NEUROLOGICAL RARITIES
Rarities in neurology: blue rubber bleb naevus syndrome Ray Wynford-Thomas,1 Ann Johnston,1 Shawn Halpin,2 Khalid Hamandi1,3
1
Department of Neurology, University Hospital of Wales, Cardiff, UK 2 Department of Neuroradiology, University Hospital of Wales, Cardiff, UK 3 Alan Richens Welsh Epilepsy Unit, University Hospital of Wales, Cardiff, UK Correspondence to Dr Ray Wynford-Thomas, Department of Neurology, University Hospital of Wales, Cardiff, Heath Park CF14 4XW, UK; [email protected]
To cite: Wynford-Thomas R, Johnston A, Halpin S, et al. Pract Neurol Published Online First: [ please include Day Month Year] doi:10.1136/ practneurol-2013-000725
ABSTRACT A 62-year-old woman presented with stabbing pain over her left temple radiating to her left cheek when bending forwards or coughing. Neurological examination was normal. There were many cutaneous venous prominences over her body. CT and MR brain scans showed multiple venous anomalies and venous occlusive disease of the left sylvian fissure and superior sagittal sinus. We excluded arteriovenous malformation and dural fistulae with cerebral angiography. Following a clinical genetics assessment, we diagnosed blue rubber bleb naevus syndrome (BRBNS) and gave amitriptyline for her pain. There are only 200 cases of BRBNS in the literature, and central nervous system involvement is rarer still. The syndrome involves multiple cutaneous and visceral venous malformations. Most appear to be sporadic though a few have autosomal dominant inheritance. Although rare, BRBNS represents an important differential diagnosis for patients presenting with multiple and/or multisystem vascular malformations.
INTRODUCTION A 62-year-old woman gave a 7-month history of stabbing pain over her left temple radiating to her left cheek, exclusively on bending forwards and on coughing. She took no medication and did not drink alcohol or smoke. One sibling had primary lateral sclerosis and another had Addison’s disease. Examination of her skin and mucous membranes showed multiple cutaneous venous prominences, predominantly on her chest (figure 1B,C) and in her mouth (figure 1D). There were also many other similar lesions scattered over her body. These bleb-like lesions were dark blue and compressible, re-filling with release. A lesion around the inner border of the left eyelid became more prominent on bending forwards or coughing. A full neurological and systems examination
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
was normal, with no focal motor or sensory deficit involving the left trigeminal nerve. The venous prominences in her mouth had been present since birth, and further oral lesions had appeared in her fourth decade. With time, similar bleb-like lesions appeared all over her body and increased in size. More recently, she had developed lesions on her right hand (figure 1A), on her lip (figure 1B), beneath her tongue (figure 1D) and on her right eyelid. A biopsy suggested a vascular malformation, such as a hamartoma with superadded thrombosis. A CT scan of head and MR brain imaging with angiography showed multiple venous anomalies (figures 2A–D) and venous occlusive disease of the left sylvian fissure and superior sagittal sinus (figure 3). We excluded arteriovenous malformations and dural fistulae with cerebral angiography (figures 2B,C). Following a clinical genetics assessment, we diagnosed blue rubber bleb naevus syndrome. Her symptoms have responded well to low-dose amitriptyline. DISCUSSION Blue rubber bleb naevus syndrome (BRBNS) is rare. It is characterised by multiple cutaneous and visceral venous malformations. First described in 1860, there are only around 200 case reports in the literature.1 Although most appear to be sporadic, some have autosomal-dominant inheritance with linkage to chromosome 9p. The underlying mechanism is not yet known, but tyrosine kinase probably plays a role in venous malformations. The presentation of BRBNS differs with the site of the lesions. ▸ Cutaneous lesions characteristically are dark blue, compressible, rubbery blebs of varying size. They are typically formed by
1
NEUROLOGICAL RARITIES
Figure 1 (A) Venous prominences on right hand, circled in red. (B) Venous prominences on chest, circled in red. (C) Close-up of venous prominences on chest. (D) Venous prominences in oral cavity.
Figure 2 (A–C) Sagittal MRI angiography images illustrating a venous anomaly running down from the sagittal sinus (red arrow). (D) MRI axial T2 image illustrating a venous anomaly adjacent to trigeminal nerve root (red arrow).
2
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
NEUROLOGICAL RARITIES
Figure 3 MRI axial FLAIR image illustrating a left-sided cavernous haemangioma (top red arrow) and aberrant tissue in the expected position of the superior sagittal sinus (bottom red arrow).
a single layer of endothelial cells lining a cavernous space and are separated by fibrous and collagenous tissue. Being of embryonic origin, the venous malformations are present at birth. However, patients may not notice lesions until later in life, as they increase in size and frequency. They may occur anywhere on the body, but are most common on the trunk, limbs and face. They do not appear to bleed spontaneously, but sometimes cause pain or hyperhidrosis. ▸ Extracutaneous lesions include involvement of the gastrointestinal system, bone, heart, lungs, kidneys and the central nervous system (CNS). Their variable location explains a multitude of presentations: the diagnosis of BRBNS may easily be missed. For example, iron deficiency anaemia may result from occult gastrointestinal bleeding. BRBNS also has the potential to cause fatal bleeding; hence its early recognition is important. CNS-associated BRBNS can cause spinal cord compression from multiple extradural venous malformations, right abducens nerve palsy, a dural arteriovenous fistula, epilepsy, progressive ataxia and brainstem signs.
The lesions do not undergo neoplastic change. Treatment is either conservative or more invasive with endoscopy, surgery, steroid laser therapy and sirolimus. Trigeminal neuralgia is usually caused by trigeminal nerve root compression by an aberrant arterial loop, resulting in focal demyelination of the afferent trigeminal nerve fibres and close apposition of demyelinated axons. Venous loops may also be implicated. This local effect on the nerve is thought to result in the spontaneous production of impulses, as well as ephaptic conduction.2 In this patient, the hemifacial pain probably resulted from transient compression of the trigeminal root entry zone, occurring only when there is increased intracranial venous filling during Valsalva or postural change. This differs in character from typical trigeminal neuralgia (ie, not lancinating and brief ) in that the substrate is venous rather than arterial. CONCLUSION BRBNS is a rare vascular disorder with CNS involvement. A neurological examination should include a search for cutaneous lesions and these considered in the differential diagnosis. Our case also highlights an interesting association between transient trigeminal root compression or irritation and hemifacial pain. Acknowledgements The authors are grateful to the patient for permission to publish this case report. Contributors RW-T is the lead author and main contributor. The other authors have all equally contributed to the manuscript and have read and approved it. Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Mark Manford, Cambridge, UK.
REFERENCES
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
1 Nahm WK, Moise S, Eichenfield LF, et al. Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. J Am Acad Dermatol 2004;50:101–6. 2 Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis. Brain 2001;124:2347–60.
3
Rarities in neurology: blue rubber bleb naevus syndrome Ray Wynford-Thomas,1 Ann Johnston,1 Shawn Halpin,2 Khalid Hamandi1,3
1
Department of Neurology, University Hospital of Wales, Cardiff, UK 2 Department of Neuroradiology, University Hospital of Wales, Cardiff, UK 3 Alan Richens Welsh Epilepsy Unit, University Hospital of Wales, Cardiff, UK Correspondence to Dr Ray Wynford-Thomas, Department of Neurology, University Hospital of Wales, Cardiff, Heath Park CF14 4XW, UK; [email protected]
To cite: Wynford-Thomas R, Johnston A, Halpin S, et al. Pract Neurol Published Online First: [ please include Day Month Year] doi:10.1136/ practneurol-2013-000725
ABSTRACT A 62-year-old woman presented with stabbing pain over her left temple radiating to her left cheek when bending forwards or coughing. Neurological examination was normal. There were many cutaneous venous prominences over her body. CT and MR brain scans showed multiple venous anomalies and venous occlusive disease of the left sylvian fissure and superior sagittal sinus. We excluded arteriovenous malformation and dural fistulae with cerebral angiography. Following a clinical genetics assessment, we diagnosed blue rubber bleb naevus syndrome (BRBNS) and gave amitriptyline for her pain. There are only 200 cases of BRBNS in the literature, and central nervous system involvement is rarer still. The syndrome involves multiple cutaneous and visceral venous malformations. Most appear to be sporadic though a few have autosomal dominant inheritance. Although rare, BRBNS represents an important differential diagnosis for patients presenting with multiple and/or multisystem vascular malformations.
INTRODUCTION A 62-year-old woman gave a 7-month history of stabbing pain over her left temple radiating to her left cheek, exclusively on bending forwards and on coughing. She took no medication and did not drink alcohol or smoke. One sibling had primary lateral sclerosis and another had Addison’s disease. Examination of her skin and mucous membranes showed multiple cutaneous venous prominences, predominantly on her chest (figure 1B,C) and in her mouth (figure 1D). There were also many other similar lesions scattered over her body. These bleb-like lesions were dark blue and compressible, re-filling with release. A lesion around the inner border of the left eyelid became more prominent on bending forwards or coughing. A full neurological and systems examination
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
was normal, with no focal motor or sensory deficit involving the left trigeminal nerve. The venous prominences in her mouth had been present since birth, and further oral lesions had appeared in her fourth decade. With time, similar bleb-like lesions appeared all over her body and increased in size. More recently, she had developed lesions on her right hand (figure 1A), on her lip (figure 1B), beneath her tongue (figure 1D) and on her right eyelid. A biopsy suggested a vascular malformation, such as a hamartoma with superadded thrombosis. A CT scan of head and MR brain imaging with angiography showed multiple venous anomalies (figures 2A–D) and venous occlusive disease of the left sylvian fissure and superior sagittal sinus (figure 3). We excluded arteriovenous malformations and dural fistulae with cerebral angiography (figures 2B,C). Following a clinical genetics assessment, we diagnosed blue rubber bleb naevus syndrome. Her symptoms have responded well to low-dose amitriptyline. DISCUSSION Blue rubber bleb naevus syndrome (BRBNS) is rare. It is characterised by multiple cutaneous and visceral venous malformations. First described in 1860, there are only around 200 case reports in the literature.1 Although most appear to be sporadic, some have autosomal-dominant inheritance with linkage to chromosome 9p. The underlying mechanism is not yet known, but tyrosine kinase probably plays a role in venous malformations. The presentation of BRBNS differs with the site of the lesions. ▸ Cutaneous lesions characteristically are dark blue, compressible, rubbery blebs of varying size. They are typically formed by
1
NEUROLOGICAL RARITIES
Figure 1 (A) Venous prominences on right hand, circled in red. (B) Venous prominences on chest, circled in red. (C) Close-up of venous prominences on chest. (D) Venous prominences in oral cavity.
Figure 2 (A–C) Sagittal MRI angiography images illustrating a venous anomaly running down from the sagittal sinus (red arrow). (D) MRI axial T2 image illustrating a venous anomaly adjacent to trigeminal nerve root (red arrow).
2
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
NEUROLOGICAL RARITIES
Figure 3 MRI axial FLAIR image illustrating a left-sided cavernous haemangioma (top red arrow) and aberrant tissue in the expected position of the superior sagittal sinus (bottom red arrow).
a single layer of endothelial cells lining a cavernous space and are separated by fibrous and collagenous tissue. Being of embryonic origin, the venous malformations are present at birth. However, patients may not notice lesions until later in life, as they increase in size and frequency. They may occur anywhere on the body, but are most common on the trunk, limbs and face. They do not appear to bleed spontaneously, but sometimes cause pain or hyperhidrosis. ▸ Extracutaneous lesions include involvement of the gastrointestinal system, bone, heart, lungs, kidneys and the central nervous system (CNS). Their variable location explains a multitude of presentations: the diagnosis of BRBNS may easily be missed. For example, iron deficiency anaemia may result from occult gastrointestinal bleeding. BRBNS also has the potential to cause fatal bleeding; hence its early recognition is important. CNS-associated BRBNS can cause spinal cord compression from multiple extradural venous malformations, right abducens nerve palsy, a dural arteriovenous fistula, epilepsy, progressive ataxia and brainstem signs.
The lesions do not undergo neoplastic change. Treatment is either conservative or more invasive with endoscopy, surgery, steroid laser therapy and sirolimus. Trigeminal neuralgia is usually caused by trigeminal nerve root compression by an aberrant arterial loop, resulting in focal demyelination of the afferent trigeminal nerve fibres and close apposition of demyelinated axons. Venous loops may also be implicated. This local effect on the nerve is thought to result in the spontaneous production of impulses, as well as ephaptic conduction.2 In this patient, the hemifacial pain probably resulted from transient compression of the trigeminal root entry zone, occurring only when there is increased intracranial venous filling during Valsalva or postural change. This differs in character from typical trigeminal neuralgia (ie, not lancinating and brief ) in that the substrate is venous rather than arterial. CONCLUSION BRBNS is a rare vascular disorder with CNS involvement. A neurological examination should include a search for cutaneous lesions and these considered in the differential diagnosis. Our case also highlights an interesting association between transient trigeminal root compression or irritation and hemifacial pain. Acknowledgements The authors are grateful to the patient for permission to publish this case report. Contributors RW-T is the lead author and main contributor. The other authors have all equally contributed to the manuscript and have read and approved it. Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Mark Manford, Cambridge, UK.
REFERENCES
Wynford-Thomas R, et al. Pract Neurol 2014;0:1–3. doi:10.1136/practneurol-2013-000725
1 Nahm WK, Moise S, Eichenfield LF, et al. Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. J Am Acad Dermatol 2004;50:101–6. 2 Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis. Brain 2001;124:2347–60.
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