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Arteriovenous malformation in hypomelanosis of Ito
ELSEVIER
Brain& Development 1996; 18:78-80
Short communication
Arteriovenous malformation in hypomelanosis of Ito Elena Urgell~s *, Ignacio Pascual-Castroviejo, Carmen Roche, Jose Luis Hernfindez Moneo,
Miguel Angel Martlnez, Aurelio Vega Paediatric Neurology Service, Hospital Infantil 'La Paz', Universidad Aut6noma de Madrid, Paseo de la Castellana 261, 28046 Madrid, Spain
Received 17 June 1995; accepted 17 September 1995
Hypomelanosis of Ito (HI) is a neurocutaneous syndrome with multisystemic involvement. Its most frequent neurological abnormalities are mental retardation and seizures. EEG, CT and MRI findings are not characteristic enough to be diagnostic. In this report, we describe a patient with typical cutaneous lesions of HI and an intracraniai arteriovenous malformation (AVM), which has not been previously reported. Keywords: Hypomelanosis of Ito; Neurocutaneous syndrome; Neurological abnormalities; Arteriovenous malformation
1. I N T R O D U C T I O N Hypomelanosis of Ito (HI) is the third most frequent neurocutaneous disorder, surpassed only by neurofibromatosis type 1 (NF-1) and tuberous sclerosis (TS) [1,2]. It is a systemic disorder, with associated lesions in up to 94% of cases [3]. The cutaneous lesions are typically hypopigmented areas with irregular borders, streaks, whorls or patches, more evident on a hyperpigmented skin or by examination under the UV light of a Woods lamp [2]. These areas show a reduction in the number of melanocytes and in the size and number of melanosomes [1,2]. There are other cutaneous lesions in about 38% of the cases, most commonly caf6 au lait spots, cuffs marmorata, angiomatous nevi, nevus of Ota, mongolian blue spot and heterochromia of the iris or hair, diffuse alopecia and trichorrhexis [1,3]. More than 60% of cases show clinical, radiological or histological abnormalities of the central nervous system (CNS) [1-3]. We report a patient with skin lesions of the type of nevus of Ito associated with a midfacial flat angioma and an intracranial arteriovenous malformation, an association not previously described in the literature.
2. C A S E R E P O R T The child was the sixth son of a healthy non-consanguineous couple. Severe polyhydramnios and fetal macrosomy were detected during pregnancy. He was born in cephalic presentation in
* Corresponding author, C / Melchor Fern~ndez Almagro, 19-12 D, 28029 Madrid, Spain. 0387-7604/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI 0387-7604(95)00114-X
the 37th week of pregnancy, weighing 3680 g and his Apgar scores were 4 at 1 min and 9 at 5 rain, requiring resuscitation with intermittent positive pressure of oxygen (IPPO2). Polyhydramnios was confirmed at delivery. On the ninth day of life tachycardia, hyperdynamic beats and mild cyanosis were detected and the patient was referred to our hospital with the diagnosis of congenital heart disease. Upon arrival, the patient had right ventricular overload with an increase in lung vascularization. Cranial ultrasound detected an arteriovenous malformation (AVM), and CT of the brain revealed a communication between the AVM and the left middle cerebral artery, with an increase of the size of lateral and upper longitudinal venous sinuses and atrophy of the left hemisphere. Conventional angiography showed communication of the AVM with left middle cerebral, left anterior cerebral, left vertebral, posterior communicating and anterior communicating arteries as well as vascularization from the contralateral side (Fig. 1). On the 18th day of life, presurgical embolization of the AVM was performed under angiographic control. The surgical procedure included removal of the malformation through a left frontotemporoparietal approach and implantation of an external ventricular drain. Following surgery the patient developed irritability and tonic seizures, and a postoperative CT showed bleeding in all ventricles and involved the left caudate nucleus with incipient ventricular dilatation, and a left epidural hematoma that required surgical evacuation. On the 36th day of life, EEG showed moderate low voltage activity with slightly irregular waves over the left hemisphere. On the 52nd day of life the patient was alert and a moderate flexion of the right upper extremity was the only sign of focal neurological abnormality. At 8 months of age the patient was referred to us because of seizures. His parents described brisk intermittent movements first
E. UrgellOs et al. / Brain & Development 1996; 1 8 : 7 8 - 8 0
79
pharmacological treatment and the hypsarrhythmia resolved at 9 months of age, but at present the 12-month-old child suffers tonic seizures unresponsive to medication and the EEG shows pathologic activity in the left frontoparietotemporal region.
3. D I S C U S S I O N
Fig. 1. Left carotid arteriogram showing the arteriovenous malformation.
detected 10 days earlier and occurring daily since. Physical examination showed psychomotor retardation - the patient was unable to support his head, had inconstant attention to the environment and displayed poor mobilization of the right side of the body. The right upper extremity was hypertonic with halfflexed fingers and adduction of the thumb. During the physical examination the patient showed infantile spasms. He also had a midfacial flat angioma and several hypopigmented areas (two of 1.5 and 3 cm diameter on his right abdomen, not extending across the midline, one of 1.5 cm diameter over the left scrotum and a larger one over the medial side of the left thigh with a radicular pattern). These lesions were more evident under a Woods lamp. EEG showed hypsarrhythmia. MRI revealed ventriculomegaly, more severe on the left, with multiple porencephalic periventricular cavities, cortical atrophy and subcortical leukomalacia (Fig. 2). Seizures were initially well controlled with
Neurological abnormalities are reported in 40-94% of the cases of HI. This wide range of incidence is related in part to different origins of the series from dermatologic or child neurology units [3]. Severity of neurological abnormalities does not correlate with either extent of cutaneous hypopigmented lesions or microscopic or radiological findings, but it seems to be associated with an early onset of symptoms [2]. The most frequent abnormality is mental retardation, present in more than 60% of the cases and commonly associated with early seizures [3]. There are several types of seizures described in these patients, most frequently infantile spasms or other types of myoclonic epilepsy [2,3]. EEG findings are not pathognomonic, although there is probably a group of patients with early and severe seizures, bizarre EEG abnormalities, poor prognosis and perhaps defects of neuronal migration [4]. Our patient's seizures could be due to his AVM and the lesions developed after surgery, but because they were infantile spasms with hypsarrhythmia, they point to a possible relationship with his HI. Numerous imaging (CT and MR) findings are described in HI including cerebral atrophy, hemimegalencephaly, diffuse hypodensity of white matter, porencephaly, periventricular cystic lesions, disorders of neuronal migration and agenesis of the corpus callosum, although imaging studies occasionally are normal [5,6]. Several chromosomal abnormalities have been described recently in HI karyotypes obtained mainly from cultured fibroblasts, most frequently mosaics for aneuploidy or unbalanced translocations of various chromosomes [7,8]. HI has already been associated with tumors outside the CNS (teratomas or epidermoid cysts of bone) [7] and intracranial tumors (choroid plexus papilloma) [8], but the finding of an intracerebral AVM has not previously been reported. The relationship between both alterations, HI and AVM, is difficult to assess. H1 and AVM are diseases that affect organs of different origin, ectoderm and mesoderm, respectively. The embryological period of maldevelopment is also different. Embryological migration of melanoblasts occurs in the second trimester [9], whereas the abnormal arteriovenous pattern characteristic of an AVM appears in the first trimester during the second stage of the development of cerebral blood vessels, arteries, capillaries and veins with intercommunications [10]. ACKNOWLEDGEMENTS The authors express their thanks to Dr. Harvey B. Sarnat (Seattle) for his help in preparing the manuscript.
REFERENCES
Fig. 2. MRT2 demonstrates ventriculomegaly, multiple porencephalic periventricular cavities, cortical atrophy and subcortical leukomalacia in the left cerebral hemisphere.
1. Hypomelanosis of Ito (Editorial). Lancet 1992; 339: 651-2. 2. Gordon N. Hypomelanosis of Ito (incontinentia pigmenti achromians). Dev Med Child Neurol 1994; 36: 271-4. 3. Pascual-Castroviejo I, L6pez-Rodrlguez 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.
80
E. Urgell~s et al./ Brain & Development 1996; 18:78-80
4. Esquivel EE, Pitt MC, Boyd SG. EEG findings in hypomelanosis of Ito. Neuropediatrics 1991; 22: 216-9. 5. Battistella PA, Peserico A, Bertoli P, Drigo P, Laverda AM, Casara GL. Hypomelanosis of Ito and hemimegalencephaly. Childs Nerv Syst 1990; 6: 421-3. 6. Williams DW, Elster AD. Cranial MR imaging in hypomelanosis of Ito. J Comput Assist Tomogr 1990; 14: 981-3. 7. Ishikawa T, Kanayama M, Sugiyama K, Katoh T, Wada Y. Hypomelanosis of lto associated with benign tumors and chromosomal abnormalities: a neurocutaneous syndrome. Brain Dev (Tokyo) 1985; 7: 45 -9.
8. Steichen-Gersdoff E, TrawSger R, Duba HC, Mayr U, Felber S, Utermann G. Hypomelanosis of Ito in a girl with plexus papilloma and translocation (X;17). Hum Genet 1993; 90: 611-3. 9. Ross DL, Liwnicz BH, Chun RWN, Gilbert E. Hypomelanosis of Ito (incontinentia pigmenti achromians). A clinicopathologic study; macrocephaly and gray matter heterotopias. Neurology 1982; 32: 1013-6. 10. Streeter GL. The developmental alterations in the vascular systems of the brain of the human embryo. Contrib Embryol Carnegie lnst 1918; 8: 5-8.
Brain& Development 1996; 18:78-80
Short communication
Arteriovenous malformation in hypomelanosis of Ito Elena Urgell~s *, Ignacio Pascual-Castroviejo, Carmen Roche, Jose Luis Hernfindez Moneo,
Miguel Angel Martlnez, Aurelio Vega Paediatric Neurology Service, Hospital Infantil 'La Paz', Universidad Aut6noma de Madrid, Paseo de la Castellana 261, 28046 Madrid, Spain
Received 17 June 1995; accepted 17 September 1995
Hypomelanosis of Ito (HI) is a neurocutaneous syndrome with multisystemic involvement. Its most frequent neurological abnormalities are mental retardation and seizures. EEG, CT and MRI findings are not characteristic enough to be diagnostic. In this report, we describe a patient with typical cutaneous lesions of HI and an intracraniai arteriovenous malformation (AVM), which has not been previously reported. Keywords: Hypomelanosis of Ito; Neurocutaneous syndrome; Neurological abnormalities; Arteriovenous malformation
1. I N T R O D U C T I O N Hypomelanosis of Ito (HI) is the third most frequent neurocutaneous disorder, surpassed only by neurofibromatosis type 1 (NF-1) and tuberous sclerosis (TS) [1,2]. It is a systemic disorder, with associated lesions in up to 94% of cases [3]. The cutaneous lesions are typically hypopigmented areas with irregular borders, streaks, whorls or patches, more evident on a hyperpigmented skin or by examination under the UV light of a Woods lamp [2]. These areas show a reduction in the number of melanocytes and in the size and number of melanosomes [1,2]. There are other cutaneous lesions in about 38% of the cases, most commonly caf6 au lait spots, cuffs marmorata, angiomatous nevi, nevus of Ota, mongolian blue spot and heterochromia of the iris or hair, diffuse alopecia and trichorrhexis [1,3]. More than 60% of cases show clinical, radiological or histological abnormalities of the central nervous system (CNS) [1-3]. We report a patient with skin lesions of the type of nevus of Ito associated with a midfacial flat angioma and an intracranial arteriovenous malformation, an association not previously described in the literature.
2. C A S E R E P O R T The child was the sixth son of a healthy non-consanguineous couple. Severe polyhydramnios and fetal macrosomy were detected during pregnancy. He was born in cephalic presentation in
* Corresponding author, C / Melchor Fern~ndez Almagro, 19-12 D, 28029 Madrid, Spain. 0387-7604/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI 0387-7604(95)00114-X
the 37th week of pregnancy, weighing 3680 g and his Apgar scores were 4 at 1 min and 9 at 5 rain, requiring resuscitation with intermittent positive pressure of oxygen (IPPO2). Polyhydramnios was confirmed at delivery. On the ninth day of life tachycardia, hyperdynamic beats and mild cyanosis were detected and the patient was referred to our hospital with the diagnosis of congenital heart disease. Upon arrival, the patient had right ventricular overload with an increase in lung vascularization. Cranial ultrasound detected an arteriovenous malformation (AVM), and CT of the brain revealed a communication between the AVM and the left middle cerebral artery, with an increase of the size of lateral and upper longitudinal venous sinuses and atrophy of the left hemisphere. Conventional angiography showed communication of the AVM with left middle cerebral, left anterior cerebral, left vertebral, posterior communicating and anterior communicating arteries as well as vascularization from the contralateral side (Fig. 1). On the 18th day of life, presurgical embolization of the AVM was performed under angiographic control. The surgical procedure included removal of the malformation through a left frontotemporoparietal approach and implantation of an external ventricular drain. Following surgery the patient developed irritability and tonic seizures, and a postoperative CT showed bleeding in all ventricles and involved the left caudate nucleus with incipient ventricular dilatation, and a left epidural hematoma that required surgical evacuation. On the 36th day of life, EEG showed moderate low voltage activity with slightly irregular waves over the left hemisphere. On the 52nd day of life the patient was alert and a moderate flexion of the right upper extremity was the only sign of focal neurological abnormality. At 8 months of age the patient was referred to us because of seizures. His parents described brisk intermittent movements first
E. UrgellOs et al. / Brain & Development 1996; 1 8 : 7 8 - 8 0
79
pharmacological treatment and the hypsarrhythmia resolved at 9 months of age, but at present the 12-month-old child suffers tonic seizures unresponsive to medication and the EEG shows pathologic activity in the left frontoparietotemporal region.
3. D I S C U S S I O N
Fig. 1. Left carotid arteriogram showing the arteriovenous malformation.
detected 10 days earlier and occurring daily since. Physical examination showed psychomotor retardation - the patient was unable to support his head, had inconstant attention to the environment and displayed poor mobilization of the right side of the body. The right upper extremity was hypertonic with halfflexed fingers and adduction of the thumb. During the physical examination the patient showed infantile spasms. He also had a midfacial flat angioma and several hypopigmented areas (two of 1.5 and 3 cm diameter on his right abdomen, not extending across the midline, one of 1.5 cm diameter over the left scrotum and a larger one over the medial side of the left thigh with a radicular pattern). These lesions were more evident under a Woods lamp. EEG showed hypsarrhythmia. MRI revealed ventriculomegaly, more severe on the left, with multiple porencephalic periventricular cavities, cortical atrophy and subcortical leukomalacia (Fig. 2). Seizures were initially well controlled with
Neurological abnormalities are reported in 40-94% of the cases of HI. This wide range of incidence is related in part to different origins of the series from dermatologic or child neurology units [3]. Severity of neurological abnormalities does not correlate with either extent of cutaneous hypopigmented lesions or microscopic or radiological findings, but it seems to be associated with an early onset of symptoms [2]. The most frequent abnormality is mental retardation, present in more than 60% of the cases and commonly associated with early seizures [3]. There are several types of seizures described in these patients, most frequently infantile spasms or other types of myoclonic epilepsy [2,3]. EEG findings are not pathognomonic, although there is probably a group of patients with early and severe seizures, bizarre EEG abnormalities, poor prognosis and perhaps defects of neuronal migration [4]. Our patient's seizures could be due to his AVM and the lesions developed after surgery, but because they were infantile spasms with hypsarrhythmia, they point to a possible relationship with his HI. Numerous imaging (CT and MR) findings are described in HI including cerebral atrophy, hemimegalencephaly, diffuse hypodensity of white matter, porencephaly, periventricular cystic lesions, disorders of neuronal migration and agenesis of the corpus callosum, although imaging studies occasionally are normal [5,6]. Several chromosomal abnormalities have been described recently in HI karyotypes obtained mainly from cultured fibroblasts, most frequently mosaics for aneuploidy or unbalanced translocations of various chromosomes [7,8]. HI has already been associated with tumors outside the CNS (teratomas or epidermoid cysts of bone) [7] and intracranial tumors (choroid plexus papilloma) [8], but the finding of an intracerebral AVM has not previously been reported. The relationship between both alterations, HI and AVM, is difficult to assess. H1 and AVM are diseases that affect organs of different origin, ectoderm and mesoderm, respectively. The embryological period of maldevelopment is also different. Embryological migration of melanoblasts occurs in the second trimester [9], whereas the abnormal arteriovenous pattern characteristic of an AVM appears in the first trimester during the second stage of the development of cerebral blood vessels, arteries, capillaries and veins with intercommunications [10]. ACKNOWLEDGEMENTS The authors express their thanks to Dr. Harvey B. Sarnat (Seattle) for his help in preparing the manuscript.
REFERENCES
Fig. 2. MRT2 demonstrates ventriculomegaly, multiple porencephalic periventricular cavities, cortical atrophy and subcortical leukomalacia in the left cerebral hemisphere.
1. Hypomelanosis of Ito (Editorial). Lancet 1992; 339: 651-2. 2. Gordon N. Hypomelanosis of Ito (incontinentia pigmenti achromians). Dev Med Child Neurol 1994; 36: 271-4. 3. Pascual-Castroviejo I, L6pez-Rodrlguez 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.
80
E. Urgell~s et al./ Brain & Development 1996; 18:78-80
4. Esquivel EE, Pitt MC, Boyd SG. EEG findings in hypomelanosis of Ito. Neuropediatrics 1991; 22: 216-9. 5. Battistella PA, Peserico A, Bertoli P, Drigo P, Laverda AM, Casara GL. Hypomelanosis of Ito and hemimegalencephaly. Childs Nerv Syst 1990; 6: 421-3. 6. Williams DW, Elster AD. Cranial MR imaging in hypomelanosis of Ito. J Comput Assist Tomogr 1990; 14: 981-3. 7. Ishikawa T, Kanayama M, Sugiyama K, Katoh T, Wada Y. Hypomelanosis of lto associated with benign tumors and chromosomal abnormalities: a neurocutaneous syndrome. Brain Dev (Tokyo) 1985; 7: 45 -9.
8. Steichen-Gersdoff E, TrawSger R, Duba HC, Mayr U, Felber S, Utermann G. Hypomelanosis of Ito in a girl with plexus papilloma and translocation (X;17). Hum Genet 1993; 90: 611-3. 9. Ross DL, Liwnicz BH, Chun RWN, Gilbert E. Hypomelanosis of Ito (incontinentia pigmenti achromians). A clinicopathologic study; macrocephaly and gray matter heterotopias. Neurology 1982; 32: 1013-6. 10. Streeter GL. The developmental alterations in the vascular systems of the brain of the human embryo. Contrib Embryol Carnegie lnst 1918; 8: 5-8.