Clinical Neurology and Neurosurgery 143 (2016) 104–106
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Case report: Superficial siderosis after brachial plexus avulsion T. Decramer a,∗ , T. Theys a , C. Smetcoren b , J. van Loon a , V. Thijs c,d a
Department of Neurosurgery, University Hospitals Leuven, Belgium Department of Neurology, University Hospitals Leuven, Belgium c KU Leuven, Department of Neurosciences, Experimental Neurology, B-3000 Leuven, Belgium d VIB—Vesalius Research Center, University Hospitals Leuven, Department of Neurology, Leuven B-3000, Belgium b
a r t i c l e
i n f o
Article history: Received 6 October 2015 Received in revised form 10 November 2015 Accepted 23 November 2015 Available online 20 February 2016 Keywords: Brachial plexus avulsion Cerebrospinal fluid Hemosiderin Pseudomeningocoele Superficial siderosis
1. Introduction
2. Case report
Superficial siderosis is a slow but progressive neurodegenerative disease caused by a chronic bleed in the subarachnoid space, resulting in hemosiderin deposition alongside the central nervous system [1]. Bilateral sensorineural hearing loss, ataxia and pyramidal signs are the most common symptoms, the diagnosis is confirmed by MRI showing hemosiderin deposition as a dark hypointense layer on T2 and gradient-echo sequences. Superficial siderosis is rare with currently no medical treatment available. Surgery has been proposed to stop disease progression, if the bleeding source can be identified. In this report we illustrate and discuss the association between brachial plexus injury and the development of superficial siderosis and stress the importance of early diagnosis and surgical referral. Is is important to distinguish this case with global superficial siderosis from localized cortical superficial siderosis which is more prevelant and is emerging as a key feature of cerebral amyloid angiopathy [2].
A 60-year old male presented to our outpatient clinic with complaints of balance and gait disturbances for one year. Detailed history revealed decreased sense of smell, taste and progressive bilateral hearing loss with tinnitus over the last years. Twenty years earlier the patient sustained a brachial plexus injury in a car accident, resulting in a paresis of his right arm. His medical history was otherwise unremarkable. Neurological examination showed a mild, generalized ataxia. No other focal signs were present. Magnetic resonance imaging (MRI) of the brain showed extensive global hemosiderin deposition on the surface of the cerebellum, brainstem, cranial nerves and basal cortical structures (Fig. 1), diagnostic for superficial siderosis. Lumbar puncture revealed xanthochromia, indicating recent bleeding. Intra-arterial digital subtraction angiography did not demonstrate any vascular abnormalities of the brain and spinal cord. MRI of the cervical spine showed pseudomeningoceles (PMC), indicative of a previous brachial plexus avulsion. (Fig. 2). Superficial siderosis was attributed to chronic bleeds from friable scar tissue in and around the cervical pseudomeningoceles. Therefore a posterior cervical laminectomy was performed and a tissue graft was placed to close the pseudomeningoceles, in order to stop disease progression. Postoperatively however the patient developed an asymptomatic syrinx in the mid cervical spine, pos-
∗ Corresponding author at: Department of Neurosurgery, Herestraat 49, B-3000 Leuven, Belgium. Fax: +32 16 344241. E-mail address: [email protected] (T. Decramer). http://dx.doi.org/10.1016/j.clineuro.2015.11.020 0303-8467/© 2016 Elsevier B.V. All rights reserved.
T. Decramer et al. / Clinical Neurology and Neurosurgery 143 (2016) 104–106
105
Fig. 1. MR of the brain showing extensive hypo-intensities along the brainstem, cerebellum and cortex. (A) Gradient echo weighted axial image at the level of the pons and cerebellum. (B) Gradient echo weighted axial image at level of the insula. (C) T2-weighted detail axial image at the level of the mesencephalon.
Fig. 2. MR myelographic image of the cervical spine showing bilateral pseudomeningoceles after brachial plexus injury. (A) Coronal view. (B) Oblique view showing pronounced right-sided pseudomeningoceles (arrowheads).
sibly due to local interference in the CSF circulation caused by the tissue graft. One year after surgery there was no clear benefit of the procedure.
3. Discussion Superficial siderosis is a rare, neurodegenerative disease resulting from chronic iron deposition on the surface of neuronal tissues that are in contact with cerebrospinal fluid. Hamill first described siderosis on autopsy as “melanosis” of the brain in 1908 [3]. Although the introduction of MRI in clinical practice has led to a higher detection rate, global superficial siderosis is still a rare condition with around 300 cases presented worldwide [1]. Gradient-echo MR or classic T2 MR sequences have a good sensitivity in detecting hemosiderin depositions as a dark hypointense layer.
Bilateral sensorineural hearing loss occurs in almost all patients and is seen as the cardinal symptom of the disease, followed by ataxia and pyramidal signs. These three symptoms are often called the classic triad of superficial siderosis [4]. The most common underlying cause is chronic bleeding in the subarachnoid space (e.g. due to tumors, stroke, vascular abnormalities, trauma etc.). It is important to search for underlying and potential treatable conditions, such as spinal ependymoma which can be easily excluded by performing an MRI of the full neuroaxis [5]. However, in up to 50% of all described cases the source of bleeding is never found [6]. In nearly all patients undergoing CSF examination, there is evidence of active bleeding by the presence of blood or xanthochromia [6]. Brachial plexus injury as a cause of superficial siderosis is extremely rare with about 14 cases reported in the literature. Symptom onset typically occurs years after the injury, with a median onset of 17 years. The course of the disease is insidious but
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T. Decramer et al. / Clinical Neurology and Neurosurgery 143 (2016) 104–106
progressive and severe neurological impairment can occur. Cervical MRI shows traumatic anatomic changes in 75% of patients, and pseudomeningoceles are the most common finding [7]. Pseudomeningoceles are defined as a collection of extradural CSF resulting from a dural tear. The most frequent cause is iatrogenic, due to spinal surgery. PMCs can also occur posttraumatically after brachial plexus injury [8]. The mechanism by which these pseudomeningoceles can cause chronic bleeding in the subarachnoid space remains unclear but may be due to friable granulation and scar tissue formation after the injury [9]. The distribution of hemosiderin deposition is strikingly similar among patients: the vestibulocochlear nerve, the cerebellum, the brainstem, the olfactory nerve and other basal brain structures are most often affected. This is explained by two distinct hypothetical mechanisms. First, pooling of CSF in de posterior fossa and basal cisterns leads to increased exposure of these structures to hemosiderin. Structures most exposed are most affected. A second explanation relates to the special characteristics of the vestibulocochlear nerve. In most cranial nerves, the transition point between central and peripheral myelin lies in close proximity to the brainstem; the vestibulocochlear nerve on the contrary this transition point is located near the internal acoustic meatus, resulting in a long cisternal tract with only a thin and delicate central myelin insulation along its course through the CSF [6]. Both the olfactory and the optic nerve are essentially central structures, with central myelin insulation. Although not always resulting in anosmia, the olfactory nerve is often affected in superficial siderosis. The optic nerve is also affected resulting in prolonged visually evoked potentials (VEP), visual disturbance however is rare [10]. The central myelin insulation of the brain and specific cranial nerves is considered essential in the pathogenesis of siderosis given the hypothesis that iron-induced damage is thought to be mediated by oligodendrocytes, leading to a disturbance in the finely regulated iron metabolism of the brain, causing neurotoxicity and cell death [11]. Superficial siderosis does not develop from a systemic iron overload, and other iron accumulation disorders of the brain (e.g., mutations in the ferritin pathway, aceruloplasminemia etc.) are clinically distinct from superficial siderosis, suggesting an important role for the CSF in distributing the iron in the latter. The nature of superficial siderosis is slow and progressive and no medical treatment is available. Iron chelation therapy was considered unsuccessful because systemic iron overload is not present in siderosis. However, one case report described clinical improvement with deferiprone, a new iron chelation therapy that can penetrate the blood-brain barrier [12]. Surgery has been proposed if the source of bleeding can be identified. Limited evidence suggests that surgery can stop disease progression, which stresses the importance of an early diagnosis [9]. No long-term follow-up has been reported to see if brain plasticity can result in improvement after surgery.
4. Conclusion Superficial siderosis is a rare neurodegenerative disorder occurring after chronic bleeding in the subarachnoid space due to different underlying neurological conditions. MRI of the brain is the golden standard in the diagnosis of iron deposition along basal brain structures. In patients with a history of brachial plexus injury a high index of suspicion is warranted if such patients present with new neurological symptoms years after the initial injury. Competing interests None. Sources of funding None. Acknowledgments All persons who contributed to this article are listed as coauthors. References [1] N. Kumar, et al., Superficial siderosis, Neurology 66 (2006) 1144–1152, http:// dx.doi.org/10.1212/01.wnl.0000208510.76323.5b. [2] A. Charidimou, et al., Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions, Brain 138 (2015) 2126–2139, http://dx.doi.org/10.1093/brain/awv162. [3] Hamill, Report of a case of melanosis of the brain, cord and meninges, J. Nerv. Ment. Dis. 8 (1908) 594. [4] J.M. Fearnley, J.M. Stevens, P. Rudge, Superficial siderosis of the central nervous system, Brain 118 (Pt. 4) (1995) 1051–1066. [5] S. Pikis, et al., Superficial siderosis of the central nervous system secondary to spinal ependymoma, J. Clin. Neurosci. 21 (2014) 2017–2019, http://dx.doi. org/10.1016/j.jocn.2014.05.020. [6] M. Bracchi, et al., Superficial siderosis of the CNS: MR diagnosis and clinical findings, AJNR Am. J. Neuroradiol. 14 (1993) 227–236. [7] F. Tari-Capone, A. Bozzao, G. Sette, R. Delfini, G. Antonini, Superficial siderosis of central nervous system in patients with brachial plexus injury, Neurol. Sci. 34 (2013) 1861–1865, http://dx.doi.org/10.1007/s10072-013-1336-6. [8] M.W. Hawk, K.D. Kim, Review of spinal pseudomeningoceles and cerebrospinal fluid fistulas, Neurosurg. Focus 9 (2000) e5. [9] K. Aquilina, R. Kumar, J. Lu, D. Rawluk, Superficial siderosis of the central nervous system following cervical nerve root avulsion: the importance of early diagnosis and surgery, Acta Neurochir. (Wien) 147 (2005) 291–297, http://dx.doi.org/10.1007/s00701-004-0460-8, discussion 297. [10] S.L. Painter, L. Mathew, G. Quaghebeur, M.M. Esiri, J.S. Elston, Optic neuropathy in superficial intracranial siderosis, J. Neuroophthalmol. 30 (2010) 311–314, http://dx.doi.org/10.1097/WNO.0b013e3181e92c80. [11] S. Nanda, S.G. Sharma, S. Longo, Superficial siderosis—mechanism of disease: an alternative hypothesis, Ann. Clin. Biochem. 47 (2010) 275–278, http://dx. doi.org/10.1258/acb.2010.009226. [12] G. Cummins, G. Crundwell, D. Baguley, G. Lennox, Treatment of superficial siderosis with iron chelation therapy, BMJ Case Rep. (2013), http://dx.doi.org/ 10.1136/bcr-2013-009916.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Case report: Superficial siderosis after brachial plexus avulsion T. Decramer a,∗ , T. Theys a , C. Smetcoren b , J. van Loon a , V. Thijs c,d a
Department of Neurosurgery, University Hospitals Leuven, Belgium Department of Neurology, University Hospitals Leuven, Belgium c KU Leuven, Department of Neurosciences, Experimental Neurology, B-3000 Leuven, Belgium d VIB—Vesalius Research Center, University Hospitals Leuven, Department of Neurology, Leuven B-3000, Belgium b
a r t i c l e
i n f o
Article history: Received 6 October 2015 Received in revised form 10 November 2015 Accepted 23 November 2015 Available online 20 February 2016 Keywords: Brachial plexus avulsion Cerebrospinal fluid Hemosiderin Pseudomeningocoele Superficial siderosis
1. Introduction
2. Case report
Superficial siderosis is a slow but progressive neurodegenerative disease caused by a chronic bleed in the subarachnoid space, resulting in hemosiderin deposition alongside the central nervous system [1]. Bilateral sensorineural hearing loss, ataxia and pyramidal signs are the most common symptoms, the diagnosis is confirmed by MRI showing hemosiderin deposition as a dark hypointense layer on T2 and gradient-echo sequences. Superficial siderosis is rare with currently no medical treatment available. Surgery has been proposed to stop disease progression, if the bleeding source can be identified. In this report we illustrate and discuss the association between brachial plexus injury and the development of superficial siderosis and stress the importance of early diagnosis and surgical referral. Is is important to distinguish this case with global superficial siderosis from localized cortical superficial siderosis which is more prevelant and is emerging as a key feature of cerebral amyloid angiopathy [2].
A 60-year old male presented to our outpatient clinic with complaints of balance and gait disturbances for one year. Detailed history revealed decreased sense of smell, taste and progressive bilateral hearing loss with tinnitus over the last years. Twenty years earlier the patient sustained a brachial plexus injury in a car accident, resulting in a paresis of his right arm. His medical history was otherwise unremarkable. Neurological examination showed a mild, generalized ataxia. No other focal signs were present. Magnetic resonance imaging (MRI) of the brain showed extensive global hemosiderin deposition on the surface of the cerebellum, brainstem, cranial nerves and basal cortical structures (Fig. 1), diagnostic for superficial siderosis. Lumbar puncture revealed xanthochromia, indicating recent bleeding. Intra-arterial digital subtraction angiography did not demonstrate any vascular abnormalities of the brain and spinal cord. MRI of the cervical spine showed pseudomeningoceles (PMC), indicative of a previous brachial plexus avulsion. (Fig. 2). Superficial siderosis was attributed to chronic bleeds from friable scar tissue in and around the cervical pseudomeningoceles. Therefore a posterior cervical laminectomy was performed and a tissue graft was placed to close the pseudomeningoceles, in order to stop disease progression. Postoperatively however the patient developed an asymptomatic syrinx in the mid cervical spine, pos-
∗ Corresponding author at: Department of Neurosurgery, Herestraat 49, B-3000 Leuven, Belgium. Fax: +32 16 344241. E-mail address: [email protected] (T. Decramer). http://dx.doi.org/10.1016/j.clineuro.2015.11.020 0303-8467/© 2016 Elsevier B.V. All rights reserved.
T. Decramer et al. / Clinical Neurology and Neurosurgery 143 (2016) 104–106
105
Fig. 1. MR of the brain showing extensive hypo-intensities along the brainstem, cerebellum and cortex. (A) Gradient echo weighted axial image at the level of the pons and cerebellum. (B) Gradient echo weighted axial image at level of the insula. (C) T2-weighted detail axial image at the level of the mesencephalon.
Fig. 2. MR myelographic image of the cervical spine showing bilateral pseudomeningoceles after brachial plexus injury. (A) Coronal view. (B) Oblique view showing pronounced right-sided pseudomeningoceles (arrowheads).
sibly due to local interference in the CSF circulation caused by the tissue graft. One year after surgery there was no clear benefit of the procedure.
3. Discussion Superficial siderosis is a rare, neurodegenerative disease resulting from chronic iron deposition on the surface of neuronal tissues that are in contact with cerebrospinal fluid. Hamill first described siderosis on autopsy as “melanosis” of the brain in 1908 [3]. Although the introduction of MRI in clinical practice has led to a higher detection rate, global superficial siderosis is still a rare condition with around 300 cases presented worldwide [1]. Gradient-echo MR or classic T2 MR sequences have a good sensitivity in detecting hemosiderin depositions as a dark hypointense layer.
Bilateral sensorineural hearing loss occurs in almost all patients and is seen as the cardinal symptom of the disease, followed by ataxia and pyramidal signs. These three symptoms are often called the classic triad of superficial siderosis [4]. The most common underlying cause is chronic bleeding in the subarachnoid space (e.g. due to tumors, stroke, vascular abnormalities, trauma etc.). It is important to search for underlying and potential treatable conditions, such as spinal ependymoma which can be easily excluded by performing an MRI of the full neuroaxis [5]. However, in up to 50% of all described cases the source of bleeding is never found [6]. In nearly all patients undergoing CSF examination, there is evidence of active bleeding by the presence of blood or xanthochromia [6]. Brachial plexus injury as a cause of superficial siderosis is extremely rare with about 14 cases reported in the literature. Symptom onset typically occurs years after the injury, with a median onset of 17 years. The course of the disease is insidious but
106
T. Decramer et al. / Clinical Neurology and Neurosurgery 143 (2016) 104–106
progressive and severe neurological impairment can occur. Cervical MRI shows traumatic anatomic changes in 75% of patients, and pseudomeningoceles are the most common finding [7]. Pseudomeningoceles are defined as a collection of extradural CSF resulting from a dural tear. The most frequent cause is iatrogenic, due to spinal surgery. PMCs can also occur posttraumatically after brachial plexus injury [8]. The mechanism by which these pseudomeningoceles can cause chronic bleeding in the subarachnoid space remains unclear but may be due to friable granulation and scar tissue formation after the injury [9]. The distribution of hemosiderin deposition is strikingly similar among patients: the vestibulocochlear nerve, the cerebellum, the brainstem, the olfactory nerve and other basal brain structures are most often affected. This is explained by two distinct hypothetical mechanisms. First, pooling of CSF in de posterior fossa and basal cisterns leads to increased exposure of these structures to hemosiderin. Structures most exposed are most affected. A second explanation relates to the special characteristics of the vestibulocochlear nerve. In most cranial nerves, the transition point between central and peripheral myelin lies in close proximity to the brainstem; the vestibulocochlear nerve on the contrary this transition point is located near the internal acoustic meatus, resulting in a long cisternal tract with only a thin and delicate central myelin insulation along its course through the CSF [6]. Both the olfactory and the optic nerve are essentially central structures, with central myelin insulation. Although not always resulting in anosmia, the olfactory nerve is often affected in superficial siderosis. The optic nerve is also affected resulting in prolonged visually evoked potentials (VEP), visual disturbance however is rare [10]. The central myelin insulation of the brain and specific cranial nerves is considered essential in the pathogenesis of siderosis given the hypothesis that iron-induced damage is thought to be mediated by oligodendrocytes, leading to a disturbance in the finely regulated iron metabolism of the brain, causing neurotoxicity and cell death [11]. Superficial siderosis does not develop from a systemic iron overload, and other iron accumulation disorders of the brain (e.g., mutations in the ferritin pathway, aceruloplasminemia etc.) are clinically distinct from superficial siderosis, suggesting an important role for the CSF in distributing the iron in the latter. The nature of superficial siderosis is slow and progressive and no medical treatment is available. Iron chelation therapy was considered unsuccessful because systemic iron overload is not present in siderosis. However, one case report described clinical improvement with deferiprone, a new iron chelation therapy that can penetrate the blood-brain barrier [12]. Surgery has been proposed if the source of bleeding can be identified. Limited evidence suggests that surgery can stop disease progression, which stresses the importance of an early diagnosis [9]. No long-term follow-up has been reported to see if brain plasticity can result in improvement after surgery.
4. Conclusion Superficial siderosis is a rare neurodegenerative disorder occurring after chronic bleeding in the subarachnoid space due to different underlying neurological conditions. MRI of the brain is the golden standard in the diagnosis of iron deposition along basal brain structures. In patients with a history of brachial plexus injury a high index of suspicion is warranted if such patients present with new neurological symptoms years after the initial injury. Competing interests None. Sources of funding None. Acknowledgments All persons who contributed to this article are listed as coauthors. References [1] N. Kumar, et al., Superficial siderosis, Neurology 66 (2006) 1144–1152, http:// dx.doi.org/10.1212/01.wnl.0000208510.76323.5b. [2] A. Charidimou, et al., Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions, Brain 138 (2015) 2126–2139, http://dx.doi.org/10.1093/brain/awv162. [3] Hamill, Report of a case of melanosis of the brain, cord and meninges, J. Nerv. Ment. Dis. 8 (1908) 594. [4] J.M. Fearnley, J.M. Stevens, P. Rudge, Superficial siderosis of the central nervous system, Brain 118 (Pt. 4) (1995) 1051–1066. [5] S. Pikis, et al., Superficial siderosis of the central nervous system secondary to spinal ependymoma, J. Clin. Neurosci. 21 (2014) 2017–2019, http://dx.doi. org/10.1016/j.jocn.2014.05.020. [6] M. Bracchi, et al., Superficial siderosis of the CNS: MR diagnosis and clinical findings, AJNR Am. J. Neuroradiol. 14 (1993) 227–236. [7] F. Tari-Capone, A. Bozzao, G. Sette, R. Delfini, G. Antonini, Superficial siderosis of central nervous system in patients with brachial plexus injury, Neurol. Sci. 34 (2013) 1861–1865, http://dx.doi.org/10.1007/s10072-013-1336-6. [8] M.W. Hawk, K.D. Kim, Review of spinal pseudomeningoceles and cerebrospinal fluid fistulas, Neurosurg. Focus 9 (2000) e5. [9] K. Aquilina, R. Kumar, J. Lu, D. Rawluk, Superficial siderosis of the central nervous system following cervical nerve root avulsion: the importance of early diagnosis and surgery, Acta Neurochir. (Wien) 147 (2005) 291–297, http://dx.doi.org/10.1007/s00701-004-0460-8, discussion 297. [10] S.L. Painter, L. Mathew, G. Quaghebeur, M.M. Esiri, J.S. Elston, Optic neuropathy in superficial intracranial siderosis, J. Neuroophthalmol. 30 (2010) 311–314, http://dx.doi.org/10.1097/WNO.0b013e3181e92c80. [11] S. Nanda, S.G. Sharma, S. Longo, Superficial siderosis—mechanism of disease: an alternative hypothesis, Ann. Clin. Biochem. 47 (2010) 275–278, http://dx. doi.org/10.1258/acb.2010.009226. [12] G. Cummins, G. Crundwell, D. Baguley, G. Lennox, Treatment of superficial siderosis with iron chelation therapy, BMJ Case Rep. (2013), http://dx.doi.org/ 10.1136/bcr-2013-009916.
