy was referred due to dystonic posture in the left arm for 2 years. He was a proa- Delayed-onset dystonia 4 477 Table 1. Clinical characteristics and anatomical lesion in dystonic patients reported in the literature after perinatal anox- ia and childhood asphyxia. Reference Age at Ageof Duration Site of* insult onset of delay dystonia Burke birth 7 7yr Lt U/E (1980) birth 14 14yr Rt U/E birth 13 13yr Lt arm birth fe) Qyr Rt U/E birth 6 6.5yr Lt hemi. Pettigrew birth 29 29yr Lt hemi. (1985) birth 2 2yr Rt hemi. birth 32 32yr Lt hemi. Marsden birth 4 Ayr Rt hemi. (1985) birth 1 tyr Lt hemi. Saint Hilaire birth 5 5yr Lt hand (1991) birth 8 8yr Lt hemi. birth 15 15yr Lt hemi. birth 9 Qyr Rt arm birth 14 14yr Rt arm birth 14 14yr Rt arm birth 13 13yr Neck birth DB 13yr Rt arm birth 21 21yr Face birth 17 17yr Neck 3yr 9 6yr Both arm 18mon 17 .16yr ~Face Presentcase birth 6 6yr Lt U/E birth 3 3yr Lt L/E uct of a full-term pregnancy and normal delivery. Severe jaundice and cyanotic apnea developed in the early neonatal period and he received inten- sive treatment for 3 weeks in the hospital. Devel- - opmental milestones were normal until the age of four years. Thereafter, he had a frequent partial seizure. He slowly developed walking difficulty and clumsiness in the left arm. At the age of six, he developed definite dystonic posture of the left upper extremity which was intensified by standing or walking. This consisted of abduction of the shoulder, flexion and external rotation of the elbow and wrist with flexion of the metacarpophalangeal joints and extension of the interphalangeal joints (Fig.1). There was no family history of metabolic or degenerative neurologic disease and no medica- tion history such as neuroleptics. On examination, he had a mild left hemiparesis and muscle wasting. Deep tendon reflexes were hyperactive on the left side. Cranial nerve tests were normal. Cerebellar function revealed no abnormality. Deep and superficial senses were normal. There was no Kayser-Fleischer ring. Normal and negative tests included complete blood count, urinalysis, elec- trolyte, rénal function tests and serum ceruloplas- Etiology Anatomical site & pathology Perinatal anoxia Rt cerebral hemiatrophy Perinatal anoxia Normal Perinatal anoxia Normal Perinatal anoxia Not obtained Perinatal anoxia Normal Perinatal anoxia Rt cerebral hemiatrophy,arachnoid cyst Perinatal anoxia Lt cerebral hemiatrophy,porencephalic Perinatal anoxia Rt putamen Perinatal anoxia Lt cerebral hemiatrophy Perinatal anoxia Rt cerebral hemiatrophy Perinatal anoxia Normal Perinatal anoxia Rt hemiatrophy Perinatal’ anoxia Normal Perinatal anoxia Normal Perinatal anoxia . Normal Perinatal anoxia Normal Perinatal anoxia Normal Perinatal anoxia Bilateral basal ganglia Perinatal anoxia .Normal Perinatal anoxia Cerebellar atrophy Asphyxia Normal Asphyxia Normal Perinatal anoxia Rt frontoparietal atrophy Perinatal anoxia White matter lesion min. But liver enzymes(SGOT/SGOP) were elevat- ed due to hepatitis B virus infection. An electroen- cephalogram showed intermittent bilateral sharp waves at the parieto-occipital region. The comput- ed tomography scan of the brain showed right frontoparietal atrophy(Fig. 2). The frequency of the seizure attacks was reduced markedly after car- bamazepine . administration. There were no changes in the dystonic movement of the left hand with adminstration of trinexyphenidyl. Patient 2 A 9-years-old girl was referred due to walking d- ifficulty for 6 years. The pregnancy was normal and full-term, but delivery was complicated by amniotic fluid aspiration. Developmental milestones were normal until the age of three years. At the age of 3, she developed a spontaneous and action-induced dystonic pos- ture in the left foot. It started gradually and pro- gressed to produce plantar flexion of the left foot during sitting position in a chair(Fig. 3) which was aggravated by walking. There was no family histo- ry of metabolic or degenerative neurologic dis- ease and no medication history such as neurolep- 478 Fig. 1. The dystonic movement of left arm in patient 1(A) intensified by standing up(B). Y. -C. Choi, M. -S. Lee, I. -S. Choi tics. On examination, her mental function was nor- mal. There was no motor weakness. Cranial n- erves were normal. Cerebellar function test was normal. A slit-lamp examination revealed no Kayser- Fleisher ring. Complete blood count, urinalysis, serum electrolytes, renal function test were normal. Liver function tests and seurm ceruloplas- min were normal. The MRI of the brain showed s- cattered high signal intensity in the white matter, e- specially at the bilateral occipital and parietal area (Fig. 4). Mild improvement of dystonic posture was noted after an administration of clonazepam. DISCUSSION Delayed-onset dystonia is a rare sequela of cerebral hypoxic insult(Dooling and Adams, 1975) such as perinatal anoxia(Burke et al, 1980; Mars- den et al, 1985; Pettigrew and Jancovic, 1985; Saint-Hilaire et al, 1991) or cerebrovascular dis- ease(Traub and Ridley, 1982; Demierre and Ron- dot, 1983;Russo, 1983; Obeso et al, 1984). It may also develop as a sequela of many other disorders such as; trauma(Andrew et al, 1982; Brett and Hoart, 1981; Krauss et al, 1992), tumor(Marsden et al, 1985; Glatt and Nausieda, 1984; Narbona et al, 1984), infection(Dooling and Adams, 1975), vasculitis and SLE( Anegawa et al,1986; Daras et al, 1988). It can occur immediately after hemiple- gia, but more frequently much later with the recov- ery from hemiplegia. In our series, two patients de- veloped dystonia after perinatal hypoxia. The la- tency between brain hypoxic insults and the onset of dystonia were 6 years and 3 years. The anatomical basis and pathogenesis of de- Fig. 2. A brain CT of Patient 1 revealed diffuse frontoparietal atrophy. Delayed-onset dystonia . 479 Fig. 4. A MRI of the brain of patient 2 showed abnormal high signal intensity in bilateral occipi- tal and parietal deep white matter(repetition time, 3000 msec; echo time, 80 msec). layed-onset dystonia is uncertain. Mitchell(1974) has suggested that the delay in the onset of hemi- chorea or athetosis following hemiplegia was caused byy progressive changes in the original brain lesion. Burke(1980) has hypothesized that the mechanism of delayed-onset dystonia occur- ring a year or more after the insult may be due to aberrant neuronal sprouting with brain maturation. Pettrigrew and Jankovic(1985) studied 22 patients of delayed-onset dystonia following variable caus- es. They found that the mean interval in the seven patients who had brain lesions below the age of 7 was much longer than the remaining patients above the age of 7, and postulated that the age of the patient at the time of cerebral injury decides the duration of delay after the acute brain damage. However, these hypothesis have limita- tion. Some patients with immediate onset can not be explained by neuronal regeneration. Because if the delayed-onset dystonia is caused by neuronal regeneration with brain maturation, the patients of hypoxic injury at the perinatal and early childhood period would have shorter duration of delay than that of hypoxic injury after early childhood. ae Therefore we reviewed the literature to further characterize the relationship between anatomical 480 lesion site and the latency of delay in perinatal hy- poxia brain damage. 20 cases of delayed-onset dystonia after perinatal anoxia(Burke et al, 1980; Marsden et al, 1985; Pettigrew and Jancovic, 1985: Saint-Hilaire et al, 1991) and 2 cases of de- layed-onset dystonia after early childhood asphyx- ia(Saint-Hilaire et al, 1991)(Table 1) have been re- ported. The intervals between the onset of dysto- nia and perinatal hypoxic brain damage were var- ied from 1 year to 32 years(mean delay: 12.3 years). Dystonia following childhood asphyxia ap- peared 6 years and 16 years after hypoxic insult. After studying our cases and the literature, it be- came clear that the delay of dystonia following perinatal anoxic brain damage is long and there are variety of anatomical lesion sites such as non- focal diffuse cerebral lesion. The pathological lesions in patients of delayed onset dystonia have a variety of anatomical lesion sites. Damage to the neuronal circuit connecting the caudate, putamen, globus pallidus and thala- mus(Pettigrew and Jancovic, 1985; Fross et al, 1987) seems to be responsible for the dystonia fol- lowing cerebrovascular disease. However, it can occur without evidence of striatal lesion(Glatt and Nausieda, 1984) and thalamic degeneration fol- lowing striatal lesion or cortical lesion have also been reported(Oppenhemer, 1967; Dooling and Adams, 1975; Grimes et al, 1982). The respon- sibe pathologic lesions in patients of perinatal anoxia can be diffuse cerebral lesion(Table 1). 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