Brain & Development 37 (2015) 817–821 www.elsevier.com/locate/braindev
Case Report
Evolution of a symptomatic diffuse developmental venous anomaly with progressive cerebral atrophy in an atypical case of Sturge–Weber syndrome Koyo Ohno a,⇑, Yoshiaki Saito a, Masami Togawa a,b, Yuki Shinohara c, Takamichi Ito d, Hidenori Sugano e, Shinji Itamura a, Yoko Nishimura a, Akiko Tamasaki a, Yoshihiro Maegaki a a
Division of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan b Department of Paediatrics, Tottori Prefectural Central Hospital, Tottori, Japan c Division of Radiology, Department of Pathophysiological and Therapeutic Sciences, Faculty of Medicine, Tottori University, Yonago, Japan d Division of Dermatology, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, Tottori University, Yonago, Japan e Department of Neurosurgery, School of Medicine, Juntendo University, Tokyo, Japan Received 12 September 2014; received in revised form 2 December 2014; accepted 3 December 2014
Abstract A 2-year-old boy had glaucoma, bilateral facial haemangioma and widespread blue nevi on the trunk and extremities since birth. Dilated medullary veins were detected in the left cerebral periventricular white matter on magnetic resonance imaging (MRI). Macrocephaly and delayed psychomotor development were observed during late infancy, and susceptibility-weighted angiography revealed an extensive developmental venous anomaly with multiple caput medusae throughout bilateral hemispheres, accompanied by periventricular hyperintense alterations on MRI and progressive diffuse atrophy of the cerebral mantle with left-sided predominance. Hypoperfusion in the left cerebral and cerebellar hemisphere was also uncovered. No meningeal haemangioma was observed. This patient may represent a novel subgroup of phakomatosis cases that can be regarded as a variant of Sturge–Weber syndrome. Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Developmental venous anomaly; Phakomatosis; Sturge–Weber syndrome; Susceptibility-weighted imaging
1. Introduction Developmental venous anomalies (DVAs) are characterised by clustered dilatation of the superficial or deep venous system in the brain and are regarded as ⇑ Corresponding author at: Division of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan. Tel.: +81 859 38 6777; fax: +81 859 38 6779. E-mail address: [email protected] (K. Ohno).
anatomical variants of venous development. Dilated collecting veins are thought to perform the physiological function of normal venous drainage from the brain parenchyma, and DVAs are often present as incidental findings on neuroimaging. Individuals with DVAs are usually asymptomatic even if the anomaly spreads to the whole hemisphere [1–3], and only rarely do such patients present with headache and epilepsy or develop haemorrhage from accompanying anomalous vessels including cavernous malformations [4]. Venous stasis and outflow obstruction, possibly resulting from
http://dx.doi.org/10.1016/j.braindev.2014.12.003 0387-7604/Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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K. Ohno et al. / Brain & Development 37 (2015) 817–821
stenosis at the dural crossing or focal thickening of the collecting vein wall, can cause focal atrophy and hyperintense alterations of white matter on MRI of the brain parenchyma in the areas adjacent to the DVAs; however, the subjects remain asymptomatic even in the presence of these lesions [4,5]. We describe a case of a Japanese boy with extensive DVAs who has shown delayed psychomotor development since infancy, accompanied by progressive widespread atrophy of the cerebral cortex and white matter. He had congenital facial angioma and glaucoma that were suggestive of Sturge–Weber syndrome but showed no evidence of meningeal angioma. Nosological issues associated with this case are discussed at the end. 2. Case report We describe a case of a 2-year-old Japanese boy who was born to non-consanguineous parents after an uneventful pregnancy and was delivered at 37 weeks of gestation, with a birth weight of 2390 g [1.3 standard deviation (SD)], body length of 44.6 cm (1.4 SD) and head circumference of 33.7 cm (0.6 SD). Facial haemangioma and multiple blue nevi on the trunk and extremities were noted at birth. The baby presented with lagophthalmos. Trabeculotomy was performed for treating glaucoma 11 days after birth. Magnetic resonance imaging (MRI) on day 15 revealed dilated periventricular medullary veins in the anterior and posterior horns of the left lateral ventricle; other than that, the MRI findings were unremarkable (Fig. 1A and B). No signs of meningeal angioma were evident on gadolinium-enhanced MRI (data not shown). Psychomotor development was normal until the age of 7 months, when macrocephaly was first observed (Fig. 2A). Physical examination revealed that he had port-wine nevi bilaterally on the forehead and the right cheek and blue nevi representing dermal melanocytosis all over the extremities and the trunk (Fig. 2B and C). Neurological findings were unremarkable, and the developmental quotient of the patient was assessed as 98 on the Enjoji developmental scale (Tokyo, Japan, 1976). No epileptiform discharges were noted on electroencephalography. However, MRI uncovered progressive enlargement of the left lateral ventricles and hyperintense alterations in the periventricular white matter of the posterior horn (Fig. 1C and D). Susceptibilityweighted angiography (SWA) revealed clusters of dilated superficial veins (caput medusae) in the left sylvian, left posterior temporal, left medial occipital and right parietal areas (Fig. 1E and F). In the deep venous system, bilateral anterior septum veins were absent, and the right internal cerebral vein appeared to be hypoplastic. Subependymal veins in the right anterior and posterior horns were dilated (Fig. 1F). No signs of other types of vascular aberrations such as cavernous or
Fig. 1. Neuroimaging of developmental venous anomalies. (A)–(D) T2-weighted magnetic resonance imaging, (E) and (F) susceptibilityweighted angiography and (G) arterial spin labelling. (A) and (B) Day 15, (C)–(G) 1 year and 9 months of age. In A and B, radiating hypointense streaks are seen adjacent to the anterior and posterior horn of the left lateral ventricle. In C and D, progressive dilatation of lateral ventricles is present, in association with widening of the cortical sulcus and emergence of a hyperintense alteration in left posterior periventricular white matter. Dilated subependymal veins in the right anterior and posterior horns can be traced to the point where they join to form superficial veins in serial sections (data not shown). No hyperintense regions are observed in the dilated vasculature: this finding is suggestive of an arteriovenous shunt, which was identified in the susceptibility-weighted angiography images. Subdural fluid collection and haemorrhage are present in the right frontal area in C and D.
arteriovenous malformations were observed. Decreased perfusion was detected in the left hemisphere according to arterial spin labelling (ASL; Fig. 1G) along with attenuated blood flow in the left middle and posterior cerebral arteries on magnetic resonance angiography (data not shown).
K. Ohno et al. / Brain & Development 37 (2015) 817–821
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Fig. 2. (A) Development of the head circumference of the patient. Macrocephaly appeared at the age of 7 months and persisted. (B) and (C) Photographs of the patient at 2 years of age. Port-wine nevi on the bilateral forehead and right cheek (B) and blue nevi throughout the extremities and trunk (C) are noticeable. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Delayed psychomotor development of the patient became gradually apparent, developmental quotient being 83 at 14 months, 77 at 17 months and 71 at 24 months of age. He started to walk by age 17 months but still could not utter meaningful words at age 24 months. Muscle tone, deep tendon reflex and plantar responses were within the reference range. The patient had never experienced epileptic seizures. At 2 years of age, gadolinium-enhanced T1-weighted and fluid attenuated-inversion recovery (FLAIR) MRI did not show signs of meningeal angiomatosis. Computed-tomogra-
phy cisternography revealed normal drainage of contrast material from the ventricles. 3. Discussion Evolution of widespread DVAs with diffuse cerebral atrophy during infancy was unexpected given the initial MRI findings of focal dilation of medullary veins at the neonatal period. Susceptibility-weighted neuroimaging, the most effective method for non-invasive visualisation of venous malformations [2], revealed impairment of
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K. Ohno et al. / Brain & Development 37 (2015) 817–821
deep venous drainage because of the absent or hypoplastic vasculature joining the vein of Galen and the straight sinus since late infancy. Decreased cerebral blood flow in the left hemisphere is indicative of venous hypertension [6,7], probably resulting in further, more severe cerebral atrophy compared to the contralateral hemisphere. On the susceptibility-weighted angiography images, we could track the subependymal veins of the right lateral ventricles as they were draining through a transmantle anastomosis to the superficial system. Accordingly, the venous drainage was assumed to be less impaired in the right hemisphere despite more apparent defects in the internal cerebral vein and related venous structures on this side. Apart from very rare cases of progressive hemiparesis contralateral to the focal DVA in the centrum semiovale [8], our patient seems to represent the first reported case of global neurological symptoms accompanying progressive cerebral lesions from DVA. Neurosurgical intervention to relieve the venous hypertension (e.g., installation of shunts for drainage of the venous stasis) has not been reported; however, physicians should keep in mind that a DVA itself could be symptomatic in such rare cases. In the present case, the DVA seems to have evolved postnatally. Dilatation of collecting veins in the multiple caput medusae apparently became aggravated, and the drainage pathway was altered, with resultant cessation of blood flow in certain vessels. This report provides evidence that the pathogenesis of DVAs occurs in the prenatal period, and dilatation of veins propagates thereafter. These changes were not evident at birth in our patient, which suggests that the venous obstruction may start during a later foetal period in certain cases. Alternatively, there may be a shift of the route of venous drainage from the superficial to deep venous system at this stage because the venous system in the brain develops after arteries in the postnatal period [6]. Sturge–Weber syndrome is characterised by facial port-wine angioma, glaucoma and leptomeningeal angioma; a regression failure of the cephalic primitive embryonal vascular plexus has been hypothesised. A decrease of the blood flow in the cortical areas due to the pial angiomatosis results in focal hypoxia, causing progressive and paroxysmal neurological problems such as epilepsy, hemiparesis and cognitive regression. Gyriform hyperintensity in contrast-enhanced images, cortical calcification and brain atrophy are the typical findings on neuroimaging. Demonstration of meningeal angiomatosis is cardinal for the diagnosis of Sturge–Weber syndrome, which would prompt an appropriate management strategy including the surgical intervention for patients with progressive cerebral atrophy. In our patient, we could not find evidence of these cortical aberrations.
Contrast-enhanced FLAIR imaging is more sensitive than T1-weighted enhanced imaging in visualisation the leptomeningeal vascular lesions [9], however, no enhancement was observed in the present patient even with this technique. In contrast, SWA was most informative in the patient in demonstration of the anomalous venous structures, and is recommended in patients with progressive cerebral atrophy. SW imaging is also useful for evaluation of blood oxygenation [10]. Higher levels of the deoxyhaemoglobin due to decreased oxygenation might have contributed to a better visualisation of venous structures in the left hemisphere in the present patient. However, this assumption could not be quantitatively verified due to the limitation in the MR-unit in our hospital. Quantitative evaluation of blood oxygenation under appropriate protocols would be helpful for further understanding the pathophysiology of DVAs. The presence of blue nevi accompanying a port-wine stain in our patient is consistent with a dermatological diagnosis of phakomatosis pigmentovascularis (PPV) type IIb [11]. Some patients with this disease have comorbid DVAs or glaucoma, and distribution of portwine stains may involve either facial or non-facial areas [12,13]. That is, when patients with port-wine stains affect the facial areas, such patients have been reported to have the diagnosis of PPV accompanying Sturge– Weber syndrome. In the literature, meningeal angiomatosis in PPV with Sturge–Weber syndrome is either lacking [14] or atypical for Sturge–Weber syndrome [15]. Non-hydrocephalus macrocephaly, which is not usually observed in Sturge–Weber syndrome, is also common in PPV. Thus, we assume that our patient and these reported cases may represent a Sturge–Weber syndrome-like disorder characterised by macrocephaly, glaucoma, PPV and a DVA without evidence of pial angiomatosis. Because Sturge–Weber syndrome is a genetically heterogeneous entity [16], such characterisation of a small subgroup may be helpful for both management of the patients and genetic studies.
Acknowledgements We thank Mr. Eijiro Yamashita for his helpful comments regarding the evaluation of blood oxygenation by means of SWI. The authors declare that they have no interests that might be perceived as posing a conflict or bias. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/ 10.1016/j.braindev.2014.12.003.
K. Ohno et al. / Brain & Development 37 (2015) 817–821
References [1] Uchino A, Sawada A, Takase Y, Abe M, Kudo S. Cerebral hemiatrophy caused by multiple developmental venous anomalies involving nearly the entire cerebral hemisphere. Clin Imaging 2001;25:82–5. [2] Casey MA, Lahoti S, Gordhan A. Pediatric holohemispheric developmental venous anomaly: definitive characterization by 3D susceptibility weighted magnetic resonance angiography. J Radiol Case Rep 2011;5:10–8. [3] Jung AK, Henson JW, Susanto D, Caylor LM, Doherty MJ. Holohemispheric developmental venous anomaly. Neurology 2013;80:1718–9. [4] San Milla´n Ruı´z D, Delavelle J, Yilmaz H, Gailloud P, Piovan E, Bertramello A, et al. Parenchymal abnormalities associated with developmental venous anomalies. Neuroradiology 2007;49: 987–95. [5] Santucci GM, Leach JL, Ying J, Leach SD, Tomsick TA. Brain parenchymal signal abnormalities associated with developmental venous anomalies: detailed MR imaging assessment. AJNR Am J Neuroradiol 2008;29:1317–23. [6] Camacho DL, Smith JK, Grimme JD, Keyserling HF, Castillo M. Atypical MR imaging perfusion in developmental venous anomalies. AJNR Am J Neuroradiol 2004;25:1549–52. [7] Iv M, Fischbein NJ, Zaharchuk G. Association of developmental venous anomalies with perfusion abnormalities on arterial spin labeling and bolus perfusion-weighted imaging. J Neuroimaging 2014. http://dx.doi.org/10.1111/jon.12119. [8] Dillon WP. Cryptic vascular malformations: controversies in terminology, diagnosis, pathophysiology, and treatment. AJNR Am J Neuroradiol 1997;18:1839–46.
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[9] Griffiths PD, Coley SC, Romanowski CA, Hodgson T, Wilkinson ID. Contrast-enhanced fluid-attenuated inversion recovery imaging for leptomeningeal disease in children. ANJR Am J Neuroradiol 2003;24:719–23. [10] Fujima N, Kudo K, Terae S, Ishizaka K, Yazu R, Zaitsu Y, et al. Non-invasive measurement of oxygen saturation in the spinal vein using SWI: quantitative evaluation under conditions of physiological and caffeine load. Neuroimage 2011;54:344–9. [11] Happle R. Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 2005;141:385–8. [12] Finklea LB, Mohr MR, Warthan MM, Darrow DH, Williams JV. Two reports of phacomatosis pigmentovascularis type IIb, one in association with Sturge–Weber syndrome and Klippel–Trenaunay syndrome. Pediatr Dermatol 2010;27:303–5. [13] Toelle SP, Weibel L, Schiegl H, Boltshauser E. Phacomatosis pigmentovascularis and extensive venous malformation of brain vessels: an unknown association or a new vascular neurocutaneous syndrome? Neuropediatrics 2011;42:234–6. [14] Cho S, Choi JH, Sung KJ, Moon KC, Koh JK. Phakomatosis pigmentovascularis type IIB with neurologic abnormalities. Pediatr Dermatol 2001;18:263. [15] Chhajed M, Pandit S, Dhawan N, Jain A. Klippel–Trenaunay and Sturge–Weber overlap syndrome with phakomatosis pigmentovascularis. J Pediatr Neurosci 2010;5:138–40. [16] Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge–Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013;368:1971–9.
Case Report
Evolution of a symptomatic diffuse developmental venous anomaly with progressive cerebral atrophy in an atypical case of Sturge–Weber syndrome Koyo Ohno a,⇑, Yoshiaki Saito a, Masami Togawa a,b, Yuki Shinohara c, Takamichi Ito d, Hidenori Sugano e, Shinji Itamura a, Yoko Nishimura a, Akiko Tamasaki a, Yoshihiro Maegaki a a
Division of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan b Department of Paediatrics, Tottori Prefectural Central Hospital, Tottori, Japan c Division of Radiology, Department of Pathophysiological and Therapeutic Sciences, Faculty of Medicine, Tottori University, Yonago, Japan d Division of Dermatology, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, Tottori University, Yonago, Japan e Department of Neurosurgery, School of Medicine, Juntendo University, Tokyo, Japan Received 12 September 2014; received in revised form 2 December 2014; accepted 3 December 2014
Abstract A 2-year-old boy had glaucoma, bilateral facial haemangioma and widespread blue nevi on the trunk and extremities since birth. Dilated medullary veins were detected in the left cerebral periventricular white matter on magnetic resonance imaging (MRI). Macrocephaly and delayed psychomotor development were observed during late infancy, and susceptibility-weighted angiography revealed an extensive developmental venous anomaly with multiple caput medusae throughout bilateral hemispheres, accompanied by periventricular hyperintense alterations on MRI and progressive diffuse atrophy of the cerebral mantle with left-sided predominance. Hypoperfusion in the left cerebral and cerebellar hemisphere was also uncovered. No meningeal haemangioma was observed. This patient may represent a novel subgroup of phakomatosis cases that can be regarded as a variant of Sturge–Weber syndrome. Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Developmental venous anomaly; Phakomatosis; Sturge–Weber syndrome; Susceptibility-weighted imaging
1. Introduction Developmental venous anomalies (DVAs) are characterised by clustered dilatation of the superficial or deep venous system in the brain and are regarded as ⇑ Corresponding author at: Division of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan. Tel.: +81 859 38 6777; fax: +81 859 38 6779. E-mail address: [email protected] (K. Ohno).
anatomical variants of venous development. Dilated collecting veins are thought to perform the physiological function of normal venous drainage from the brain parenchyma, and DVAs are often present as incidental findings on neuroimaging. Individuals with DVAs are usually asymptomatic even if the anomaly spreads to the whole hemisphere [1–3], and only rarely do such patients present with headache and epilepsy or develop haemorrhage from accompanying anomalous vessels including cavernous malformations [4]. Venous stasis and outflow obstruction, possibly resulting from
http://dx.doi.org/10.1016/j.braindev.2014.12.003 0387-7604/Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
818
K. Ohno et al. / Brain & Development 37 (2015) 817–821
stenosis at the dural crossing or focal thickening of the collecting vein wall, can cause focal atrophy and hyperintense alterations of white matter on MRI of the brain parenchyma in the areas adjacent to the DVAs; however, the subjects remain asymptomatic even in the presence of these lesions [4,5]. We describe a case of a Japanese boy with extensive DVAs who has shown delayed psychomotor development since infancy, accompanied by progressive widespread atrophy of the cerebral cortex and white matter. He had congenital facial angioma and glaucoma that were suggestive of Sturge–Weber syndrome but showed no evidence of meningeal angioma. Nosological issues associated with this case are discussed at the end. 2. Case report We describe a case of a 2-year-old Japanese boy who was born to non-consanguineous parents after an uneventful pregnancy and was delivered at 37 weeks of gestation, with a birth weight of 2390 g [1.3 standard deviation (SD)], body length of 44.6 cm (1.4 SD) and head circumference of 33.7 cm (0.6 SD). Facial haemangioma and multiple blue nevi on the trunk and extremities were noted at birth. The baby presented with lagophthalmos. Trabeculotomy was performed for treating glaucoma 11 days after birth. Magnetic resonance imaging (MRI) on day 15 revealed dilated periventricular medullary veins in the anterior and posterior horns of the left lateral ventricle; other than that, the MRI findings were unremarkable (Fig. 1A and B). No signs of meningeal angioma were evident on gadolinium-enhanced MRI (data not shown). Psychomotor development was normal until the age of 7 months, when macrocephaly was first observed (Fig. 2A). Physical examination revealed that he had port-wine nevi bilaterally on the forehead and the right cheek and blue nevi representing dermal melanocytosis all over the extremities and the trunk (Fig. 2B and C). Neurological findings were unremarkable, and the developmental quotient of the patient was assessed as 98 on the Enjoji developmental scale (Tokyo, Japan, 1976). No epileptiform discharges were noted on electroencephalography. However, MRI uncovered progressive enlargement of the left lateral ventricles and hyperintense alterations in the periventricular white matter of the posterior horn (Fig. 1C and D). Susceptibilityweighted angiography (SWA) revealed clusters of dilated superficial veins (caput medusae) in the left sylvian, left posterior temporal, left medial occipital and right parietal areas (Fig. 1E and F). In the deep venous system, bilateral anterior septum veins were absent, and the right internal cerebral vein appeared to be hypoplastic. Subependymal veins in the right anterior and posterior horns were dilated (Fig. 1F). No signs of other types of vascular aberrations such as cavernous or
Fig. 1. Neuroimaging of developmental venous anomalies. (A)–(D) T2-weighted magnetic resonance imaging, (E) and (F) susceptibilityweighted angiography and (G) arterial spin labelling. (A) and (B) Day 15, (C)–(G) 1 year and 9 months of age. In A and B, radiating hypointense streaks are seen adjacent to the anterior and posterior horn of the left lateral ventricle. In C and D, progressive dilatation of lateral ventricles is present, in association with widening of the cortical sulcus and emergence of a hyperintense alteration in left posterior periventricular white matter. Dilated subependymal veins in the right anterior and posterior horns can be traced to the point where they join to form superficial veins in serial sections (data not shown). No hyperintense regions are observed in the dilated vasculature: this finding is suggestive of an arteriovenous shunt, which was identified in the susceptibility-weighted angiography images. Subdural fluid collection and haemorrhage are present in the right frontal area in C and D.
arteriovenous malformations were observed. Decreased perfusion was detected in the left hemisphere according to arterial spin labelling (ASL; Fig. 1G) along with attenuated blood flow in the left middle and posterior cerebral arteries on magnetic resonance angiography (data not shown).
K. Ohno et al. / Brain & Development 37 (2015) 817–821
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Fig. 2. (A) Development of the head circumference of the patient. Macrocephaly appeared at the age of 7 months and persisted. (B) and (C) Photographs of the patient at 2 years of age. Port-wine nevi on the bilateral forehead and right cheek (B) and blue nevi throughout the extremities and trunk (C) are noticeable. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Delayed psychomotor development of the patient became gradually apparent, developmental quotient being 83 at 14 months, 77 at 17 months and 71 at 24 months of age. He started to walk by age 17 months but still could not utter meaningful words at age 24 months. Muscle tone, deep tendon reflex and plantar responses were within the reference range. The patient had never experienced epileptic seizures. At 2 years of age, gadolinium-enhanced T1-weighted and fluid attenuated-inversion recovery (FLAIR) MRI did not show signs of meningeal angiomatosis. Computed-tomogra-
phy cisternography revealed normal drainage of contrast material from the ventricles. 3. Discussion Evolution of widespread DVAs with diffuse cerebral atrophy during infancy was unexpected given the initial MRI findings of focal dilation of medullary veins at the neonatal period. Susceptibility-weighted neuroimaging, the most effective method for non-invasive visualisation of venous malformations [2], revealed impairment of
820
K. Ohno et al. / Brain & Development 37 (2015) 817–821
deep venous drainage because of the absent or hypoplastic vasculature joining the vein of Galen and the straight sinus since late infancy. Decreased cerebral blood flow in the left hemisphere is indicative of venous hypertension [6,7], probably resulting in further, more severe cerebral atrophy compared to the contralateral hemisphere. On the susceptibility-weighted angiography images, we could track the subependymal veins of the right lateral ventricles as they were draining through a transmantle anastomosis to the superficial system. Accordingly, the venous drainage was assumed to be less impaired in the right hemisphere despite more apparent defects in the internal cerebral vein and related venous structures on this side. Apart from very rare cases of progressive hemiparesis contralateral to the focal DVA in the centrum semiovale [8], our patient seems to represent the first reported case of global neurological symptoms accompanying progressive cerebral lesions from DVA. Neurosurgical intervention to relieve the venous hypertension (e.g., installation of shunts for drainage of the venous stasis) has not been reported; however, physicians should keep in mind that a DVA itself could be symptomatic in such rare cases. In the present case, the DVA seems to have evolved postnatally. Dilatation of collecting veins in the multiple caput medusae apparently became aggravated, and the drainage pathway was altered, with resultant cessation of blood flow in certain vessels. This report provides evidence that the pathogenesis of DVAs occurs in the prenatal period, and dilatation of veins propagates thereafter. These changes were not evident at birth in our patient, which suggests that the venous obstruction may start during a later foetal period in certain cases. Alternatively, there may be a shift of the route of venous drainage from the superficial to deep venous system at this stage because the venous system in the brain develops after arteries in the postnatal period [6]. Sturge–Weber syndrome is characterised by facial port-wine angioma, glaucoma and leptomeningeal angioma; a regression failure of the cephalic primitive embryonal vascular plexus has been hypothesised. A decrease of the blood flow in the cortical areas due to the pial angiomatosis results in focal hypoxia, causing progressive and paroxysmal neurological problems such as epilepsy, hemiparesis and cognitive regression. Gyriform hyperintensity in contrast-enhanced images, cortical calcification and brain atrophy are the typical findings on neuroimaging. Demonstration of meningeal angiomatosis is cardinal for the diagnosis of Sturge–Weber syndrome, which would prompt an appropriate management strategy including the surgical intervention for patients with progressive cerebral atrophy. In our patient, we could not find evidence of these cortical aberrations.
Contrast-enhanced FLAIR imaging is more sensitive than T1-weighted enhanced imaging in visualisation the leptomeningeal vascular lesions [9], however, no enhancement was observed in the present patient even with this technique. In contrast, SWA was most informative in the patient in demonstration of the anomalous venous structures, and is recommended in patients with progressive cerebral atrophy. SW imaging is also useful for evaluation of blood oxygenation [10]. Higher levels of the deoxyhaemoglobin due to decreased oxygenation might have contributed to a better visualisation of venous structures in the left hemisphere in the present patient. However, this assumption could not be quantitatively verified due to the limitation in the MR-unit in our hospital. Quantitative evaluation of blood oxygenation under appropriate protocols would be helpful for further understanding the pathophysiology of DVAs. The presence of blue nevi accompanying a port-wine stain in our patient is consistent with a dermatological diagnosis of phakomatosis pigmentovascularis (PPV) type IIb [11]. Some patients with this disease have comorbid DVAs or glaucoma, and distribution of portwine stains may involve either facial or non-facial areas [12,13]. That is, when patients with port-wine stains affect the facial areas, such patients have been reported to have the diagnosis of PPV accompanying Sturge– Weber syndrome. In the literature, meningeal angiomatosis in PPV with Sturge–Weber syndrome is either lacking [14] or atypical for Sturge–Weber syndrome [15]. Non-hydrocephalus macrocephaly, which is not usually observed in Sturge–Weber syndrome, is also common in PPV. Thus, we assume that our patient and these reported cases may represent a Sturge–Weber syndrome-like disorder characterised by macrocephaly, glaucoma, PPV and a DVA without evidence of pial angiomatosis. Because Sturge–Weber syndrome is a genetically heterogeneous entity [16], such characterisation of a small subgroup may be helpful for both management of the patients and genetic studies.
Acknowledgements We thank Mr. Eijiro Yamashita for his helpful comments regarding the evaluation of blood oxygenation by means of SWI. The authors declare that they have no interests that might be perceived as posing a conflict or bias. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/ 10.1016/j.braindev.2014.12.003.
K. Ohno et al. / Brain & Development 37 (2015) 817–821
References [1] Uchino A, Sawada A, Takase Y, Abe M, Kudo S. Cerebral hemiatrophy caused by multiple developmental venous anomalies involving nearly the entire cerebral hemisphere. Clin Imaging 2001;25:82–5. [2] Casey MA, Lahoti S, Gordhan A. Pediatric holohemispheric developmental venous anomaly: definitive characterization by 3D susceptibility weighted magnetic resonance angiography. J Radiol Case Rep 2011;5:10–8. [3] Jung AK, Henson JW, Susanto D, Caylor LM, Doherty MJ. Holohemispheric developmental venous anomaly. Neurology 2013;80:1718–9. [4] San Milla´n Ruı´z D, Delavelle J, Yilmaz H, Gailloud P, Piovan E, Bertramello A, et al. Parenchymal abnormalities associated with developmental venous anomalies. Neuroradiology 2007;49: 987–95. [5] Santucci GM, Leach JL, Ying J, Leach SD, Tomsick TA. Brain parenchymal signal abnormalities associated with developmental venous anomalies: detailed MR imaging assessment. AJNR Am J Neuroradiol 2008;29:1317–23. [6] Camacho DL, Smith JK, Grimme JD, Keyserling HF, Castillo M. Atypical MR imaging perfusion in developmental venous anomalies. AJNR Am J Neuroradiol 2004;25:1549–52. [7] Iv M, Fischbein NJ, Zaharchuk G. Association of developmental venous anomalies with perfusion abnormalities on arterial spin labeling and bolus perfusion-weighted imaging. J Neuroimaging 2014. http://dx.doi.org/10.1111/jon.12119. [8] Dillon WP. Cryptic vascular malformations: controversies in terminology, diagnosis, pathophysiology, and treatment. AJNR Am J Neuroradiol 1997;18:1839–46.
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[9] Griffiths PD, Coley SC, Romanowski CA, Hodgson T, Wilkinson ID. Contrast-enhanced fluid-attenuated inversion recovery imaging for leptomeningeal disease in children. ANJR Am J Neuroradiol 2003;24:719–23. [10] Fujima N, Kudo K, Terae S, Ishizaka K, Yazu R, Zaitsu Y, et al. Non-invasive measurement of oxygen saturation in the spinal vein using SWI: quantitative evaluation under conditions of physiological and caffeine load. Neuroimage 2011;54:344–9. [11] Happle R. Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 2005;141:385–8. [12] Finklea LB, Mohr MR, Warthan MM, Darrow DH, Williams JV. Two reports of phacomatosis pigmentovascularis type IIb, one in association with Sturge–Weber syndrome and Klippel–Trenaunay syndrome. Pediatr Dermatol 2010;27:303–5. [13] Toelle SP, Weibel L, Schiegl H, Boltshauser E. Phacomatosis pigmentovascularis and extensive venous malformation of brain vessels: an unknown association or a new vascular neurocutaneous syndrome? Neuropediatrics 2011;42:234–6. [14] Cho S, Choi JH, Sung KJ, Moon KC, Koh JK. Phakomatosis pigmentovascularis type IIB with neurologic abnormalities. Pediatr Dermatol 2001;18:263. [15] Chhajed M, Pandit S, Dhawan N, Jain A. Klippel–Trenaunay and Sturge–Weber overlap syndrome with phakomatosis pigmentovascularis. J Pediatr Neurosci 2010;5:138–40. [16] Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge–Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013;368:1971–9.
