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Ito hypomelanosis and moyamoya disease
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Ito Hypomelanosis and Moyamoya Disease Bernard P. Echenne, M D * , Nicolas Leboucq, MD*, and V~ronique H u m b e r t c l a u d e , M D *
A transient ischemic attack with nearly complete progressive recovery occurred at age 20 months in a girl with Ito's hypomelanosis. Outcome included mental deficiency and behavioral difficulties requiring special education, but without recurrence of ischemic attack. The angiographic investigation performed at 9 years of age disclosed bilateral stenosis of the internal carotid artery characteristic of moyamoya disease. This association has not been reported previously. Echenne BP, Leboucq N, Humbertclaude V. Ito hypomelanosis and moyamoya disease. Pediatr Neurol 1995;13: 169-171.
Introduction Ito hypomelanosis (IH) is a neurocutaneous syndrome characterized by bizarre macular hypopigmented whorls, streaks, and patches, which appear frequently on the trunk, occasionally on the extremities, and seldom on the face. These skin manifestations, which are not preceded by inflammatory or degenerative changes, can be present at birth or develop during childhood. McKusick's catalogue of inherited diseases lists IH as an autosomal dominant disorder, although evidence for this mode of inheritance, or indeed for any genetic etiology, is inconclusive [1,2]. A wide variation of neurologic involvement is reported in IH: mental deficiency, epilepsy, autistic behavior, macrocephaly, and microcephaly are the most frequently observed abnormalities. The frequency of association of central nervous system involvement with IH varies among
From the Departments of *Neuropediatrics and *Neuroradiology; Gui de Chauliac Hospital; Montpellier, France.
© 1995 by Elsevier Science Inc. • 0887-8994/95/$9.50 SSDI 0887-8994(95)00113-T
reports from 40 to 100% [1-4]. To our knowledge, the association of moyamoya disease and IH has not yet been reported.
Case Report Our female patient was born after an uneventful first pregnancy and delivery. Her psychomotor development was initially normal. At 8 months of age, hypopigmented cutaneous areas appeared in a bilateral linear distribution on the thighs and buttocks, and a splashing aspect on the lateral side of the thorax. The diagnosis of IH was made after cutaneous biopsy. At age 20 months, a flaccid left hemiparesis of progressive onset, completed in a few days, was observed, with hypomotility and loss of muscle tone. There was no demonstrated precipitating factor nor associated signs (e.g., headaches, transient involuntary movement, visual or consciousness disturbances). The hemiparesis remained unilateral and subsided spontaneously within a few months with nearly complete normalization of muscle tone. Cerebral computed tomography (CT) disclosed bilateral temporal hypodensities. The diagnosis of encephalitis was suspected but not confirmed by clinical and laboratory examination. The girl remained symptom-free until 9 years of age. She did not experience headaches, visual disturbances, or transient ischemic attacks but did develop marked mental retardation (IQ < 50) associated with hyperactivity and aggressiveness and required special education. Cerebral CT performed at 6 and 9 years of age disclosed extensive unchanged low density areas at the frontal and temporal level bilaterally. At 9 years of age, a thrombophlebitis occurred as a consequence of femur fracture with favorable outcome. Clinical examination revealed no motor disturbance except for the preexistent slight decrease of muscle tone of the left arm and hand. Head circumference was small (50 cm, 10th percentile) and there was obvious mental deficiency (IQ < 50 as measured on the Welcher Intelligence Scale for Children-Revised). The cutaneous abnormalities consisted of small hypopigmented areas on the left lateral side of the thorax, which did not cross the midline. Very small linear hypopigmented lesions were also observed bilaterally on the upper thighs. Doppler study of cervical vessels was normal, but transcranial Doppler sonography disclosed no flow at sylvian or anterior cerebral artery level. Cerebral magnetic resonance imaging (MRI) disclosed highly intense cortical and periventricular signal areas predominating at the frontal and temporal level (Fig 1). Cerebral angiography revealed the characteristic findings of moyamoya disease [5]: stenosis at the terminations of the internal carotid artery and of the proximal portions of the anterior and middle cerebral arteries (Fig 2), an abnormal network of blood vessels in the neighboring areas seen during the arterial phase of cerebral angiography, and the bilateral presence of these abnormalities (stage IIIb [5]). Biological investigations were normal (coagulation tests, antithrombin III S and C protein levels, platelet count, karyotype).
Discussion In our patient, moyamoya disease was diagnosed using cerebral angiography. The persistent discrete motor paral-
Communications should be addressed to: Prof. B. Echenne; Neuropediatrics Department; Gui de Chauliac Hospital; 34295 Montpellier Cedex 5, France. Received September 22, 1994; accepted May 16, 1995.
Echenne et al: Ito Hypomelanosis
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Figure 1. T2-weighted MRI sequences: multiple areas of high signal on both cerebral hemispheres. [MR Max 0.5 Tesla (General Electrics); TR: 2,000 ms, TE: 40 ms, 80 ms, and 120 ms; matrix 160~256;field: 25 cm; 2 ex(NrX:2)].
ysis without transient ischemic attack recurrences (TIA), associated with marked intellectual impairment, corresponds to the " n o n - T I A " type of moyamoya disease described by Fukuyama and Umezu [5]. There is a striking discrepancy between the angiographic or MRI abnormalities and the clinical status of the patient whose motor abilities are nearly normal. This is a well-known finding in moyamoya disease where a poor correlation exists between clinical course and cerebral angiographic stage
progress [5]. Moyamoya disease is a vasoocclusive disease of the intracranial circulation seldom seen in Western countries. The condition is characterized by a progressive bilateral stenosis or occlusion of the distal part of the internal carotid arteries, and not infrequently of the proximal anterior and middle cerebral arteries. The disease commonly presents with ischemic cerebrovascular episodes due to impaired circulation, with recurrence of neurologic deficits and intellectual regression. On histologic examination, prominent features are fibrocellular thickening of the intima and enhanced angiogenesis. The pathogenesis is unknown. The incidence seems to be sporadic, with occasionally familial occurrence [6]. Various cases have been described presenting a moyamoya-like appearance ( " q u a s i - m o y a m o y a " ) due to known causes. These situations are heterogeneous and correspond to unilateral arterial occlusion: pyogenic meningitis, tuberculous meningitis, leptospirosis, sickle-cell anemia, Fanconi's anemia, Down syndrome, congenital heart disease, primary pulmonary hypertension, radiation therapy, homocystinuria, mitochondrial encephalomyopathy, periarteritis nodosa. This condition has also been described occasionally in neurocutaneous syndromes: Von Recklinghausen's disease, tuberous sclerosis, encephalotrigeminal angiomatosis, incontinentia pigmenti [6-9]. In these cases, unilateral arterial occlusion is present most often, but bilateral occlusion predominating on one side may occur. However, bilateral arterial cerebral occlusion has not been reported in IH. Recent studies emphasize the frequency of neurologic symptoms, particularly psychomotor retardation and seizures [2,4], but the only cranial CT and MRI abnormalities reported were focal or generalized cerebral atrophy, ventricular dysplasia, porencephaly, or abnormalities of neuronal migration [4,10]. The review of 59 cases in the literature by Griebel et al. [2[ and the important personal series of PascualCastroviejo et al. [4] do not mention arterial occlusion of moyamoya disease on MRI or angiographic examination. In our patient, the coexistence of IH and moyamoya disease may be coincidental; on the other hand, the occurrence of a posttraumatic leg thrombophlebitis could be the consequence of an unrecognized biological deficit affecting coagulation and leading to venous and arterial occlusion. It seems likely, however, that IH and moyamoya disease are related, as are other neurocutaneous syndromes, and we propose that IH be added to the list of rare known causes of moyamoya disease.
References
Figure 2. Right humeral angiography: occlusion of the middle cerebral arteries with marked irregularity with narrowing and slight fusiform dilatation of the vessels. Development of the collaterals is characteristic of moyamoya disease.
170 PEDIATRICNEUROLOGY Vol. 13 No. 2
[1] Hara M, SaitoK, YajimaK, et al. Clinico-pathologicalstudy on hypomelanosisof Ito. A neurocutaneous syndrome(abstract). Brain Dev 1987;9:141. [2] Griebel V, Kr~igelohMann I, Michaelis R. Hypomelanosisof Ito. Report of four cases and survey of the literature. Neuropediatrics 1989;20:234-7.
[3] Ortonne JP, Coiffet J, Floret D. Hypom61anose de Ito: A propos d'un cas. Ann Dermatol Venereol 1979;106:47-50. [4] Pascual.Castroviejo I, Lopez-Rodriguez L, De la Cruz Medina M, Salamanca-Maesso C, Roche Herrero C. Hypomelanosis of Ito. Neurological complications in 34 cases. Can J Neurol Sci 1988;15:124-9. [5] Fukuyama Y, Umezu R. Clinical and cerebral angiographic evolutions of idiopathic progressive occlusive disease of the circle of Willis ("moyarnoya" disease) in children. Brain Dev 1985;7:21-37. [6] Gordon N, Isler W. Childhood moyamoya disease. Dev Med Child Neurol 1989;31:98-107.
[7] Levisolm PM, Mikhael MA, Rothman SM. Cerebrovascular changes in neurofibromatosis. Dev Med Child Neurol 1978;20:789-93. [8] Tresher W. Ischemic stroke syndromes in childhood. Pediatr Ann 1992;21:375-83. [9] PeHegrino RJ, Shah AT. Vascular occlusion associated with incontinentia pigmenti. Pediatr Neurol 1994;10:73-4. [10] Ross DL, Liwnicz BH, Chun RW, Gilbert E. Hypomelanosis of Ito (incontinentia pigmenti achromians). A clinicopathological study: macrocephaly and gray matter heterotopias. Neurology 1982;32:1013-6.
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Ito Hypomelanosis and Moyamoya Disease Bernard P. Echenne, M D * , Nicolas Leboucq, MD*, and V~ronique H u m b e r t c l a u d e , M D *
A transient ischemic attack with nearly complete progressive recovery occurred at age 20 months in a girl with Ito's hypomelanosis. Outcome included mental deficiency and behavioral difficulties requiring special education, but without recurrence of ischemic attack. The angiographic investigation performed at 9 years of age disclosed bilateral stenosis of the internal carotid artery characteristic of moyamoya disease. This association has not been reported previously. Echenne BP, Leboucq N, Humbertclaude V. Ito hypomelanosis and moyamoya disease. Pediatr Neurol 1995;13: 169-171.
Introduction Ito hypomelanosis (IH) is a neurocutaneous syndrome characterized by bizarre macular hypopigmented whorls, streaks, and patches, which appear frequently on the trunk, occasionally on the extremities, and seldom on the face. These skin manifestations, which are not preceded by inflammatory or degenerative changes, can be present at birth or develop during childhood. McKusick's catalogue of inherited diseases lists IH as an autosomal dominant disorder, although evidence for this mode of inheritance, or indeed for any genetic etiology, is inconclusive [1,2]. A wide variation of neurologic involvement is reported in IH: mental deficiency, epilepsy, autistic behavior, macrocephaly, and microcephaly are the most frequently observed abnormalities. The frequency of association of central nervous system involvement with IH varies among
From the Departments of *Neuropediatrics and *Neuroradiology; Gui de Chauliac Hospital; Montpellier, France.
© 1995 by Elsevier Science Inc. • 0887-8994/95/$9.50 SSDI 0887-8994(95)00113-T
reports from 40 to 100% [1-4]. To our knowledge, the association of moyamoya disease and IH has not yet been reported.
Case Report Our female patient was born after an uneventful first pregnancy and delivery. Her psychomotor development was initially normal. At 8 months of age, hypopigmented cutaneous areas appeared in a bilateral linear distribution on the thighs and buttocks, and a splashing aspect on the lateral side of the thorax. The diagnosis of IH was made after cutaneous biopsy. At age 20 months, a flaccid left hemiparesis of progressive onset, completed in a few days, was observed, with hypomotility and loss of muscle tone. There was no demonstrated precipitating factor nor associated signs (e.g., headaches, transient involuntary movement, visual or consciousness disturbances). The hemiparesis remained unilateral and subsided spontaneously within a few months with nearly complete normalization of muscle tone. Cerebral computed tomography (CT) disclosed bilateral temporal hypodensities. The diagnosis of encephalitis was suspected but not confirmed by clinical and laboratory examination. The girl remained symptom-free until 9 years of age. She did not experience headaches, visual disturbances, or transient ischemic attacks but did develop marked mental retardation (IQ < 50) associated with hyperactivity and aggressiveness and required special education. Cerebral CT performed at 6 and 9 years of age disclosed extensive unchanged low density areas at the frontal and temporal level bilaterally. At 9 years of age, a thrombophlebitis occurred as a consequence of femur fracture with favorable outcome. Clinical examination revealed no motor disturbance except for the preexistent slight decrease of muscle tone of the left arm and hand. Head circumference was small (50 cm, 10th percentile) and there was obvious mental deficiency (IQ < 50 as measured on the Welcher Intelligence Scale for Children-Revised). The cutaneous abnormalities consisted of small hypopigmented areas on the left lateral side of the thorax, which did not cross the midline. Very small linear hypopigmented lesions were also observed bilaterally on the upper thighs. Doppler study of cervical vessels was normal, but transcranial Doppler sonography disclosed no flow at sylvian or anterior cerebral artery level. Cerebral magnetic resonance imaging (MRI) disclosed highly intense cortical and periventricular signal areas predominating at the frontal and temporal level (Fig 1). Cerebral angiography revealed the characteristic findings of moyamoya disease [5]: stenosis at the terminations of the internal carotid artery and of the proximal portions of the anterior and middle cerebral arteries (Fig 2), an abnormal network of blood vessels in the neighboring areas seen during the arterial phase of cerebral angiography, and the bilateral presence of these abnormalities (stage IIIb [5]). Biological investigations were normal (coagulation tests, antithrombin III S and C protein levels, platelet count, karyotype).
Discussion In our patient, moyamoya disease was diagnosed using cerebral angiography. The persistent discrete motor paral-
Communications should be addressed to: Prof. B. Echenne; Neuropediatrics Department; Gui de Chauliac Hospital; 34295 Montpellier Cedex 5, France. Received September 22, 1994; accepted May 16, 1995.
Echenne et al: Ito Hypomelanosis
169
Figure 1. T2-weighted MRI sequences: multiple areas of high signal on both cerebral hemispheres. [MR Max 0.5 Tesla (General Electrics); TR: 2,000 ms, TE: 40 ms, 80 ms, and 120 ms; matrix 160~256;field: 25 cm; 2 ex(NrX:2)].
ysis without transient ischemic attack recurrences (TIA), associated with marked intellectual impairment, corresponds to the " n o n - T I A " type of moyamoya disease described by Fukuyama and Umezu [5]. There is a striking discrepancy between the angiographic or MRI abnormalities and the clinical status of the patient whose motor abilities are nearly normal. This is a well-known finding in moyamoya disease where a poor correlation exists between clinical course and cerebral angiographic stage
progress [5]. Moyamoya disease is a vasoocclusive disease of the intracranial circulation seldom seen in Western countries. The condition is characterized by a progressive bilateral stenosis or occlusion of the distal part of the internal carotid arteries, and not infrequently of the proximal anterior and middle cerebral arteries. The disease commonly presents with ischemic cerebrovascular episodes due to impaired circulation, with recurrence of neurologic deficits and intellectual regression. On histologic examination, prominent features are fibrocellular thickening of the intima and enhanced angiogenesis. The pathogenesis is unknown. The incidence seems to be sporadic, with occasionally familial occurrence [6]. Various cases have been described presenting a moyamoya-like appearance ( " q u a s i - m o y a m o y a " ) due to known causes. These situations are heterogeneous and correspond to unilateral arterial occlusion: pyogenic meningitis, tuberculous meningitis, leptospirosis, sickle-cell anemia, Fanconi's anemia, Down syndrome, congenital heart disease, primary pulmonary hypertension, radiation therapy, homocystinuria, mitochondrial encephalomyopathy, periarteritis nodosa. This condition has also been described occasionally in neurocutaneous syndromes: Von Recklinghausen's disease, tuberous sclerosis, encephalotrigeminal angiomatosis, incontinentia pigmenti [6-9]. In these cases, unilateral arterial occlusion is present most often, but bilateral occlusion predominating on one side may occur. However, bilateral arterial cerebral occlusion has not been reported in IH. Recent studies emphasize the frequency of neurologic symptoms, particularly psychomotor retardation and seizures [2,4], but the only cranial CT and MRI abnormalities reported were focal or generalized cerebral atrophy, ventricular dysplasia, porencephaly, or abnormalities of neuronal migration [4,10]. The review of 59 cases in the literature by Griebel et al. [2[ and the important personal series of PascualCastroviejo et al. [4] do not mention arterial occlusion of moyamoya disease on MRI or angiographic examination. In our patient, the coexistence of IH and moyamoya disease may be coincidental; on the other hand, the occurrence of a posttraumatic leg thrombophlebitis could be the consequence of an unrecognized biological deficit affecting coagulation and leading to venous and arterial occlusion. It seems likely, however, that IH and moyamoya disease are related, as are other neurocutaneous syndromes, and we propose that IH be added to the list of rare known causes of moyamoya disease.
References
Figure 2. Right humeral angiography: occlusion of the middle cerebral arteries with marked irregularity with narrowing and slight fusiform dilatation of the vessels. Development of the collaterals is characteristic of moyamoya disease.
170 PEDIATRICNEUROLOGY Vol. 13 No. 2
[1] Hara M, SaitoK, YajimaK, et al. Clinico-pathologicalstudy on hypomelanosisof Ito. A neurocutaneous syndrome(abstract). Brain Dev 1987;9:141. [2] Griebel V, Kr~igelohMann I, Michaelis R. Hypomelanosisof Ito. Report of four cases and survey of the literature. Neuropediatrics 1989;20:234-7.
[3] Ortonne JP, Coiffet J, Floret D. Hypom61anose de Ito: A propos d'un cas. Ann Dermatol Venereol 1979;106:47-50. [4] Pascual.Castroviejo I, Lopez-Rodriguez L, De la Cruz Medina M, Salamanca-Maesso C, Roche Herrero C. Hypomelanosis of Ito. Neurological complications in 34 cases. Can J Neurol Sci 1988;15:124-9. [5] Fukuyama Y, Umezu R. Clinical and cerebral angiographic evolutions of idiopathic progressive occlusive disease of the circle of Willis ("moyarnoya" disease) in children. Brain Dev 1985;7:21-37. [6] Gordon N, Isler W. Childhood moyamoya disease. Dev Med Child Neurol 1989;31:98-107.
[7] Levisolm PM, Mikhael MA, Rothman SM. Cerebrovascular changes in neurofibromatosis. Dev Med Child Neurol 1978;20:789-93. [8] Tresher W. Ischemic stroke syndromes in childhood. Pediatr Ann 1992;21:375-83. [9] PeHegrino RJ, Shah AT. Vascular occlusion associated with incontinentia pigmenti. Pediatr Neurol 1994;10:73-4. [10] Ross DL, Liwnicz BH, Chun RW, Gilbert E. Hypomelanosis of Ito (incontinentia pigmenti achromians). A clinicopathological study: macrocephaly and gray matter heterotopias. Neurology 1982;32:1013-6.
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