J Neurol (2014) 261:438–440 DOI 10.1007/s00415-013-7217-3
LETTER TO THE EDITORS
Spinal hemorrhage in eosinophilic granulomatosis with polyangiitis (Churg–Strauss) Luca Diamanti • Giulia Berzero • Paola Bini • Sabrina Ravaglia • Elisa Rognone Lorenzo Cavagna • Enrico Marchioni
•
Received: 26 November 2013 / Accepted: 11 December 2013 / Published online: 25 December 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Dear Sirs, Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as a Churg–Strauss syndrome [1], is a rare systemic small vessel vasculitis mainly affecting people aged 40–60 years without gender predominance [2, 3]. Asthma, eosinophilia, chronic paranasal sinusitis, nasal polyposis, non-fixed pulmonary infiltrates, and myocarditis are typical findings of EGPA [4]. Neurologic involvement is frequently observed and peripheral nervous system (PNS) is affected in 59–86 % of patients, mainly in the form of peripheral neuropathy [5]. On the contrary, central nervous system (CNS) involvement is described in less than 10 % of cases [5]. The most common CNS manifestations are cerebral infarction and diffuse encephalopathy, while cerebral hemorrhages have been seldom associated with EGPA [6] and only one case of spinal subarachnoid hemorrhage has been previously reported in the early 1980s [7]. In June of 2012, a 31-year-old pregnant Caucasian woman with a long-term history of asthma and rhinitis on the day of the delivery presented with high spiking fever (up to 39.5 °C) and arthralgias, disappearing in a few L. Diamanti (&) G. Berzero P. Bini S. Ravaglia E. Marchioni Neurology Department, IRCCS National Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy e-mail: [email protected] E. Rognone Neuroradiology Department, IRCCS National Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy L. Cavagna Division of Rheumatology, University and IRCCS Policlinico S. Matteo Foundation, viale Golgi 3, 27100 Pavia, Italy
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hours. Further similar episodes were then observed in the subsequent months without other additional findings. In August 2012, painful paresthesias in left hand, right arm, and dorsal surface of right foot appeared, together with bilateral distal upper limbs weakness. Electromyography/ electroneurography (EMG/ENG) confirmed a severe sensory-motor axonal neuropathy, predominant in upper limbs, characterized by patchy pattern as in vasculitic mononeuritis multiplex. Laboratory investigations showed an increase of inflammatory markers (ESR 58 mm/h, CPR 6.9 mg/dl) and leukocytosis (21,000/ll) with eosinophilia (63 %). Antineutrophil cytoplasmic antibodies (ANCA) were positive both in IIF (p-ANCA pattern) and in ELISA (anti-MPO specificity). Because of headache and neck stiffness appearance, brain MRI was performed, displaying maxillary and sphenoid sinusitis without CNS pathological findings. After the exclusion of underlying infections, the patient was diagnosed with EGPA and methylprednisolone 1 mg/kg/ day i.v. was started. Despite corticosteroid treatment, headache and neck stiffness persisted, global left upper limb weakness worsened in particular arm and wrist extension, and brisk left supinator tendon reflex appeared. Lumbar puncture revealed hemorrhagic cerebrospinal fluid, with a protein value of 755 mg/dl, glucose value of 23 mg/ dl, and 205 cells (neutrophils and red blood cells). HumanCMV and HSV infections were excluded by real-time PCR on cerebrospinal fluid, as well as other infectious processes. Spinal MRI was performed showing cervical and dorsal subarachnoid bleeding with spinal cord compression and C6–C7 intramedullary hyperintensity on the left side (Figs. 1a, 2a). Intravenous steroid (methylprednisolone 1 mg/kg/day i.v. for 6 days) was administered, followed by oral prednisone (75 mg/day) with subsequent tapering until suspension at 12 weeks.
J Neurol (2014) 261:438–440
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Fig. 1 a Sagittal T1-weighted MR image showing intradural linear hyperintensity C6-D2 consistent with ventral subarachnoid bleeding. b Sagittal T1-weighted MR image performed 1 month later showing complete resolution of hemorrhage
Fig. 2 a Axial T1-weighted FAT-SAT MR image showed intradural anterolateral hyperintensity C6–C7 consistent with hemorrhage with left spinal compression. b Axial T1weighted MR image performed 1 month later showing C6–C7 normal findings
Radiological follow-up 1 month later (Figs. 1b, 2b) pointed out a complete disappearance of hemorrhage and spinal compression, with resolution of CNS symptoms and improvement of PNS disturbances; moreover in November 2012 rituximab (500 mg/weekly for 4 weeks every 6 months)
was started. To date, the patient is still in follow-up, prednisone has been tapered until suspension, and rituximab courses are still ongoing with no signs/symptoms of EGPA flares. This case clearly suggested that ANCA-associated vasculitis should be frequently considered in the differential
123
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J Neurol (2014) 261:438–440
diagnosis of neurology disorders. The occurrence of symptoms such as fever, arthralgias, and manifestations such as sinusitis or asthma may be the clue for the right classification of these patients. Conflicts of interest
2.
No conflicts of interest to declare.
Ethical standard This study has been approved by the appropriate ethics committee and has therefore been performed in the accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
3.
4. 5.
References 1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA (2013) 2012 revised International Chapel
123
6.
7.
Hill Consensus Conference Nomenclature of Vasculitides. Arthr Rheum 65:1–11 Moosig F, Bremer JP, Hellmich B, Holle JU, Holl-Ulrich K, Laudien M, Matthis C, Metzler C, No¨lle B, Richardt G, Gross WL (2013) A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg–Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis 72:1011–1017 Piram M, Maldini C, Mahr A (2012) Effect of race/ethnicity on risk, presentation and course of connective tissue diseases and primary systemic vasculitides. Curr Opin Rheumatol 24:193–200 Noth I, Strek ME, Leff AR (2003) Churg-Strauss syndrome. Lancet 361:587–594 Finsterer J (2010) Neurological manifestations of Churg–Strauss syndrome. Eur J Neurol 17:524–525 Mencacci NE, Bersano A, Cinnante CM, Ciammola A, Corti S, Meroni PL, Silani V (2011) Intracerebral haemorrhage, a possible presentation in Churg–Strauss syndrome: case report and review of the literature. J Neurol Sci 301(1–2):107–111 Maloon A, Fritz VU, Kaplan CL (1985) Neurological complications of systemic vasculitis. A report of 2 cases. S Afr Med J 68:603–605
LETTER TO THE EDITORS
Spinal hemorrhage in eosinophilic granulomatosis with polyangiitis (Churg–Strauss) Luca Diamanti • Giulia Berzero • Paola Bini • Sabrina Ravaglia • Elisa Rognone Lorenzo Cavagna • Enrico Marchioni
•
Received: 26 November 2013 / Accepted: 11 December 2013 / Published online: 25 December 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Dear Sirs, Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as a Churg–Strauss syndrome [1], is a rare systemic small vessel vasculitis mainly affecting people aged 40–60 years without gender predominance [2, 3]. Asthma, eosinophilia, chronic paranasal sinusitis, nasal polyposis, non-fixed pulmonary infiltrates, and myocarditis are typical findings of EGPA [4]. Neurologic involvement is frequently observed and peripheral nervous system (PNS) is affected in 59–86 % of patients, mainly in the form of peripheral neuropathy [5]. On the contrary, central nervous system (CNS) involvement is described in less than 10 % of cases [5]. The most common CNS manifestations are cerebral infarction and diffuse encephalopathy, while cerebral hemorrhages have been seldom associated with EGPA [6] and only one case of spinal subarachnoid hemorrhage has been previously reported in the early 1980s [7]. In June of 2012, a 31-year-old pregnant Caucasian woman with a long-term history of asthma and rhinitis on the day of the delivery presented with high spiking fever (up to 39.5 °C) and arthralgias, disappearing in a few L. Diamanti (&) G. Berzero P. Bini S. Ravaglia E. Marchioni Neurology Department, IRCCS National Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy e-mail: [email protected] E. Rognone Neuroradiology Department, IRCCS National Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy L. Cavagna Division of Rheumatology, University and IRCCS Policlinico S. Matteo Foundation, viale Golgi 3, 27100 Pavia, Italy
123
hours. Further similar episodes were then observed in the subsequent months without other additional findings. In August 2012, painful paresthesias in left hand, right arm, and dorsal surface of right foot appeared, together with bilateral distal upper limbs weakness. Electromyography/ electroneurography (EMG/ENG) confirmed a severe sensory-motor axonal neuropathy, predominant in upper limbs, characterized by patchy pattern as in vasculitic mononeuritis multiplex. Laboratory investigations showed an increase of inflammatory markers (ESR 58 mm/h, CPR 6.9 mg/dl) and leukocytosis (21,000/ll) with eosinophilia (63 %). Antineutrophil cytoplasmic antibodies (ANCA) were positive both in IIF (p-ANCA pattern) and in ELISA (anti-MPO specificity). Because of headache and neck stiffness appearance, brain MRI was performed, displaying maxillary and sphenoid sinusitis without CNS pathological findings. After the exclusion of underlying infections, the patient was diagnosed with EGPA and methylprednisolone 1 mg/kg/ day i.v. was started. Despite corticosteroid treatment, headache and neck stiffness persisted, global left upper limb weakness worsened in particular arm and wrist extension, and brisk left supinator tendon reflex appeared. Lumbar puncture revealed hemorrhagic cerebrospinal fluid, with a protein value of 755 mg/dl, glucose value of 23 mg/ dl, and 205 cells (neutrophils and red blood cells). HumanCMV and HSV infections were excluded by real-time PCR on cerebrospinal fluid, as well as other infectious processes. Spinal MRI was performed showing cervical and dorsal subarachnoid bleeding with spinal cord compression and C6–C7 intramedullary hyperintensity on the left side (Figs. 1a, 2a). Intravenous steroid (methylprednisolone 1 mg/kg/day i.v. for 6 days) was administered, followed by oral prednisone (75 mg/day) with subsequent tapering until suspension at 12 weeks.
J Neurol (2014) 261:438–440
439
Fig. 1 a Sagittal T1-weighted MR image showing intradural linear hyperintensity C6-D2 consistent with ventral subarachnoid bleeding. b Sagittal T1-weighted MR image performed 1 month later showing complete resolution of hemorrhage
Fig. 2 a Axial T1-weighted FAT-SAT MR image showed intradural anterolateral hyperintensity C6–C7 consistent with hemorrhage with left spinal compression. b Axial T1weighted MR image performed 1 month later showing C6–C7 normal findings
Radiological follow-up 1 month later (Figs. 1b, 2b) pointed out a complete disappearance of hemorrhage and spinal compression, with resolution of CNS symptoms and improvement of PNS disturbances; moreover in November 2012 rituximab (500 mg/weekly for 4 weeks every 6 months)
was started. To date, the patient is still in follow-up, prednisone has been tapered until suspension, and rituximab courses are still ongoing with no signs/symptoms of EGPA flares. This case clearly suggested that ANCA-associated vasculitis should be frequently considered in the differential
123
440
J Neurol (2014) 261:438–440
diagnosis of neurology disorders. The occurrence of symptoms such as fever, arthralgias, and manifestations such as sinusitis or asthma may be the clue for the right classification of these patients. Conflicts of interest
2.
No conflicts of interest to declare.
Ethical standard This study has been approved by the appropriate ethics committee and has therefore been performed in the accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
3.
4. 5.
References 1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA (2013) 2012 revised International Chapel
123
6.
7.
Hill Consensus Conference Nomenclature of Vasculitides. Arthr Rheum 65:1–11 Moosig F, Bremer JP, Hellmich B, Holle JU, Holl-Ulrich K, Laudien M, Matthis C, Metzler C, No¨lle B, Richardt G, Gross WL (2013) A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg–Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis 72:1011–1017 Piram M, Maldini C, Mahr A (2012) Effect of race/ethnicity on risk, presentation and course of connective tissue diseases and primary systemic vasculitides. Curr Opin Rheumatol 24:193–200 Noth I, Strek ME, Leff AR (2003) Churg-Strauss syndrome. Lancet 361:587–594 Finsterer J (2010) Neurological manifestations of Churg–Strauss syndrome. Eur J Neurol 17:524–525 Mencacci NE, Bersano A, Cinnante CM, Ciammola A, Corti S, Meroni PL, Silani V (2011) Intracerebral haemorrhage, a possible presentation in Churg–Strauss syndrome: case report and review of the literature. J Neurol Sci 301(1–2):107–111 Maloon A, Fritz VU, Kaplan CL (1985) Neurological complications of systemic vasculitis. A report of 2 cases. S Afr Med J 68:603–605
