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Leptomeningeal angiomatosis with infantile spasms
Case Reports
Leptomeningeal Angiomatosis With Infantile Spasms Sahoko Miyama, MD and Tomohide Goto, MD
sometimes considered as a variant of Sturge-Weber syndrome. This report describes a patient with leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Her clinical manifestations are compared with those of Sturge-Weber syndrome and other reported cases of leptomeningeal angiomatosis without facial nevus, and the embryologic origin of this type of congenital angiomatosis is discussed. Case Report
We describe a 7-month-old female with leptomeningeal angiomatosis who developed infantile spasms. She did not manifest facial nevus or ocular choroidal angioma. Leptomeningeal angiomatosis is characterized by venous angiomas of leptomeninges and usually accompanied by facial nevus, a condition known as SturgeWeber syndrome. In Sturge-Weber syndrome, leptomeningeal angiomas can cause infantile spasms but much less frequently than in other neurocutaneous syndromes, such as tuberous sclerosis. This patient is the first reported case of leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Leptomeningeal angiomas should be taken into consideration as a cause of infantile spasms, even in the absence of facial nevus. We suggest that this case is clinically within the spectrum of Sturge-Weber syndrome, and that the embryologic origin of this case is similar to that of Sturge-Weber syndrome. © 2004 by Elsevier Inc. All rights reserved. Miyama S, Goto T. Leptomeningeal angiomatosis with infantile spasms. Pediatr Neurol 2004;31:353-356.
Introduction Leptomeningeal angiomatosis is a congenital vascular anomaly characterized by venous angiomas of leptomeninges. In most cases, it is accompanied by facial portwine nevus, known as Sturge-Weber syndrome. A few patients with leptomeningeal angiomatosis without facial involvement have been previously described [1-5], and
From the Department of Neurology, Tokyo Metropolitan Kiyose Children’s Hospital, Tokyo, Japan.
© 2004 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2004.05.010 ● 0887-8994/04/$—see front matter
A 7-month-old female was admitted to Tokyo Metropolitan Kiyose Children’s Hospital because of episodes of loss of consciousness. She was born after an uncomplicated pregnancy and uneventful delivery. Her motor and mental developments were normal, with no past history of febrile seizures or serious head trauma. There was no family history of febrile seizures or epilepsy. At 7 months, she developed several episodes of loss of consciousness for up to 10 minutes, with her head turned and eyes deviated to right. Physical examination was normal. She did not have facial port-wine stain or hypopigmented spots. Glaucoma or buphthalmos did not exist. Cranial computed tomography revealed slight atrophy of the left cerebral hemisphere without apparent calcification (Fig 1). Electroencephalography documented no epileptiform discharges or asymmetry of the background activity. Carbamazepine satisfactorily controlled her seizures. At 12 months, she developed series of seizures with sudden flexion of the head, trunk, arms, and legs. The series lasted for approximately 10 minutes, 4 to 5 times daily. Electroencephalogram indicated modified hypsarrhythmia (Fig 2). She was diagnosed as having infantile spasms. Valproate was administered, which was partially effective. After the addition of clonazepam, the seizures were controlled completely and the hypsarrhythmia observed on electroencephalography disappeared. During the several months after the onset of infantile spasms, delay in her language development gradually became evident. Cranial computed tomography at 17 months revealed cortical and subcortical calcifications in the left occipital lobe (Fig 3A). Further atrophy of the left cerebral hemisphere was apparent, especially in the occipital and parietal lobes. Magnetic resonance imaging revealed enhancement of the subarachnoid space along with the gyri and cortical sulci over the left occipital, parietal, and temporal lobes, indicating leptomeningeal angiomatosis (Fig 3B). Even at this point, no hemiparesis was observed. Electroencephalogram at 19 months revealed slowing of the background activity in the left parietal region, which was related to the distribution of the leptomeningeal angioma recognized on magnetic resonance imaging.
Discussion Leptomeningeal angiomatosis is characterized by vascular malformation of leptomeninges. Thickened and hy-
Communications should be addressed to: Dr. Miyama; Department of Neurology; Tokyo Metropolitan Kiyose Children’s Hospital; 1-3-1 Umezono; Kiyose-shi; Tokyo 204-8567, Japan. Received February 12, 2004; accepted May 21, 2004.
Miyama and Goto: Leptomeningeal Angiomatosis 353
Figure 1. Cranial computed tomography at 7 months when the patient developed initial seizures. Only slight atrophy of the left cerebral hemisphere was observed. No calcification was detected.
pervascularized leptomeninges are demonstrated on neuropathologic studies. Leptomeningeal angiomatosis is one of the features of Sturge-Weber syndrome, which is also known as encephalofacial angiomatosis. In Sturge-Weber syndrome, leptomeningeal angiomas usually exist over the unilateral parietal, temporal, or occipital lobes, although the frontal lobes or bilateral hemispheres are occasionally affected. Progressive calcifications and atrophy occur in the cerebral cortex underlying the leptomeningeal angioma. Facial angiomas most often involve the territory of the ophthalmic branch of the trigeminal nerve, including the forehead and the upper eyelid. Ocular choroidal angiomas are sometimes observed. Patients usually have seizures, hemiparesis, and mental retardation. This patient had a leptomeningeal angioma without facial nevus or ocular vascular anomaly. In a neuroimaging study, the distribution of the leptomeningeal angioma was similar to that in Sturge-Weber syndrome, i.e., over the unilateral parietal, occipital, and temporal lobes. Calcifications and progressive atrophy of the affected cerebral hemisphere were evident. These neuroimaging manifestations agree with those observed in Sturge-Weber syndrome. There have been several reports of cases with leptomeningeal angiomatosis without facial nevus so far. Some of these patients had leptomeningeal angiomas in the typical regions of Sturge-Weber syndrome [1], but in others the leptomeningeal angiomas existed in the frontal region [2,3] or bilateral occipital calcifications were
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present [4,5]. Although there is controversy concerning whether or not these patients with leptomeningeal angiomatosis without facial nevus should be included in SturgeWeber syndrome, we consider that our patient is within the spectrum of Sturge-Weber syndrome because of the typical features of the neuroimages. The patient had complex partial seizures initially and developed infantile spasms later. In Sturge-Weber syndrome, leptomeningeal angiomas often cause intractable seizures, such as partial motor seizures, generalized tonic-clonic seizures [6], and much less frequently, infantile spasms [7]. Our patient is the first reported case of leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Leptomeningeal angiomas have to be taken into consideration as a cause of infantile spasms, even in the absence of facial nevus. The electroencephalographic findings changed considerably during the 12 months after the initial epileptic episodes. Neurologic abnormalities in Sturge-Weber syndrome are the result of the hypoxic injury caused by the venous congestion in the affected cerebral cortex [6]. It is suggested that acute progression of cerebral parenchymal dysfunction caused the changes in seizure manifestations and electroencephalographic findings after the onset of epilepsy in our patient. Cranial computed tomography at the onset of the epileptic seizures revealed only slight atrophy of the affected cerebral hemisphere. No calcification in the cerebral cortex was observed. We did not think of leptomeningeal angiomatosis at the time because of the absence of calcification on cranial computed tomography or facial nevus. Clinically, leptomeningeal angiomatosis may not even be considered if calcification is absent on cranial computed tomography at the early stage of the disease, especially when the patient manifests no facial angioma. We suggest that contrast-enhanced computed tomography or magnetic resonance imaging should be performed for pediatric patients with epilepsy when atrophy of the unilateral cerebral hemisphere exists. In Sturge-Weber syndrome, the mechanism of the simultaneous occurrence of facial and leptomeningeal angiomas is not well known. Using quail-chick chimeras, Couly and Le Douarin observed that both of the telencephalic meninges and the mesectoderm of the upper facial region originated from the mesencephalic (and partially the prosencephalic) neural crest [8]. Notably, in the telencephalic meninges, the blood vessel walls, including the pericytes and the musculoconnective elements, were derived from the neural crest cells. A somatic mutation, which occurs in one of the early precursors of the prosencephalic and mesencephalic neural crest cells, could be a cause of the simultaneous occurrence of meningeal and upper facial angiomas [8]. If such a somatic mutation occurs later, i.e., after these precursors have differentiated into meningeal precursors and mesectodermal precursors of the upper facial region, then an angioma can appear either in the meninges or in the upper facial region. This hypothesis not only accounts for the embryologic origin of
Figure 2. Electroencephalogram when the patient developed infantile spasms. Spike-wave complexes appear over the left parietal and right occipital regions, and synchrony of the paroxysms between both cerebral hemispheres is observed, indicating modified hypsarrhythmia.
a leptomeningeal angioma without facial nevus, but also accounts for that of an upper facial angioma without a leptomeningeal angioma, which is proposed to be another
subtype of Sturge-Weber syndrome [9,10]. Further advances in embryology will clarify the origin of variants of Sturge-Weber syndrome.
Figure 3. (A) Cranial computed tomography at 17 months revealed cortical and subcortical calcifications in the left occipital lobe and progressive atrophy of the left cerebral hemisphere. (B) Contrast-enhanced magnetic resonance imaging (TR: 360 ms, TE: 9 ms) revealed left leptomeningeal angioma over the occipital, parietal, and temporal lobes.
Miyama and Goto: Leptomeningeal Angiomatosis 355
References [1] Aydin A, Cakmakci H, Kovanlikaya A, Dirik E. Sturge-Weber syndrome without facial nevus. Pediatr Neurol 2000;22:400-2. [2] Dilber C, Tasdemir HA, Dagdemir A, Incesu L, Odaci E. Sturge-Weber syndrome involved frontoparietal region without facial nevus. Pediatr Neurol 2002;26:387-90. [3] Comi AM, Fischer R, Kossoff EH. Encephalofacial angiomatosis sparing the occipital lobe and without facial nevus: On the spectrum of Sturge-Weber syndrome variants? J Child Neurol 2003; 18:35-8. [4] Taly B, Nagaraja D, Das S, Shankar SK, Pratibha NG. SturgeWeber-Dimitri disease without facial nevus. Neurology 1987;37:1063-4. [5] Gobbi G, Sorrenti G, Santucci M, et al. Epilepsy with bilateral
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occipital calcifications: A benign onset with progressive severity. Neurology 1988;38:913-20. [6] Berg BO. Neurocutaneous syndromes. In: Swaiman KF, Ashwal S, eds. Pediatric neurology, 3rd ed. St. Louis: Mosby, 1999:530-49. [7] Fukuyama S, Tsuchiya S. A study on Sturge-Weber syndrome: Report of a case associated with infantile spasms and electroencephalographic evolution in five cases. Eur Neurol 1979;18:194-204. [8] Couly GF, Le Douarin NM. Mapping of the early neural primordium in quail-chick chimeras. Dev Biol 1987;120:198-214. [9] Roach ES. Neurocutaneous syndrome. Pediatr Clin North Am 1992;39:591-620. [10] Enjolras O, Riche MC, Merland JJ. Facial port-wine stains and Sturge-Weber syndrome. Pediatrics 1985;76:48-51.
Leptomeningeal Angiomatosis With Infantile Spasms Sahoko Miyama, MD and Tomohide Goto, MD
sometimes considered as a variant of Sturge-Weber syndrome. This report describes a patient with leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Her clinical manifestations are compared with those of Sturge-Weber syndrome and other reported cases of leptomeningeal angiomatosis without facial nevus, and the embryologic origin of this type of congenital angiomatosis is discussed. Case Report
We describe a 7-month-old female with leptomeningeal angiomatosis who developed infantile spasms. She did not manifest facial nevus or ocular choroidal angioma. Leptomeningeal angiomatosis is characterized by venous angiomas of leptomeninges and usually accompanied by facial nevus, a condition known as SturgeWeber syndrome. In Sturge-Weber syndrome, leptomeningeal angiomas can cause infantile spasms but much less frequently than in other neurocutaneous syndromes, such as tuberous sclerosis. This patient is the first reported case of leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Leptomeningeal angiomas should be taken into consideration as a cause of infantile spasms, even in the absence of facial nevus. We suggest that this case is clinically within the spectrum of Sturge-Weber syndrome, and that the embryologic origin of this case is similar to that of Sturge-Weber syndrome. © 2004 by Elsevier Inc. All rights reserved. Miyama S, Goto T. Leptomeningeal angiomatosis with infantile spasms. Pediatr Neurol 2004;31:353-356.
Introduction Leptomeningeal angiomatosis is a congenital vascular anomaly characterized by venous angiomas of leptomeninges. In most cases, it is accompanied by facial portwine nevus, known as Sturge-Weber syndrome. A few patients with leptomeningeal angiomatosis without facial involvement have been previously described [1-5], and
From the Department of Neurology, Tokyo Metropolitan Kiyose Children’s Hospital, Tokyo, Japan.
© 2004 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2004.05.010 ● 0887-8994/04/$—see front matter
A 7-month-old female was admitted to Tokyo Metropolitan Kiyose Children’s Hospital because of episodes of loss of consciousness. She was born after an uncomplicated pregnancy and uneventful delivery. Her motor and mental developments were normal, with no past history of febrile seizures or serious head trauma. There was no family history of febrile seizures or epilepsy. At 7 months, she developed several episodes of loss of consciousness for up to 10 minutes, with her head turned and eyes deviated to right. Physical examination was normal. She did not have facial port-wine stain or hypopigmented spots. Glaucoma or buphthalmos did not exist. Cranial computed tomography revealed slight atrophy of the left cerebral hemisphere without apparent calcification (Fig 1). Electroencephalography documented no epileptiform discharges or asymmetry of the background activity. Carbamazepine satisfactorily controlled her seizures. At 12 months, she developed series of seizures with sudden flexion of the head, trunk, arms, and legs. The series lasted for approximately 10 minutes, 4 to 5 times daily. Electroencephalogram indicated modified hypsarrhythmia (Fig 2). She was diagnosed as having infantile spasms. Valproate was administered, which was partially effective. After the addition of clonazepam, the seizures were controlled completely and the hypsarrhythmia observed on electroencephalography disappeared. During the several months after the onset of infantile spasms, delay in her language development gradually became evident. Cranial computed tomography at 17 months revealed cortical and subcortical calcifications in the left occipital lobe (Fig 3A). Further atrophy of the left cerebral hemisphere was apparent, especially in the occipital and parietal lobes. Magnetic resonance imaging revealed enhancement of the subarachnoid space along with the gyri and cortical sulci over the left occipital, parietal, and temporal lobes, indicating leptomeningeal angiomatosis (Fig 3B). Even at this point, no hemiparesis was observed. Electroencephalogram at 19 months revealed slowing of the background activity in the left parietal region, which was related to the distribution of the leptomeningeal angioma recognized on magnetic resonance imaging.
Discussion Leptomeningeal angiomatosis is characterized by vascular malformation of leptomeninges. Thickened and hy-
Communications should be addressed to: Dr. Miyama; Department of Neurology; Tokyo Metropolitan Kiyose Children’s Hospital; 1-3-1 Umezono; Kiyose-shi; Tokyo 204-8567, Japan. Received February 12, 2004; accepted May 21, 2004.
Miyama and Goto: Leptomeningeal Angiomatosis 353
Figure 1. Cranial computed tomography at 7 months when the patient developed initial seizures. Only slight atrophy of the left cerebral hemisphere was observed. No calcification was detected.
pervascularized leptomeninges are demonstrated on neuropathologic studies. Leptomeningeal angiomatosis is one of the features of Sturge-Weber syndrome, which is also known as encephalofacial angiomatosis. In Sturge-Weber syndrome, leptomeningeal angiomas usually exist over the unilateral parietal, temporal, or occipital lobes, although the frontal lobes or bilateral hemispheres are occasionally affected. Progressive calcifications and atrophy occur in the cerebral cortex underlying the leptomeningeal angioma. Facial angiomas most often involve the territory of the ophthalmic branch of the trigeminal nerve, including the forehead and the upper eyelid. Ocular choroidal angiomas are sometimes observed. Patients usually have seizures, hemiparesis, and mental retardation. This patient had a leptomeningeal angioma without facial nevus or ocular vascular anomaly. In a neuroimaging study, the distribution of the leptomeningeal angioma was similar to that in Sturge-Weber syndrome, i.e., over the unilateral parietal, occipital, and temporal lobes. Calcifications and progressive atrophy of the affected cerebral hemisphere were evident. These neuroimaging manifestations agree with those observed in Sturge-Weber syndrome. There have been several reports of cases with leptomeningeal angiomatosis without facial nevus so far. Some of these patients had leptomeningeal angiomas in the typical regions of Sturge-Weber syndrome [1], but in others the leptomeningeal angiomas existed in the frontal region [2,3] or bilateral occipital calcifications were
354
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Vol. 31 No. 5
present [4,5]. Although there is controversy concerning whether or not these patients with leptomeningeal angiomatosis without facial nevus should be included in SturgeWeber syndrome, we consider that our patient is within the spectrum of Sturge-Weber syndrome because of the typical features of the neuroimages. The patient had complex partial seizures initially and developed infantile spasms later. In Sturge-Weber syndrome, leptomeningeal angiomas often cause intractable seizures, such as partial motor seizures, generalized tonic-clonic seizures [6], and much less frequently, infantile spasms [7]. Our patient is the first reported case of leptomeningeal angiomatosis without facial nevus who developed infantile spasms. Leptomeningeal angiomas have to be taken into consideration as a cause of infantile spasms, even in the absence of facial nevus. The electroencephalographic findings changed considerably during the 12 months after the initial epileptic episodes. Neurologic abnormalities in Sturge-Weber syndrome are the result of the hypoxic injury caused by the venous congestion in the affected cerebral cortex [6]. It is suggested that acute progression of cerebral parenchymal dysfunction caused the changes in seizure manifestations and electroencephalographic findings after the onset of epilepsy in our patient. Cranial computed tomography at the onset of the epileptic seizures revealed only slight atrophy of the affected cerebral hemisphere. No calcification in the cerebral cortex was observed. We did not think of leptomeningeal angiomatosis at the time because of the absence of calcification on cranial computed tomography or facial nevus. Clinically, leptomeningeal angiomatosis may not even be considered if calcification is absent on cranial computed tomography at the early stage of the disease, especially when the patient manifests no facial angioma. We suggest that contrast-enhanced computed tomography or magnetic resonance imaging should be performed for pediatric patients with epilepsy when atrophy of the unilateral cerebral hemisphere exists. In Sturge-Weber syndrome, the mechanism of the simultaneous occurrence of facial and leptomeningeal angiomas is not well known. Using quail-chick chimeras, Couly and Le Douarin observed that both of the telencephalic meninges and the mesectoderm of the upper facial region originated from the mesencephalic (and partially the prosencephalic) neural crest [8]. Notably, in the telencephalic meninges, the blood vessel walls, including the pericytes and the musculoconnective elements, were derived from the neural crest cells. A somatic mutation, which occurs in one of the early precursors of the prosencephalic and mesencephalic neural crest cells, could be a cause of the simultaneous occurrence of meningeal and upper facial angiomas [8]. If such a somatic mutation occurs later, i.e., after these precursors have differentiated into meningeal precursors and mesectodermal precursors of the upper facial region, then an angioma can appear either in the meninges or in the upper facial region. This hypothesis not only accounts for the embryologic origin of
Figure 2. Electroencephalogram when the patient developed infantile spasms. Spike-wave complexes appear over the left parietal and right occipital regions, and synchrony of the paroxysms between both cerebral hemispheres is observed, indicating modified hypsarrhythmia.
a leptomeningeal angioma without facial nevus, but also accounts for that of an upper facial angioma without a leptomeningeal angioma, which is proposed to be another
subtype of Sturge-Weber syndrome [9,10]. Further advances in embryology will clarify the origin of variants of Sturge-Weber syndrome.
Figure 3. (A) Cranial computed tomography at 17 months revealed cortical and subcortical calcifications in the left occipital lobe and progressive atrophy of the left cerebral hemisphere. (B) Contrast-enhanced magnetic resonance imaging (TR: 360 ms, TE: 9 ms) revealed left leptomeningeal angioma over the occipital, parietal, and temporal lobes.
Miyama and Goto: Leptomeningeal Angiomatosis 355
References [1] Aydin A, Cakmakci H, Kovanlikaya A, Dirik E. Sturge-Weber syndrome without facial nevus. Pediatr Neurol 2000;22:400-2. [2] Dilber C, Tasdemir HA, Dagdemir A, Incesu L, Odaci E. Sturge-Weber syndrome involved frontoparietal region without facial nevus. Pediatr Neurol 2002;26:387-90. [3] Comi AM, Fischer R, Kossoff EH. Encephalofacial angiomatosis sparing the occipital lobe and without facial nevus: On the spectrum of Sturge-Weber syndrome variants? J Child Neurol 2003; 18:35-8. [4] Taly B, Nagaraja D, Das S, Shankar SK, Pratibha NG. SturgeWeber-Dimitri disease without facial nevus. Neurology 1987;37:1063-4. [5] Gobbi G, Sorrenti G, Santucci M, et al. Epilepsy with bilateral
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occipital calcifications: A benign onset with progressive severity. Neurology 1988;38:913-20. [6] Berg BO. Neurocutaneous syndromes. In: Swaiman KF, Ashwal S, eds. Pediatric neurology, 3rd ed. St. Louis: Mosby, 1999:530-49. [7] Fukuyama S, Tsuchiya S. A study on Sturge-Weber syndrome: Report of a case associated with infantile spasms and electroencephalographic evolution in five cases. Eur Neurol 1979;18:194-204. [8] Couly GF, Le Douarin NM. Mapping of the early neural primordium in quail-chick chimeras. Dev Biol 1987;120:198-214. [9] Roach ES. Neurocutaneous syndrome. Pediatr Clin North Am 1992;39:591-620. [10] Enjolras O, Riche MC, Merland JJ. Facial port-wine stains and Sturge-Weber syndrome. Pediatrics 1985;76:48-51.