- Email: [email protected]
Psychosis in children with systemic lupus erythematosus: the role of steroids as both treatment and cause
Psychosis in Children with Systemic Lupus Erythematosus: The Role of Steroids as Both Treatment and Cause Orna Alpert, Raman Marwaha, Hsiang Huang PII: DOI: Reference:
S0163-8343(14)00107-8 doi: 10.1016/j.genhosppsych.2014.05.001 GHP 6852
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
25 March 2014 23 April 2014 1 May 2014
Please cite this article as: Alpert Orna, Marwaha Raman, Huang Hsiang, Psychosis in Children with Systemic Lupus Erythematosus: The Role of Steroids as Both Treatment and Cause, General Hospital Psychiatry (2014), doi: 10.1016/j.genhosppsych.2014.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Psychosis in Children with Systemic Lupus Erythematosus: The Role of Steroids
T
as Both Treatment and Cause
RI P
Authors: Orna Alpert1, Raman Marwaha1, Hsiang Huang2 1. Department of Child and Adolescent Psychiatry, Children’s Hospital of
SC
Philadelphia, Philadelphia, PA
NU
2. Department of Psychiatry, Cambridge Health Alliance, Harvard Medical
MA
School, Cambridge, MA
Corresponding author:
ED
Orna Alpert, MD
PT
Address:
CE
3501 Civic Center Blvd, Philadelphia, PA 19104 Email: [email protected]
AC
Phone: 732 331 4391
Conflict of Interest Notification: Drs. Alpert, Marwaha, and Huang have no conflicts of interest to disclose.
ACCEPTED MANUSCRIPT
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ABSTRACT
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RI P
Steroids may both be a cause of and treatment for pediatric patients with Systemic Lupus Erythematosus (SLE) presenting with psychotic symptoms. We present two cases demonstrating that careful histories (including prior steroid exposure) and the use of biomarkers can help guide the management of children with SLE presenting with psychosis.
NU
Introduction
PT
Case descriptions
ED
MA
Neuropsychiatric lupus refers to psychiatric-neurologic manifestations that develop secondary to CNS involvement in patients with systemic lupus erythematosus (SLE). It is a diagnosis of exclusion which can be made after infection, electrolyte abnormalities, drug side effects, mass lesion, renal failure, and primary psychiatric disorders have been ruled out (1). We describe two pediatric SLE cases presenting with psychosis to illustrate the difficulty encountered when trying to determine whether psychotic symptoms observed are a result of primary neuropsychiatric SLE or steroid exposure.
AC
CE
Patient J is a 14 year old female without significant medical history who presented with acute onset of altered mental status, generalized weakness, and abdominal pain. On examination, she was moaning, disoriented, had nonpurposeful movements, and experienced auditory and visual hallucinations. She was well until 2 days prior to admission when she complained of left sided chest pain and mild cough. In the Emergency Department, she developed a generalized tonic-clonic seizure. Initial tests showed: pericardial effusion on echocardiogram, enlargement of the third and lateral ventricles and cerebral sulci on head CT, elevated LDH, and pancytopenia. Further laboratory work up was positive for Ribosomal P antibody (150 AU/ml), anti-nuclear antibody with ANA titer 1:1280, anti-neutrophil cyto antibody, DNA Binding, anti-SM antibody, antiSS-A antibody and anti-RNP antibody. She was admitted to the pediatric ICU and intubated due to respiratory failure (dexmedetomidine was used for sedation). Evaluation by the rheumatology service revealed 5 criteria for SLE: serositis, pancytopenia, malar rash, CNS disease, and proteinuria. She received methylprednisolone, cyclophosphamide, rituximab and underwent plasmapheresis. She was extubated and after 3-4 days her mental status returned to baseline. Clonidine 0.2 mg at bed time was used to adjust her sleepwake cycle. Patient T is a 17 year old female with history of SLE and stage IV lupus
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NU
SC
RI P
T
nephritis brought in by police after taking her father’s car, crashing it, and subsequently walking around the streets in an agitated and incoherent state. On admission, she was found to be delirious and psychotic. She had no fevers, rash, cough, joint pain or mouth sores. On history, it was discovered that she had been treated with pulse methylprednisolone, prednisone and cyclophosphamide 2-3 weeks prior to admission. Her brain MRI and EEG were normal. Her vital signs showed autonomic instability and IV access was started in the event that intravenous medications became necessary. Her initial laboratory work up included positive ANA with ANA titer:> OR=1:1280, positive Anti-Neutrophil Cytoplasmic antibody, positive anti- Cardiolipin IGG (32 GPL) and IGM (18MPL) and elevated CRP (1.2 mg/L) and ESR (40 mm hr). Anti-NMDA receptor antibodies and Ribosomal P antibody were negative. She was treated with oral haloperidol 10 mg twice daily. Prednisone 60mg was tapered over 14 days while she received weekly cyclophosphamide (2-3 doses) and Rituximab. The patient responded well to treatment with resolution of symptoms and returned to baseline before discharge.
Discussion
AC
CE
PT
ED
Neuropsychiatric syndromes in SLE as defined by the American College of Rheumatology nomenclature can present as headache, cerebrovascular disease, seizure disorder, delirium, cognitive dysfunction, depression, anxiety disorder. Most common is headache with a prevalence of 72% followed by mood disorder (57%), cognitive disorder (55%) and psychosis (12%) (2). Children who develop neuropsychiatric lupus in the context of SLE tend to present with psychosis more frequently than adults (3). Neurological involvement appears to be more severe in children who may accrue permanent organ damage at higher rates than adults (4). In a prospective study of NPSLE in children, nervous system manifestations were more common over a 6-year study period than glomerulonephritis (95% vs 55%) (2), while a study comparing pediatric and adult SLE patients found that pediatric patients had more frequent renal disease and encephalopathy than adults (5). The pathogenesis of neuropsychiatric lupus is still unknown, although there are several mechanisms proposed including increased permeability of blood brain barrier and pro-inflammatory cytokine mediated disruption of global function (6). In studies that looked at paraneoplastic syndromes such as anti-NMDA receptor encephalitis, it is apparent that there is a role of autoantibodies in the pathogenesis of various neuropsychiatric syndromes. In steroid psychosis, the mechanism involves neuronal cell death in the amygdala, alteration in cortical dendritic spines, and changes in the level of nerve growth factor expression in septal nuclei (7). Diagnosis of neuropsychiatric lupus includes various investigations including CSF studies, autoantibodies, and neuroimaging. Many studies have
ACCEPTED MANUSCRIPT
RI P
T
shown a close correlation between neuropsychiatric lupus and presence of antiribosomal P, anti-neuronal, or anti-phospholipid antibodies (8-10). Patient J had positive Ribosomal P antibody, while Patient T’s serology was positive for antiphospholipids antibodies, both of which were indicative of neuropsychiatric lupus. Biomarkers, like autoantibodies, can help to differentiate CNS lupus from other disease processes such as TTP, vasculitis or steroid induced psychosis. Both of our cases highlight the importance of biomarkers in the diagnosis of neuropsychiatric lupus in order to differentiate one disease process from the other.
ED
MA
NU
SC
The two cases were quite challenging to diagnose and treat. Patient J’s case was clearer since her delirium was the initial presentation of her SLE. Other medical causes such as thrombotic thrombocytopenic purpura (TTP) were ruled out and the markers for neuropsychiatric lupus were positive. In contrast, patient T’s case was marked by psychotic symptoms during pulse steroid therapy for lupus nephritis. It was initially unclear if the symptoms observed were induced by steroid therapy or were a manifestation of the underlying neuropsychiatric lupus superimposed on steroid induced delirium/psychosis. Although the treatment was similar in both cases as both received cyclophosphamide and rituximab, steroids were tapered in Patient T’s case and delirium was treated with haloperidol.
AC
CE
PT
The incidence of steroid induced severe psychiatric symptoms in adults is about 6 % and females may have a slightly higher risk. Steroid psychosis can occur with all forms of administration and can present with delirium, confusion, insomnia, emotional lability, and manic/ depressive symptoms. Long- term steroid treatment can lead to disturbance of memory, attention and occupational performance. Symptoms usually resolve within 3-11 months after discontinuation, however it is not uncommon to see persistent psychosis after the taper has been completed (7). Multiple steroid preparations are available for use in pediatric patients. Among IV preparations, dexamethasone and methylprednisolone are commonly used especially in oncology, rheumatology (e.g. encephalitis), pulmonology, and solid organ transplantation. Despite its wide use in pediatric populations, steroidinduced psychosis occurs rarely in children. The duration for tapering of steroids depends on the condition being treated, the dose and duration of use, and other medical considerations. It has been suggested that atypical antipsychotics such as olanzapine, risperidone and quetiapine could be used in children as they are associated with less extrapyramidal compared with typical antipsychotics (7). For Patient T, we used haloperidol for symptom control since it could be administered parenterally in the event that her respiratory status was to worsen.
No specific guidelines exist for management of CNS lupus, although common treatments include cyclophosphamide, methylprednisolone, prednisone,
ACCEPTED MANUSCRIPT
RI P
T
rituximab, and plasmapheresis. Haloperidol for the management of delirium and clonidine and melatonin have been used to regulate the sleep/awake cycle. Research has shown the efficacy of methylprednisolone in reducing symptoms of lupus and usually it is the first medication administered, however cyclophosphamide is considered more effective in reducing symptoms of neuropsychiatric involvement in lupus compared to methylprednisolone. Use of methylprednisolone in the treatment of CNS lupus highlights the importance of differentiating between lupus psychosis and steroid induced psychosis.
NU
SC
Neuropsychiatric Systemic Lupus Erythematosus is a diagnostic and therapeutic challenge. Our cases highlight the importance of biomarkers like autoantibodies in helping to make the diagnosis of neuropsychiatric lupus and collecting a history of steroid exposure to rule in/out steroid induced psychosis. Guidelines for the clinician regarding diagnosis and treatment of neuropsychiatric manifestations of Systemic Lupus Erythematosus are needed.
MA
Disclosures
ED
The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. References
AC
CE
PT
1. Miguel EC, Pereira RM, Pereira CA, Baer L, Gomes RE, de Sa LC, et al. Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients. Medicine (Baltimore). 1994 Jul;73(4):224-32. 2. Sibbitt WL, Jr., Brandt JR, Johnson CR, Maldonado ME, Patel SR, Ford CC, et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol. 2002 Jul;29(7):1536-42. 3. Brunner HI, Gladman DD, Ibanez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008 Feb;58(2):556-62. 4. Tucker LB, Uribe AG, Fernandez M, Vila LM, McGwin G, Apte M, et al. Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus. 2008 Apr;17(4):314-22. 5. Hoffman IE, Lauwerys BR, De Keyser F, Huizinga TW, Isenberg D, Cebecauer L, et al. Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis. 2009 Mar;68(3):412-5. 6. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol. 2010 Jun;6(6):358-67. 7. Ross DA, Cetas JS. Steroid psychosis: a review for neurosurgeons. J Neurooncol. 2012 Sep;109(3):439-47.
ACCEPTED MANUSCRIPT
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CE
PT
ED
MA
NU
SC
RI P
T
8. Abdel-Nasser AM, Ghaleb RM, Mahmoud JA, Khairy W, Mahmoud RM. Association of anti-ribosomal P protein antibodies with neuropsychiatric and other manifestations of systemic lupus erythematosus. Clin Rheumatol. 2008 Nov;27(11):1377-85. 9. Afeltra A, Garzia P, Mitterhofer AP, Vadacca M, Galluzzo S, Del Porto F, et al. Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies. Neurology. 2003 Jul 8;61(1):108-10. 10. Sanna G, Bertolaccini ML, Cuadrado MJ, Laing H, Khamashta MA, Mathieu A, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003 May;30(5):985-92.
S0163-8343(14)00107-8 doi: 10.1016/j.genhosppsych.2014.05.001 GHP 6852
To appear in:
General Hospital Psychiatry
Received date: Revised date: Accepted date:
25 March 2014 23 April 2014 1 May 2014
Please cite this article as: Alpert Orna, Marwaha Raman, Huang Hsiang, Psychosis in Children with Systemic Lupus Erythematosus: The Role of Steroids as Both Treatment and Cause, General Hospital Psychiatry (2014), doi: 10.1016/j.genhosppsych.2014.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Psychosis in Children with Systemic Lupus Erythematosus: The Role of Steroids
T
as Both Treatment and Cause
RI P
Authors: Orna Alpert1, Raman Marwaha1, Hsiang Huang2 1. Department of Child and Adolescent Psychiatry, Children’s Hospital of
SC
Philadelphia, Philadelphia, PA
NU
2. Department of Psychiatry, Cambridge Health Alliance, Harvard Medical
MA
School, Cambridge, MA
Corresponding author:
ED
Orna Alpert, MD
PT
Address:
CE
3501 Civic Center Blvd, Philadelphia, PA 19104 Email: [email protected]
AC
Phone: 732 331 4391
Conflict of Interest Notification: Drs. Alpert, Marwaha, and Huang have no conflicts of interest to disclose.
ACCEPTED MANUSCRIPT
T
ABSTRACT
SC
RI P
Steroids may both be a cause of and treatment for pediatric patients with Systemic Lupus Erythematosus (SLE) presenting with psychotic symptoms. We present two cases demonstrating that careful histories (including prior steroid exposure) and the use of biomarkers can help guide the management of children with SLE presenting with psychosis.
NU
Introduction
PT
Case descriptions
ED
MA
Neuropsychiatric lupus refers to psychiatric-neurologic manifestations that develop secondary to CNS involvement in patients with systemic lupus erythematosus (SLE). It is a diagnosis of exclusion which can be made after infection, electrolyte abnormalities, drug side effects, mass lesion, renal failure, and primary psychiatric disorders have been ruled out (1). We describe two pediatric SLE cases presenting with psychosis to illustrate the difficulty encountered when trying to determine whether psychotic symptoms observed are a result of primary neuropsychiatric SLE or steroid exposure.
AC
CE
Patient J is a 14 year old female without significant medical history who presented with acute onset of altered mental status, generalized weakness, and abdominal pain. On examination, she was moaning, disoriented, had nonpurposeful movements, and experienced auditory and visual hallucinations. She was well until 2 days prior to admission when she complained of left sided chest pain and mild cough. In the Emergency Department, she developed a generalized tonic-clonic seizure. Initial tests showed: pericardial effusion on echocardiogram, enlargement of the third and lateral ventricles and cerebral sulci on head CT, elevated LDH, and pancytopenia. Further laboratory work up was positive for Ribosomal P antibody (150 AU/ml), anti-nuclear antibody with ANA titer 1:1280, anti-neutrophil cyto antibody, DNA Binding, anti-SM antibody, antiSS-A antibody and anti-RNP antibody. She was admitted to the pediatric ICU and intubated due to respiratory failure (dexmedetomidine was used for sedation). Evaluation by the rheumatology service revealed 5 criteria for SLE: serositis, pancytopenia, malar rash, CNS disease, and proteinuria. She received methylprednisolone, cyclophosphamide, rituximab and underwent plasmapheresis. She was extubated and after 3-4 days her mental status returned to baseline. Clonidine 0.2 mg at bed time was used to adjust her sleepwake cycle. Patient T is a 17 year old female with history of SLE and stage IV lupus
ACCEPTED MANUSCRIPT
MA
NU
SC
RI P
T
nephritis brought in by police after taking her father’s car, crashing it, and subsequently walking around the streets in an agitated and incoherent state. On admission, she was found to be delirious and psychotic. She had no fevers, rash, cough, joint pain or mouth sores. On history, it was discovered that she had been treated with pulse methylprednisolone, prednisone and cyclophosphamide 2-3 weeks prior to admission. Her brain MRI and EEG were normal. Her vital signs showed autonomic instability and IV access was started in the event that intravenous medications became necessary. Her initial laboratory work up included positive ANA with ANA titer:> OR=1:1280, positive Anti-Neutrophil Cytoplasmic antibody, positive anti- Cardiolipin IGG (32 GPL) and IGM (18MPL) and elevated CRP (1.2 mg/L) and ESR (40 mm hr). Anti-NMDA receptor antibodies and Ribosomal P antibody were negative. She was treated with oral haloperidol 10 mg twice daily. Prednisone 60mg was tapered over 14 days while she received weekly cyclophosphamide (2-3 doses) and Rituximab. The patient responded well to treatment with resolution of symptoms and returned to baseline before discharge.
Discussion
AC
CE
PT
ED
Neuropsychiatric syndromes in SLE as defined by the American College of Rheumatology nomenclature can present as headache, cerebrovascular disease, seizure disorder, delirium, cognitive dysfunction, depression, anxiety disorder. Most common is headache with a prevalence of 72% followed by mood disorder (57%), cognitive disorder (55%) and psychosis (12%) (2). Children who develop neuropsychiatric lupus in the context of SLE tend to present with psychosis more frequently than adults (3). Neurological involvement appears to be more severe in children who may accrue permanent organ damage at higher rates than adults (4). In a prospective study of NPSLE in children, nervous system manifestations were more common over a 6-year study period than glomerulonephritis (95% vs 55%) (2), while a study comparing pediatric and adult SLE patients found that pediatric patients had more frequent renal disease and encephalopathy than adults (5). The pathogenesis of neuropsychiatric lupus is still unknown, although there are several mechanisms proposed including increased permeability of blood brain barrier and pro-inflammatory cytokine mediated disruption of global function (6). In studies that looked at paraneoplastic syndromes such as anti-NMDA receptor encephalitis, it is apparent that there is a role of autoantibodies in the pathogenesis of various neuropsychiatric syndromes. In steroid psychosis, the mechanism involves neuronal cell death in the amygdala, alteration in cortical dendritic spines, and changes in the level of nerve growth factor expression in septal nuclei (7). Diagnosis of neuropsychiatric lupus includes various investigations including CSF studies, autoantibodies, and neuroimaging. Many studies have
ACCEPTED MANUSCRIPT
RI P
T
shown a close correlation between neuropsychiatric lupus and presence of antiribosomal P, anti-neuronal, or anti-phospholipid antibodies (8-10). Patient J had positive Ribosomal P antibody, while Patient T’s serology was positive for antiphospholipids antibodies, both of which were indicative of neuropsychiatric lupus. Biomarkers, like autoantibodies, can help to differentiate CNS lupus from other disease processes such as TTP, vasculitis or steroid induced psychosis. Both of our cases highlight the importance of biomarkers in the diagnosis of neuropsychiatric lupus in order to differentiate one disease process from the other.
ED
MA
NU
SC
The two cases were quite challenging to diagnose and treat. Patient J’s case was clearer since her delirium was the initial presentation of her SLE. Other medical causes such as thrombotic thrombocytopenic purpura (TTP) were ruled out and the markers for neuropsychiatric lupus were positive. In contrast, patient T’s case was marked by psychotic symptoms during pulse steroid therapy for lupus nephritis. It was initially unclear if the symptoms observed were induced by steroid therapy or were a manifestation of the underlying neuropsychiatric lupus superimposed on steroid induced delirium/psychosis. Although the treatment was similar in both cases as both received cyclophosphamide and rituximab, steroids were tapered in Patient T’s case and delirium was treated with haloperidol.
AC
CE
PT
The incidence of steroid induced severe psychiatric symptoms in adults is about 6 % and females may have a slightly higher risk. Steroid psychosis can occur with all forms of administration and can present with delirium, confusion, insomnia, emotional lability, and manic/ depressive symptoms. Long- term steroid treatment can lead to disturbance of memory, attention and occupational performance. Symptoms usually resolve within 3-11 months after discontinuation, however it is not uncommon to see persistent psychosis after the taper has been completed (7). Multiple steroid preparations are available for use in pediatric patients. Among IV preparations, dexamethasone and methylprednisolone are commonly used especially in oncology, rheumatology (e.g. encephalitis), pulmonology, and solid organ transplantation. Despite its wide use in pediatric populations, steroidinduced psychosis occurs rarely in children. The duration for tapering of steroids depends on the condition being treated, the dose and duration of use, and other medical considerations. It has been suggested that atypical antipsychotics such as olanzapine, risperidone and quetiapine could be used in children as they are associated with less extrapyramidal compared with typical antipsychotics (7). For Patient T, we used haloperidol for symptom control since it could be administered parenterally in the event that her respiratory status was to worsen.
No specific guidelines exist for management of CNS lupus, although common treatments include cyclophosphamide, methylprednisolone, prednisone,
ACCEPTED MANUSCRIPT
RI P
T
rituximab, and plasmapheresis. Haloperidol for the management of delirium and clonidine and melatonin have been used to regulate the sleep/awake cycle. Research has shown the efficacy of methylprednisolone in reducing symptoms of lupus and usually it is the first medication administered, however cyclophosphamide is considered more effective in reducing symptoms of neuropsychiatric involvement in lupus compared to methylprednisolone. Use of methylprednisolone in the treatment of CNS lupus highlights the importance of differentiating between lupus psychosis and steroid induced psychosis.
NU
SC
Neuropsychiatric Systemic Lupus Erythematosus is a diagnostic and therapeutic challenge. Our cases highlight the importance of biomarkers like autoantibodies in helping to make the diagnosis of neuropsychiatric lupus and collecting a history of steroid exposure to rule in/out steroid induced psychosis. Guidelines for the clinician regarding diagnosis and treatment of neuropsychiatric manifestations of Systemic Lupus Erythematosus are needed.
MA
Disclosures
ED
The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. References
AC
CE
PT
1. Miguel EC, Pereira RM, Pereira CA, Baer L, Gomes RE, de Sa LC, et al. Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients. Medicine (Baltimore). 1994 Jul;73(4):224-32. 2. Sibbitt WL, Jr., Brandt JR, Johnson CR, Maldonado ME, Patel SR, Ford CC, et al. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus. J Rheumatol. 2002 Jul;29(7):1536-42. 3. Brunner HI, Gladman DD, Ibanez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008 Feb;58(2):556-62. 4. Tucker LB, Uribe AG, Fernandez M, Vila LM, McGwin G, Apte M, et al. Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus. 2008 Apr;17(4):314-22. 5. Hoffman IE, Lauwerys BR, De Keyser F, Huizinga TW, Isenberg D, Cebecauer L, et al. Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis. 2009 Mar;68(3):412-5. 6. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol. 2010 Jun;6(6):358-67. 7. Ross DA, Cetas JS. Steroid psychosis: a review for neurosurgeons. J Neurooncol. 2012 Sep;109(3):439-47.
ACCEPTED MANUSCRIPT
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CE
PT
ED
MA
NU
SC
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T
8. Abdel-Nasser AM, Ghaleb RM, Mahmoud JA, Khairy W, Mahmoud RM. Association of anti-ribosomal P protein antibodies with neuropsychiatric and other manifestations of systemic lupus erythematosus. Clin Rheumatol. 2008 Nov;27(11):1377-85. 9. Afeltra A, Garzia P, Mitterhofer AP, Vadacca M, Galluzzo S, Del Porto F, et al. Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies. Neurology. 2003 Jul 8;61(1):108-10. 10. Sanna G, Bertolaccini ML, Cuadrado MJ, Laing H, Khamashta MA, Mathieu A, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003 May;30(5):985-92.