Brief Communication
Stroke-like Phenomena Revealing Multifocal Cerebral Vasculitis in Pediatric Lyme Neuroborreliosis
Journal of Child Neurology 2015, Vol. 30(9) 1226-1229 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814552104 jcn.sagepub.com
Mary Kurian, MD1, Vitor Mendes Pereira, MD2, Maria Isabel Vargas, MD2, and Joel Fluss, MD1
Abstract Stroke-like presentation in Lyme neuroborreliosis is rare in the pediatric age group. We report a previously healthy 12-year-old boy who presented with acute left hemiparesis and meningeal signs. Neuroimaging failed to reveal any cerebral infarction but demonstrated a multifocal cerebral vasculitis involving small, medium and large-sized vessels affecting both the anterior and posterior circulation. Concentric contrast enhancement of the basilar artery was also observed. Further investigations and laboratory findings were consistent with Lyme neuroborreliosis. A rapidly favorable clinical outcome was obtained with appropriate antibiotic treatment along with antiaggregants and steroids. Lyme neuroborreliosis should be considered in the diagnostic differential, not only in adults but also among children, especially in the context of an unexplained cerebral vasculitis. Keywords neuroborreliosis, lyme, vasculitis, stroke, stroke-like, pediatric Received December 31, 2013. Received revised July 25, 2014. Accepted for publication August 20, 2014.
Lyme neuroborreliosis includes a wide range of neurologic manifestations caused by the infection with spirochetes of the Borrelia burgdorferi species. Children with lyme neuroborreliosis most often present with facial nerve palsy or aseptic meningitis; however, other atypical clinical scenarios might be encountered.1 Cerebral vasculitis related to neuroborreliosis has been mainly reported in adult patients subsequent to a meningovascular form of Borrelia infection.2,3 It typically affects the posterior cerebral circulation4 and can either produce definitive stroke or stroke-like symptoms related to transient ischemic lesions and/or to perivascular inflammation.5 Such clinical presentation of Lyme neuroborreliosis in the pediatric age group is exceptional but deserves special attention being a treatable condition.
Case Summary A 12-year-old boy was admitted to the pediatric emergency department with a sudden onset of severe headache, leftsided weakness, unsteadiness, and dysarthria. Further detailed history revealed that he was suffering from intermittent bouts of nausea and vomiting for several months, with increasing frequency (almost daily since the previous 10 days before presentation) and persistent low-grade headache since 4 days. There was a report of tick bites during the preceding summer, but no history of ‘‘erythema migrans.’’ On admission, he was
confused, intermittently disoriented, and complaining of headache; clinical examination revealed a left central facial paresis, mild left hemiparesis, and meningeal signs, but his speech was normal. An emergency computed tomographic (CT) scan did not show any parenchymal changes, but a decrease in the distal collaterals in the right middle cerebral artery territory was observed (Figure 1). Cerebrospinal fluid study revealed marked pleocytosis (1152 leucocytes, 61% neutrophils, 39% lymphocytes), a very high protein content of 4.5 g/L (normal values 0.15-0.45 g/L), and a low glucose level of 0.7 mmol/L (normal values 2.8-4 mmol/L), with slightly elevated blood glucose (8 mmol/L). A brain magnetic resonance imaging (MRI) (1.5 Tesla) performed on day 1 showed subtle narrowing of the left middle cerebral artery and of both anterior cerebral arteries on magnetic resonance angiography, without evidence of associated ischemic parenchymal lesions on diffusion-weighted imaging.
1
Pediatric Neurology, Pediatric Subspecialties Service, Children’s Hospital, Geneva, Switzerland 2 Neuroradiology Unit, University Hospitals, Geneva, Switzerland Corresponding Author: Mary Kurian, MD, Pediatric Neurology, Pediatric Subspecialty Service, University Hospital, Geneva, Rue Willy-Donze´ 6, CH 1211 Geneva 14, Switzerland. Email: [email protected]
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Figure 2. Cerebral 3-dimensional time-of-flight magnetic resonance (MR) sequences of polygon of Willis showing multiple arterial narrowing of the right and left anterior cerebral artery, left middle cerebral artery, and basilar artery (see arrows). Figure 1. Cerebral computed tomographic scan with contrast (multiplanar reconstruction) showing decreased visualization of collaterals in the right middle cerebral artery territory (see arrows).
A broad-spectrum antimicrobial treatment was initiated with ceftriaxone, vancomycin, and acyclovir while waiting for the definitive etiology. Cerebrospinal fluid bacterial cultures remained negative after 48 hours, and PCR was negative for common viruses (HSV 1, 2, varicella-zoster virus, paraechovirus, and enterovirus). On serology studies, anti–Borrelia burgdorferi IgG and IgM antibodies were demonstrated in the serum and anti–Borrelia burgdorferi IgG antibodies in the cerebrospinal fluid. Furthermore, the cerebrospinal fluid /serum Borrelia burgdorferi–specific IgG index antibody ratio was elevated (4.69 for a normal value < 0.25), indicating intrathecal synthesis and establishing the diagnosis of Lyme neuroborreliosis. A specific treatment was then continued with intravenous ceftriaxone alone. The child recovered from the left hemiparesis, and the neurologic exam was normal within 48 hours. Nevertheless, the patient was still complaining of persistent headaches, raising the possibility of an ongoing vasculitis. A transcranial Doppler examination was first performed that showed an acceleration of the blood flow in the circle of Willis at the level of both middle cerebral arteries, left anterior cerebral artery, and left posterior cerebral artery, suggesting a multifocal cerebral vasculitis—later confirmed by a follow-up MRI (3 Tesla) on day 10. Few punctate white matter lesions were identified along with multifocal vessel narrowing involving the left middle cerebral artery, both anterior cerebral arteries, and the distal basilar artery (Figure 2). Furthermore, a concentric vessel wall contrast enhancement was observed at the site of the basilar artery narrowing (Figure 3).
Figure 3. T1-weighted magnetic resonance imaging (MRI) sequences with contrast showing enhancement of the vessel wall of the basilar artery (see arrow).
Prophylactic antiaggregation therapy was initiated with aspirin along with corticosteroids (prednisone) at a dose of 2 mg/kg/d. The clinical improvement was remarkable, with rapid resolution of headache and nausea; the child was back to his normal state within a week and was discharged with a prescription of intravenous ceftriaxone (treatment duration of 4 weeks), aspirin 100 mg/d, and oral prednisone for 4 weeks to be tapered gradually.
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
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Despite remarkable clinical improvement, brain imaging performed 40 days later showed persistent yet stable arterial abnormalities and vessel wall contrast enhancement but no new parenchymal lesion was observed. Treatment was continued with aspirin (3 mg/kg/d) alone. At 1-year follow-up, the patient was asymptomatic and imaging showed no new parenchymal lesion and complete normalization of the cerebral vessels. Aspirin was then stopped. No recurrence of neurologic symptoms was observed in the follow-up.
Discussion Classical neurologic complications of infectious agents include meningitis, encephalitis, abscesses, myelitis, and postinfectious syndromes such as acute disseminated demyelinating encephalomyelitis. There is in addition sufficient evidence now that a large number of pediatric arterial ischemic strokes are also related to infectious factors, through the development of vessel wall injury leading to focal or multifocal vasculopathy/vasculitis rather than through a prothrombotic state6,7 (In the current pediatric stroke literature, the term arteriopathy is used whenever a vessel wall abnormality is detected after AIS and does not presume the nature of the pathology. It is however largely accepted that a true inflammation of the vessel wall [ie, vasculitis] is probably present in many situations where an infectious trigger is identified.) Distinct underlying mechanisms according to the type of the infectious agent have been hypothesized but remain largely speculative in a majority of cases. For instance, varicella-zoster virus probably invades the cerebral arterial vessels through a retrograde axonal transport from the trigeminal ganglion often without causing any diffuse systemic and/or parenchymatous brain involvement.8 In contrast, in many cases of bacterial and fungal infections, the resulting vasculitis is thought to arise from the underlying meningitis through contiguous inflammation of the large arteries forming the circle of Willis, which lies in the interpeduncular cistern filled by an inflammatory cerebrospinal fluid such as in tuberculosis. In Lyme neuroborreliosis, a specific meningovascular involvement with a predominant basal leptomeningeal obliterative inflammatory vasculopathy (endarteritis) very similar to the one found in neurosyphilis has been reported in autopsy specimens.9 In fact, both spirochetes seem to share considerable clinical and neuropathologic features, suggesting similar pathogenic mechanisms and mode of central nervous system invasion.10 Other isolated or coexisting mechanisms, either cytokine mediated or by immune deposition, are also hypothesized and could explain the occurrence of cerebral vasculitis and stroke after more trivial infectious triggers.11 It is therefore important to actively search for a source of infection after pediatric stroke.6 The particular clinical feature in our patient was the absence of a true cerebral infarct, accounting for the label ‘‘stroke-like.’’ This phenomenon, reported in diverse forms of cerebral vasculitis, has been described mostly in adults12 and is an important clue to the diagnosis. Its occurrence in children is to our knowledge exceptional. The pathogenesis of stroke-like phenomena
remains speculative, but likely reflects focal parenchymal brain dysfunction contiguous to small vessel vasculitis (inducing regional brain hypoperfusion) and/or to isolated areas of demyelination related to direct oligodendrocyte damage. In fact, these 2 mechanisms have been described simultaneously in rare histopathologic specimens of patients with neuroborreliosis.13,14 When stroke from cerebral vasculitis is suspected, appropriate radiologic and laboratory investigations need to be rapidly performed in order to determine to confirm the diagnosis and to search for etiology that is either inflammatory or infectious.15 Although a CT scan is still often performed in the emergency setting to rule out brain hemorrhage or mass effect, MRI and magnetic resonance angiography should be preferred in children with acute neurologic deficit as they can detect early ischemic lesions and rapidly assess the anatomy of major cerebral vessels. Vessel wall imaging could add to the evaluation of the affected arteries. In our case described above, the initial CT scan did not show any parenchymal ischemic lesions; it did, however, point to a decreased visualization of the distal collaterals in the right middle cerebral artery territory (Figure 1), a finding that was initially overlooked. The first MRI with a 1.5-Tesla resolution showed minimal evidence of vasculitis, no contrast enhancement, and no parenchymal lesions on diffusion-weighted imaging but a vascular asymmetry with a possible narrowing of the left middle and anterior cerebral arteries. However, the 3-Tesla MRI with angiography repeated after 10 days showed evidence of ischemic white matter lesions bilaterally and multifocal areas of vessel narrowing, along with the vessel wall contrast enhancement of the basilar artery in a clear and well-defined manner.16 However, we acknowledge that the above comparisons between the 2 MRIs are to be interpreted with caution, as both the exams were not done simultaneously. The contrast enhancement of the basilar artery is an important sign pointing to an inflammatory/infectious vasculitis.17 In a recent review, it has been shown that normal periarterial enhancement along major intracranial arteries can be observed in the pediatric age group, but it is rarely observed in segments surrounded by cerebrospinal fluid, including V4 segments of the vertebral artery, and the basilar artery.18 Lebas et al reported an 8-year-old boy with cerebral vasculitis due to Lyme neuroborreliosis, presenting with a right hemispheric stroke (ischemic lesions in the pons and cerebellum, with focal stenosis of the basilar artery on magnetic resonance angiography and focal gadolinium enhancement of the basilar artery wall.19 Although such a finding is certainly not specific, the predilection of lyme neuroborreliosis vasculitis toward the posterior circulation must be again emphasized again and this radiologic sign should probably alert the clinician to consider the possibility of Lyme disease, rather than a varicella vasculopathy in children that involves almost systematically the anterior circulation (usually the M1 segment of the middle cerebral artery).20 Cerebrospinal fluid analysis and serologic studies remain still the most useful investigations to suspect and to confirm Lyme neuroborreliosis. High cerebrospinal fluid protein content and lymphocytic pleocytosis are frequently, if not always,
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
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present in lyme neuroborreliosis21 whereas low glucose is an inconsistent finding. The confirmation of the diagnosis relies on serologic testing and the evidence of intrathecal Borreliaspecific antibody production.21,22 Intravenous antibiotic therapy is indicated for acute neurologic manifestations of Lyme disease, ceftriaxone being the drug of choice.22 Corticosteroids and prophylactic antiaggregants are indicated when there is evidence of ongoing central nervous system vasculitis. With the specific treatment, our patient’s clinical outcome was favorable. No basilar artery contrast enhancement was found at 1-year follow-up imaging. In conclusion, Lyme neuroborreliosis in children might manifest with acute neurologic deficit through a localized or a more diffuse vasculitis. As it is a treatable condition with a good prognosis, a high index of suspicion is needed for early identification. Proper radiologic and laboratory workup should enable rapid diagnostic confirmation. Acknowledgments We acknowledge Prof Sylviane Hanquinet, Head of Pediatric Radiology, who analyzed the initial computed tomographic and magnetic resonance imaging (MRI) scans.
Author Contributions MK prepared the manuscript, reviewed the literature, and was involved in the patient care and follow-up as well as analysis of the data. VMP and MIVG analyzed the images and reviewed the manuscript. JF reviewed the manuscript and was involved in patient care, follow-up, and analysis of images.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
References 1. Baumann M, Birnbacher R, Koch J, Strobl R, Rosta´sy K. Uncommon manifestations of neuroborreliosis in children. Eur J Paediatr Neurol. 2010;14:274-277. 2. Topakian R, Stieglbauer K, Nussbaumer K, Aichner FT. Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge. Cerebrovasc Dis. 2008;26: 455-461. 3. Rey V, Du Pasquier R, Muehl A, et al. Multiple ischemic strokes due to Borrelia garinii meningovasculitis. Rev Neurol (Paris). 2010;166:931-934. 4. Back T, Gru¨nig S, Winter Y, et al. Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life. J Neurol. 2013;260:1569-1575.
5. Re´nard C, Marignier S, Gillet Y, et al. Acute hemiparesis revealing a neuroborreliosis in a child. Arch Pediatr. 2008;15:41-44. 6. Amlie-Lefond C, Fullerton HJ. Rashes, sniffles, and stroke: a role for infection in ischemic stroke of childhood. Infect Disord Drug Targets. 2010;10:67-75. 7. Mineyko A, Narendran A, Fritzler ML, et al. Inflammatory biomarkers of pediatric focal cerebral arteriopathy. Neurology. 2012;79:1406-1408. 8. Nagel MA. Varicella zoster virus vasculopathy: clinical features and pathogenesis. J Neurovirol. 2014;20:157-163. 9. Miklossy J, Kuntzer T, Bogousslavsky J, et al. Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis. Acta Neuropathol. 1990;80:568-572. 10. Miklossy J. Biology and neuropathology of dementia in syphilis and Lyme disease. Handb Clin Neurol. 2008;89:825-844. 11. Fullerton HJ, Elkind MS, Barkovich AJ, et al. The vascular effects of infection in Pediatric Stroke (VIPS) Study. J Child Neurol. 2011;26:1101-1110. 12. Romi F, Kra˚kenes J, Aarli JA, Tysnes OB. Neuroborreliosis with vasculitis causing stroke-like manifestations. Eur Neurol. 2004; 51:49-50. 13. Oksi J, Kalimo H, Martilla RJ, et al. Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain. 1996;119:2143-2154. 14. Fallon BA, Levin ES, Schweitzer PJ, Hardesty D. Inflammation and central nervous system Lyme disease. Neurobiol Dis. 2010; 37:534-541. 15. Moharir M, Shroff M, Benseler SM. Childhood central nervous system vasculitis. Neuroimaging Clin N Am. 2013;23:293-308. 16. Swartz RH, Bhuta SS, Farb RI, et al. Intracranial arterial wall imaging using high-resolution 3-Tesla contrast-enhanced MRI. Neurology. 2009;72:627-634. 17. Ku¨ker W, Gaertner S, Na¨gele T, et al. Vessel wall contrast enhancement: a diagnostic sign of cerebral vasculitis. Cerebrovasc Dis. 2008;26:23-29. 18. Mineyko A, Kirton A, Ng D, Wei XC. Normal intracranial periarterial enhancement on pediatric brain MR imaging. Neuroradiology. 2013;55:1161-1169. 19. Lebas A, Fred’erique Toulgoat F, Guillaume Saliou G, et al. Stroke due to Lyme neuroborreliosis: changes in vessel wall contrast enhancement. J Neuroimaging. 2012;22:210-212. 20. Monteventi O, Chabrier S, Fluss J. Current management of postvaricella stroke in children: a literature review. Arch Pediatr. 2013;20:883-889. 21. Djukic M, Schmidt-Samoa C, Lange P, et al. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012;259:630-636. 22. Mygland A, Ljøstad U, Fingerle V, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010;17:8-16.
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
Stroke-like Phenomena Revealing Multifocal Cerebral Vasculitis in Pediatric Lyme Neuroborreliosis
Journal of Child Neurology 2015, Vol. 30(9) 1226-1229 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814552104 jcn.sagepub.com
Mary Kurian, MD1, Vitor Mendes Pereira, MD2, Maria Isabel Vargas, MD2, and Joel Fluss, MD1
Abstract Stroke-like presentation in Lyme neuroborreliosis is rare in the pediatric age group. We report a previously healthy 12-year-old boy who presented with acute left hemiparesis and meningeal signs. Neuroimaging failed to reveal any cerebral infarction but demonstrated a multifocal cerebral vasculitis involving small, medium and large-sized vessels affecting both the anterior and posterior circulation. Concentric contrast enhancement of the basilar artery was also observed. Further investigations and laboratory findings were consistent with Lyme neuroborreliosis. A rapidly favorable clinical outcome was obtained with appropriate antibiotic treatment along with antiaggregants and steroids. Lyme neuroborreliosis should be considered in the diagnostic differential, not only in adults but also among children, especially in the context of an unexplained cerebral vasculitis. Keywords neuroborreliosis, lyme, vasculitis, stroke, stroke-like, pediatric Received December 31, 2013. Received revised July 25, 2014. Accepted for publication August 20, 2014.
Lyme neuroborreliosis includes a wide range of neurologic manifestations caused by the infection with spirochetes of the Borrelia burgdorferi species. Children with lyme neuroborreliosis most often present with facial nerve palsy or aseptic meningitis; however, other atypical clinical scenarios might be encountered.1 Cerebral vasculitis related to neuroborreliosis has been mainly reported in adult patients subsequent to a meningovascular form of Borrelia infection.2,3 It typically affects the posterior cerebral circulation4 and can either produce definitive stroke or stroke-like symptoms related to transient ischemic lesions and/or to perivascular inflammation.5 Such clinical presentation of Lyme neuroborreliosis in the pediatric age group is exceptional but deserves special attention being a treatable condition.
Case Summary A 12-year-old boy was admitted to the pediatric emergency department with a sudden onset of severe headache, leftsided weakness, unsteadiness, and dysarthria. Further detailed history revealed that he was suffering from intermittent bouts of nausea and vomiting for several months, with increasing frequency (almost daily since the previous 10 days before presentation) and persistent low-grade headache since 4 days. There was a report of tick bites during the preceding summer, but no history of ‘‘erythema migrans.’’ On admission, he was
confused, intermittently disoriented, and complaining of headache; clinical examination revealed a left central facial paresis, mild left hemiparesis, and meningeal signs, but his speech was normal. An emergency computed tomographic (CT) scan did not show any parenchymal changes, but a decrease in the distal collaterals in the right middle cerebral artery territory was observed (Figure 1). Cerebrospinal fluid study revealed marked pleocytosis (1152 leucocytes, 61% neutrophils, 39% lymphocytes), a very high protein content of 4.5 g/L (normal values 0.15-0.45 g/L), and a low glucose level of 0.7 mmol/L (normal values 2.8-4 mmol/L), with slightly elevated blood glucose (8 mmol/L). A brain magnetic resonance imaging (MRI) (1.5 Tesla) performed on day 1 showed subtle narrowing of the left middle cerebral artery and of both anterior cerebral arteries on magnetic resonance angiography, without evidence of associated ischemic parenchymal lesions on diffusion-weighted imaging.
1
Pediatric Neurology, Pediatric Subspecialties Service, Children’s Hospital, Geneva, Switzerland 2 Neuroradiology Unit, University Hospitals, Geneva, Switzerland Corresponding Author: Mary Kurian, MD, Pediatric Neurology, Pediatric Subspecialty Service, University Hospital, Geneva, Rue Willy-Donze´ 6, CH 1211 Geneva 14, Switzerland. Email: [email protected]
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
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Figure 2. Cerebral 3-dimensional time-of-flight magnetic resonance (MR) sequences of polygon of Willis showing multiple arterial narrowing of the right and left anterior cerebral artery, left middle cerebral artery, and basilar artery (see arrows). Figure 1. Cerebral computed tomographic scan with contrast (multiplanar reconstruction) showing decreased visualization of collaterals in the right middle cerebral artery territory (see arrows).
A broad-spectrum antimicrobial treatment was initiated with ceftriaxone, vancomycin, and acyclovir while waiting for the definitive etiology. Cerebrospinal fluid bacterial cultures remained negative after 48 hours, and PCR was negative for common viruses (HSV 1, 2, varicella-zoster virus, paraechovirus, and enterovirus). On serology studies, anti–Borrelia burgdorferi IgG and IgM antibodies were demonstrated in the serum and anti–Borrelia burgdorferi IgG antibodies in the cerebrospinal fluid. Furthermore, the cerebrospinal fluid /serum Borrelia burgdorferi–specific IgG index antibody ratio was elevated (4.69 for a normal value < 0.25), indicating intrathecal synthesis and establishing the diagnosis of Lyme neuroborreliosis. A specific treatment was then continued with intravenous ceftriaxone alone. The child recovered from the left hemiparesis, and the neurologic exam was normal within 48 hours. Nevertheless, the patient was still complaining of persistent headaches, raising the possibility of an ongoing vasculitis. A transcranial Doppler examination was first performed that showed an acceleration of the blood flow in the circle of Willis at the level of both middle cerebral arteries, left anterior cerebral artery, and left posterior cerebral artery, suggesting a multifocal cerebral vasculitis—later confirmed by a follow-up MRI (3 Tesla) on day 10. Few punctate white matter lesions were identified along with multifocal vessel narrowing involving the left middle cerebral artery, both anterior cerebral arteries, and the distal basilar artery (Figure 2). Furthermore, a concentric vessel wall contrast enhancement was observed at the site of the basilar artery narrowing (Figure 3).
Figure 3. T1-weighted magnetic resonance imaging (MRI) sequences with contrast showing enhancement of the vessel wall of the basilar artery (see arrow).
Prophylactic antiaggregation therapy was initiated with aspirin along with corticosteroids (prednisone) at a dose of 2 mg/kg/d. The clinical improvement was remarkable, with rapid resolution of headache and nausea; the child was back to his normal state within a week and was discharged with a prescription of intravenous ceftriaxone (treatment duration of 4 weeks), aspirin 100 mg/d, and oral prednisone for 4 weeks to be tapered gradually.
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
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Journal of Child Neurology 30(9)
Despite remarkable clinical improvement, brain imaging performed 40 days later showed persistent yet stable arterial abnormalities and vessel wall contrast enhancement but no new parenchymal lesion was observed. Treatment was continued with aspirin (3 mg/kg/d) alone. At 1-year follow-up, the patient was asymptomatic and imaging showed no new parenchymal lesion and complete normalization of the cerebral vessels. Aspirin was then stopped. No recurrence of neurologic symptoms was observed in the follow-up.
Discussion Classical neurologic complications of infectious agents include meningitis, encephalitis, abscesses, myelitis, and postinfectious syndromes such as acute disseminated demyelinating encephalomyelitis. There is in addition sufficient evidence now that a large number of pediatric arterial ischemic strokes are also related to infectious factors, through the development of vessel wall injury leading to focal or multifocal vasculopathy/vasculitis rather than through a prothrombotic state6,7 (In the current pediatric stroke literature, the term arteriopathy is used whenever a vessel wall abnormality is detected after AIS and does not presume the nature of the pathology. It is however largely accepted that a true inflammation of the vessel wall [ie, vasculitis] is probably present in many situations where an infectious trigger is identified.) Distinct underlying mechanisms according to the type of the infectious agent have been hypothesized but remain largely speculative in a majority of cases. For instance, varicella-zoster virus probably invades the cerebral arterial vessels through a retrograde axonal transport from the trigeminal ganglion often without causing any diffuse systemic and/or parenchymatous brain involvement.8 In contrast, in many cases of bacterial and fungal infections, the resulting vasculitis is thought to arise from the underlying meningitis through contiguous inflammation of the large arteries forming the circle of Willis, which lies in the interpeduncular cistern filled by an inflammatory cerebrospinal fluid such as in tuberculosis. In Lyme neuroborreliosis, a specific meningovascular involvement with a predominant basal leptomeningeal obliterative inflammatory vasculopathy (endarteritis) very similar to the one found in neurosyphilis has been reported in autopsy specimens.9 In fact, both spirochetes seem to share considerable clinical and neuropathologic features, suggesting similar pathogenic mechanisms and mode of central nervous system invasion.10 Other isolated or coexisting mechanisms, either cytokine mediated or by immune deposition, are also hypothesized and could explain the occurrence of cerebral vasculitis and stroke after more trivial infectious triggers.11 It is therefore important to actively search for a source of infection after pediatric stroke.6 The particular clinical feature in our patient was the absence of a true cerebral infarct, accounting for the label ‘‘stroke-like.’’ This phenomenon, reported in diverse forms of cerebral vasculitis, has been described mostly in adults12 and is an important clue to the diagnosis. Its occurrence in children is to our knowledge exceptional. The pathogenesis of stroke-like phenomena
remains speculative, but likely reflects focal parenchymal brain dysfunction contiguous to small vessel vasculitis (inducing regional brain hypoperfusion) and/or to isolated areas of demyelination related to direct oligodendrocyte damage. In fact, these 2 mechanisms have been described simultaneously in rare histopathologic specimens of patients with neuroborreliosis.13,14 When stroke from cerebral vasculitis is suspected, appropriate radiologic and laboratory investigations need to be rapidly performed in order to determine to confirm the diagnosis and to search for etiology that is either inflammatory or infectious.15 Although a CT scan is still often performed in the emergency setting to rule out brain hemorrhage or mass effect, MRI and magnetic resonance angiography should be preferred in children with acute neurologic deficit as they can detect early ischemic lesions and rapidly assess the anatomy of major cerebral vessels. Vessel wall imaging could add to the evaluation of the affected arteries. In our case described above, the initial CT scan did not show any parenchymal ischemic lesions; it did, however, point to a decreased visualization of the distal collaterals in the right middle cerebral artery territory (Figure 1), a finding that was initially overlooked. The first MRI with a 1.5-Tesla resolution showed minimal evidence of vasculitis, no contrast enhancement, and no parenchymal lesions on diffusion-weighted imaging but a vascular asymmetry with a possible narrowing of the left middle and anterior cerebral arteries. However, the 3-Tesla MRI with angiography repeated after 10 days showed evidence of ischemic white matter lesions bilaterally and multifocal areas of vessel narrowing, along with the vessel wall contrast enhancement of the basilar artery in a clear and well-defined manner.16 However, we acknowledge that the above comparisons between the 2 MRIs are to be interpreted with caution, as both the exams were not done simultaneously. The contrast enhancement of the basilar artery is an important sign pointing to an inflammatory/infectious vasculitis.17 In a recent review, it has been shown that normal periarterial enhancement along major intracranial arteries can be observed in the pediatric age group, but it is rarely observed in segments surrounded by cerebrospinal fluid, including V4 segments of the vertebral artery, and the basilar artery.18 Lebas et al reported an 8-year-old boy with cerebral vasculitis due to Lyme neuroborreliosis, presenting with a right hemispheric stroke (ischemic lesions in the pons and cerebellum, with focal stenosis of the basilar artery on magnetic resonance angiography and focal gadolinium enhancement of the basilar artery wall.19 Although such a finding is certainly not specific, the predilection of lyme neuroborreliosis vasculitis toward the posterior circulation must be again emphasized again and this radiologic sign should probably alert the clinician to consider the possibility of Lyme disease, rather than a varicella vasculopathy in children that involves almost systematically the anterior circulation (usually the M1 segment of the middle cerebral artery).20 Cerebrospinal fluid analysis and serologic studies remain still the most useful investigations to suspect and to confirm Lyme neuroborreliosis. High cerebrospinal fluid protein content and lymphocytic pleocytosis are frequently, if not always,
Downloaded from jcn.sagepub.com at UNIV OF WINNIPEG on August 8, 2015
Kurian et al
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present in lyme neuroborreliosis21 whereas low glucose is an inconsistent finding. The confirmation of the diagnosis relies on serologic testing and the evidence of intrathecal Borreliaspecific antibody production.21,22 Intravenous antibiotic therapy is indicated for acute neurologic manifestations of Lyme disease, ceftriaxone being the drug of choice.22 Corticosteroids and prophylactic antiaggregants are indicated when there is evidence of ongoing central nervous system vasculitis. With the specific treatment, our patient’s clinical outcome was favorable. No basilar artery contrast enhancement was found at 1-year follow-up imaging. In conclusion, Lyme neuroborreliosis in children might manifest with acute neurologic deficit through a localized or a more diffuse vasculitis. As it is a treatable condition with a good prognosis, a high index of suspicion is needed for early identification. Proper radiologic and laboratory workup should enable rapid diagnostic confirmation. Acknowledgments We acknowledge Prof Sylviane Hanquinet, Head of Pediatric Radiology, who analyzed the initial computed tomographic and magnetic resonance imaging (MRI) scans.
Author Contributions MK prepared the manuscript, reviewed the literature, and was involved in the patient care and follow-up as well as analysis of the data. VMP and MIVG analyzed the images and reviewed the manuscript. JF reviewed the manuscript and was involved in patient care, follow-up, and analysis of images.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
References 1. Baumann M, Birnbacher R, Koch J, Strobl R, Rosta´sy K. Uncommon manifestations of neuroborreliosis in children. Eur J Paediatr Neurol. 2010;14:274-277. 2. Topakian R, Stieglbauer K, Nussbaumer K, Aichner FT. Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge. Cerebrovasc Dis. 2008;26: 455-461. 3. Rey V, Du Pasquier R, Muehl A, et al. Multiple ischemic strokes due to Borrelia garinii meningovasculitis. Rev Neurol (Paris). 2010;166:931-934. 4. Back T, Gru¨nig S, Winter Y, et al. Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life. J Neurol. 2013;260:1569-1575.
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