Letters
Table. SDAVF Acute Neurological Worsening After Steroid Administration Sex
Age, y
SDAVF Location
Söderlund et al,3 2007
Male
63
Intracranial
Methylprednisone
BP
Cabrera et al,4 2008
Male
62
L2
Methylprednisone
BP
McKeon et al,5 2011
Strowd et al,6 2012
Steroid
Male
52
Intracranial
Prednisone/methylprednisone
BP, UR
Female
51
L3
Methylprednisone
BP
Female
58
L2
Methylprednisone
BP
Male
45
L3
Prednisone/methylprednisone
BP, UR
by catheter angiography (Figure, B). The patient underwent L2 hemilaminectomy and ligation of SDAVF. At 6-month followup, he was able to walk with crutches; however, bladder function was unchanged. Magnetic resonance imaging showed marked improvement in intramedullary edema (Figure, C). Discussion | The diagnosis of SDAVF is difficult because its presenting features are similar to those seen with other neurological disorders and its radiological identification is challenging. Therefore, there is often a delay to diagnosis of SDAVF; however, disability is highly preventable when recognized and treated early.1 An SDAVF is an abnormal fistulous connection between the arterial and the venous system, which enables the flow of high-pressure spinal arterial blood into a spinal vein resulting in venous hypertension. This arterialization of the venous system compromises the normal anterograde venous drainage and results in edema, infarction, and myelopathy.2 Acute neurologic exacerbations related to SDAVF have been reported with conditions that cause increased venous hydrostatic pressure such as valsalvae, exercise, singing, and more rarely with corticosteroids (Table).5 The proposed mechanism of corticosteroid-induced exacerbation of weakness is transient fluid retention, further exacerbated when administered with a saline infusion, leading to venous engorgement and further impairment of venous egress from the dural shunt. This exacerbates spinal cord edema, resulting in neurological worsening, which may resolve as the corticosteroid-induced hypervolemia wanes. Conclusions | Transient paraplegia after receiving corticosteroids for a myelopathy associated with a conus lesion should prompt a search for SDAVF even in the absence of MRI evidence for dilated pial veins on MRI. Derek T. O’Keeffe, BM, BCh, BAO, PhD Michael A. Mikhail, MD Giuseppe Lanzino, MD David F. Kallmes, MD Brian G. Weinshenker, MD Author Affiliations: Division of Endocrinology, Mayo Clinic, Rochester, Minnesota (O’Keeffe); Department of Medicine, Mayo Clinic, Rochester, Minnesota (Mikhail); Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota (Lanzino); Department of Radiology, Mayo Clinic, Rochester, Minnesota (Kallmes); Department of Neurology, Mayo Clinic, Rochester, Minnesota (Weinshenker). Corresponding Author: Brian G. Weinshenker, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 ([email protected]). 834
Steroid-Induced Symptoms
Source
Abbreviations: BP, bilateral paraparesis; SDAVF, spinal dural arterial venous fistula; UR, urinary retention.
Conflict of Interest Disclosures: None reported. 1. Muralidharan R, Saladino A, Lanzino G, Atkinson JL, Rabinstein AA. The clinical and radiological presentation of spinal dural arteriovenous fistula. Spine (Phila Pa 1976). 2011;36(25):E1641-E1647. 2. Bernstein RA, Gress DR. Dural arteriovenous fistulas and the neurology of venous hypertension. Semin Cerebrovascular Dis Stroke. 2004;4(4):168-175. doi:10.1053/j.scds.2005.01.003. 3. Söderlund ME, Benisty S, Gaston A, Djindjian M, Cesaro P, Créange A. Can myelopathies secondary to arterio-venous dural fistulae be aggravated by intravenous corticosteroid therapy? [in French]. Rev Neurol (Paris). 2007;163 (2):235-237. 4. Cabrera M, Paradas C, Márquez C, González A. Acute paraparesis following intravenous steroid therapy in a case of dural spinal arteriovenous fistula. J Neurol. 2008;255(9):1432-1433. 5. McKeon A, Lindell EP, Atkinson JLD, Weinshenker BG, Piepgras DG, Pittock SJ. Pearls & oy-sters: clues for spinal dural arteriovenous fistulae. Neurology. 2011;76(3):e10-e12. 6. Strowd RE, Geer C, Powers A, Abou-Zeid N. A unique presentation of a spinal dural arteriovenous fistula exacerbated by steroids. J Clin Neurosci. 2012;19(3): 466-468.
COMMENT & RESPONSE
Factors Contributing to Post–Lumbar Puncture Headache To the Editor Factors associated with post–lumbar puncture headache occurrence have been thoroughly highlighted by Monserrate et al.1 The use of a smaller-tipped needle can decrease the incidence of headache (the protocol used in the study 1 ) provided that the number of punctures does not increase. Multiple punctures probably increase the incidence of headaches. If use of a smaller needle increases the number of punctures, the difference between small and large needles in producing headaches may be reduced. Therefore, the expertise of the person performing the puncture and the number of attempts are of importance; these seem to have been overlooked. Other important, yet missing, factors are pregnancy and needle bevel placement axis. The incidence of post–lumbar puncture headache increases with pregnancy, and it occurs less frequently when the needle bevel is placed parallel with the length of the neuraxis during insertion.2,3 Samad E. J. Golzari, MD Ata Mahmoodpoor, MD Reza Rikhtegar, MD Author Affiliations: Department of Anesthesiology, Tabriz University of Medical Sciences, Tabriz, Iran (Golzari, Mahmoodpoor); Department of Neurology, Tabriz University of Medical Sciences, Tabriz, Iran (Rikhtegar).
JAMA Neurology July 2015 Volume 72, Number 7 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Florida Atlantic University User on 07/18/2015
jamaneurology.com
Letters
Corresponding Author: Samad E. J. Golzari, MD, Department of Anesthesiology, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, East Azerbaijan 5137913143, Iran ([email protected]). Conflict of Interest Disclosures: None reported. 1. Monserrate AE, Ryman DC, Ma S, et al; Dominantly Inherited Alzheimer Network. Factors associated with the onset and persistence of post–lumbar puncture headache. JAMA Neurol. 2015;72(3):325-332. 2. Denny N, Masters R, Pearson D, Read J, Sihota M, Selander D. Postdural puncture headache after continuous spinal anesthesia. Anesth Analg. 1987;66 (8):791-794. 3. Mihic DN. Postspinal headaches, needle surfaces, and longitudinal orientation of the dural fibers: results of a survey [in German]. Reg Anaesth. 1986;9(2):54-56.
In Reply On behalf of the Dominantly Inherited Alzheimer Network, we thank Golzari and colleagues for their interest in our report1 and comments. We agree that the number of attempts made to obtain cerebrospinal fluid and the experience of the clinician with the specific needle type may be additional factors that could affect the incidence or severity of post–lumbar puncture headaches. We did not analyze this in our study because the number of needle insertions into the lumbar thecal space was not part of the study outcome. In our study, bevel orientation was not a significant factor because we specifically used a symmetric noncutting needle (Sprotte), which lacks a bevel. We also excluded participants who were pregnant from research lumbar puncture. Randall J. Bateman, MD John C. Morris, MD Author Affiliations: Department of Neurology, Washington University School of Medicine, St Louis, Missouri; Dominantly Inherited Alzheimer Network Clinical Core, Washington University School of Medicine, St Louis, Missouri. Corresponding Author: Randall J. Bateman, MD, Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8111, St Louis, MO 63110 ([email protected]). Conflict of Interest Disclosures: None reported. Funding/Support: This article was supported by the Washington University Institute of Clinical and Translational Sciences grants UL1 TR000448 and TL1 TR000449 from the National Center for Advancing Translational Sciences. The Dominantly Inherited Alzheimer Network is supported by National Institute on Aging grant U19 AG032438 (Dr Morris) and by the generous support of F. Simmons and O. Mohan, in addition to Dominantly Inherited Alzheimer Network site support from the German Center for Neurodegenerative Diseases, the National Institute for Health Research Queen Square Dementia Biomedical Research Unit, and J. O. and J. R. Wicking Trust grants 13026 and 20821. Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
stein and colleagues,1 demonstrating that NEDA at 2 years has potential prognostic significance, is timely. Interestingly, the authors1 found a dissociation between clinical and magnetic resonance imaging (MRI) disease activity, raising the question of whether the lack of disease progression truly reflects evidence of absence or absence of evidence. Magnetic resonance imaging disease activity as currently defined in NEDA (new or enlarged T2 bright lesions or gadolinium enhancement) may not incorporate all aspects of MS disease activity and is not sensitive to well pathologically characterized neurodegenerative features present at every disease stage, demonstrable by gray matter lesions and brain and cord atrophy by MRI and manifested clinically with progressive cognitive impairment besides Expanded Disability Status Scale score worsening.2 Much remains to be discovered on the relation between disease activity and progression. Sustained disability progression in the absence of relapses is relatively uncommon in placebo-treated patients with relapsing-remitting MS participating in clinical trials, especially when patients are required to sustain an increase in Expanded Disability Status Scale score for more than 6 months. Therefore, NEDA could be considered an intermediate outcome for gauging response to treatment relatively early in the course of MS. Further studies are required to determine what other measures NEDA should incorporate to better predict more significant long-term outcomes, including development of progressive disease (which is not sharply defined), certain disability milestones, critical degrees of global or regional atrophy, or biomarker(s) reflecting an irreversible shift from an inflammatory to a neurodegenerative process. No evidence of disease activity may also be difficult to use in the clinic because Expanded Disability Status Scale measurement and other standards are not universally used. Similarly, technical limitations of standard MRI scans in clinical practice render the practice of assessing serial T2 lesion activity as a marker of treatment effect almost useless. For these reasons, the current NEDA definition could not be applied to clinical practice effectively without increasing resources to assess patients in most practices. Although further research is needed to conclude NEDA is a surrogate measure for complete absence of disease, NEDA clearly could help with the immediate management of patients with MS and in determining when to switch treatment if technical limitations mentioned here are addressed. More importantly, a modified NEDA could allow clinicians to determine which treatment(s) optimally help with long-term management goals such as prevention of clinical progression, brain atrophy, and neurocognitive dysfunction.
1. Monserrate AE, Ryman DC, Ma S, et al; Dominantly Inherited Alzheimer Network. Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurol. 2015;72(3):325-332.
Jacob A. Sloane, MD, PhD Caterina Mainero, MD, PhD R. Philip Kinkel, MD
No Evidence of Disease Activity in Multiple Sclerosis
Author Affiliations: Multiple Sclerosis Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Sloane); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (Mainero); Multiple Sclerosis Center, University of California, San Diego (Kinkel).
To the Editor No evidence of disease activity (NEDA) is becoming an important secondary outcome measure in multiple sclerosis (MS) clinical trials. In this context, the article by Rotjamaneurology.com
(Reprinted) JAMA Neurology July 2015 Volume 72, Number 7
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Florida Atlantic University User on 07/18/2015
835
Table. SDAVF Acute Neurological Worsening After Steroid Administration Sex
Age, y
SDAVF Location
Söderlund et al,3 2007
Male
63
Intracranial
Methylprednisone
BP
Cabrera et al,4 2008
Male
62
L2
Methylprednisone
BP
McKeon et al,5 2011
Strowd et al,6 2012
Steroid
Male
52
Intracranial
Prednisone/methylprednisone
BP, UR
Female
51
L3
Methylprednisone
BP
Female
58
L2
Methylprednisone
BP
Male
45
L3
Prednisone/methylprednisone
BP, UR
by catheter angiography (Figure, B). The patient underwent L2 hemilaminectomy and ligation of SDAVF. At 6-month followup, he was able to walk with crutches; however, bladder function was unchanged. Magnetic resonance imaging showed marked improvement in intramedullary edema (Figure, C). Discussion | The diagnosis of SDAVF is difficult because its presenting features are similar to those seen with other neurological disorders and its radiological identification is challenging. Therefore, there is often a delay to diagnosis of SDAVF; however, disability is highly preventable when recognized and treated early.1 An SDAVF is an abnormal fistulous connection between the arterial and the venous system, which enables the flow of high-pressure spinal arterial blood into a spinal vein resulting in venous hypertension. This arterialization of the venous system compromises the normal anterograde venous drainage and results in edema, infarction, and myelopathy.2 Acute neurologic exacerbations related to SDAVF have been reported with conditions that cause increased venous hydrostatic pressure such as valsalvae, exercise, singing, and more rarely with corticosteroids (Table).5 The proposed mechanism of corticosteroid-induced exacerbation of weakness is transient fluid retention, further exacerbated when administered with a saline infusion, leading to venous engorgement and further impairment of venous egress from the dural shunt. This exacerbates spinal cord edema, resulting in neurological worsening, which may resolve as the corticosteroid-induced hypervolemia wanes. Conclusions | Transient paraplegia after receiving corticosteroids for a myelopathy associated with a conus lesion should prompt a search for SDAVF even in the absence of MRI evidence for dilated pial veins on MRI. Derek T. O’Keeffe, BM, BCh, BAO, PhD Michael A. Mikhail, MD Giuseppe Lanzino, MD David F. Kallmes, MD Brian G. Weinshenker, MD Author Affiliations: Division of Endocrinology, Mayo Clinic, Rochester, Minnesota (O’Keeffe); Department of Medicine, Mayo Clinic, Rochester, Minnesota (Mikhail); Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota (Lanzino); Department of Radiology, Mayo Clinic, Rochester, Minnesota (Kallmes); Department of Neurology, Mayo Clinic, Rochester, Minnesota (Weinshenker). Corresponding Author: Brian G. Weinshenker, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 ([email protected]). 834
Steroid-Induced Symptoms
Source
Abbreviations: BP, bilateral paraparesis; SDAVF, spinal dural arterial venous fistula; UR, urinary retention.
Conflict of Interest Disclosures: None reported. 1. Muralidharan R, Saladino A, Lanzino G, Atkinson JL, Rabinstein AA. The clinical and radiological presentation of spinal dural arteriovenous fistula. Spine (Phila Pa 1976). 2011;36(25):E1641-E1647. 2. Bernstein RA, Gress DR. Dural arteriovenous fistulas and the neurology of venous hypertension. Semin Cerebrovascular Dis Stroke. 2004;4(4):168-175. doi:10.1053/j.scds.2005.01.003. 3. Söderlund ME, Benisty S, Gaston A, Djindjian M, Cesaro P, Créange A. Can myelopathies secondary to arterio-venous dural fistulae be aggravated by intravenous corticosteroid therapy? [in French]. Rev Neurol (Paris). 2007;163 (2):235-237. 4. Cabrera M, Paradas C, Márquez C, González A. Acute paraparesis following intravenous steroid therapy in a case of dural spinal arteriovenous fistula. J Neurol. 2008;255(9):1432-1433. 5. McKeon A, Lindell EP, Atkinson JLD, Weinshenker BG, Piepgras DG, Pittock SJ. Pearls & oy-sters: clues for spinal dural arteriovenous fistulae. Neurology. 2011;76(3):e10-e12. 6. Strowd RE, Geer C, Powers A, Abou-Zeid N. A unique presentation of a spinal dural arteriovenous fistula exacerbated by steroids. J Clin Neurosci. 2012;19(3): 466-468.
COMMENT & RESPONSE
Factors Contributing to Post–Lumbar Puncture Headache To the Editor Factors associated with post–lumbar puncture headache occurrence have been thoroughly highlighted by Monserrate et al.1 The use of a smaller-tipped needle can decrease the incidence of headache (the protocol used in the study 1 ) provided that the number of punctures does not increase. Multiple punctures probably increase the incidence of headaches. If use of a smaller needle increases the number of punctures, the difference between small and large needles in producing headaches may be reduced. Therefore, the expertise of the person performing the puncture and the number of attempts are of importance; these seem to have been overlooked. Other important, yet missing, factors are pregnancy and needle bevel placement axis. The incidence of post–lumbar puncture headache increases with pregnancy, and it occurs less frequently when the needle bevel is placed parallel with the length of the neuraxis during insertion.2,3 Samad E. J. Golzari, MD Ata Mahmoodpoor, MD Reza Rikhtegar, MD Author Affiliations: Department of Anesthesiology, Tabriz University of Medical Sciences, Tabriz, Iran (Golzari, Mahmoodpoor); Department of Neurology, Tabriz University of Medical Sciences, Tabriz, Iran (Rikhtegar).
JAMA Neurology July 2015 Volume 72, Number 7 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Florida Atlantic University User on 07/18/2015
jamaneurology.com
Letters
Corresponding Author: Samad E. J. Golzari, MD, Department of Anesthesiology, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, East Azerbaijan 5137913143, Iran ([email protected]). Conflict of Interest Disclosures: None reported. 1. Monserrate AE, Ryman DC, Ma S, et al; Dominantly Inherited Alzheimer Network. Factors associated with the onset and persistence of post–lumbar puncture headache. JAMA Neurol. 2015;72(3):325-332. 2. Denny N, Masters R, Pearson D, Read J, Sihota M, Selander D. Postdural puncture headache after continuous spinal anesthesia. Anesth Analg. 1987;66 (8):791-794. 3. Mihic DN. Postspinal headaches, needle surfaces, and longitudinal orientation of the dural fibers: results of a survey [in German]. Reg Anaesth. 1986;9(2):54-56.
In Reply On behalf of the Dominantly Inherited Alzheimer Network, we thank Golzari and colleagues for their interest in our report1 and comments. We agree that the number of attempts made to obtain cerebrospinal fluid and the experience of the clinician with the specific needle type may be additional factors that could affect the incidence or severity of post–lumbar puncture headaches. We did not analyze this in our study because the number of needle insertions into the lumbar thecal space was not part of the study outcome. In our study, bevel orientation was not a significant factor because we specifically used a symmetric noncutting needle (Sprotte), which lacks a bevel. We also excluded participants who were pregnant from research lumbar puncture. Randall J. Bateman, MD John C. Morris, MD Author Affiliations: Department of Neurology, Washington University School of Medicine, St Louis, Missouri; Dominantly Inherited Alzheimer Network Clinical Core, Washington University School of Medicine, St Louis, Missouri. Corresponding Author: Randall J. Bateman, MD, Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8111, St Louis, MO 63110 ([email protected]). Conflict of Interest Disclosures: None reported. Funding/Support: This article was supported by the Washington University Institute of Clinical and Translational Sciences grants UL1 TR000448 and TL1 TR000449 from the National Center for Advancing Translational Sciences. The Dominantly Inherited Alzheimer Network is supported by National Institute on Aging grant U19 AG032438 (Dr Morris) and by the generous support of F. Simmons and O. Mohan, in addition to Dominantly Inherited Alzheimer Network site support from the German Center for Neurodegenerative Diseases, the National Institute for Health Research Queen Square Dementia Biomedical Research Unit, and J. O. and J. R. Wicking Trust grants 13026 and 20821. Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript, and the decision to submit the manuscript for publication. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
stein and colleagues,1 demonstrating that NEDA at 2 years has potential prognostic significance, is timely. Interestingly, the authors1 found a dissociation between clinical and magnetic resonance imaging (MRI) disease activity, raising the question of whether the lack of disease progression truly reflects evidence of absence or absence of evidence. Magnetic resonance imaging disease activity as currently defined in NEDA (new or enlarged T2 bright lesions or gadolinium enhancement) may not incorporate all aspects of MS disease activity and is not sensitive to well pathologically characterized neurodegenerative features present at every disease stage, demonstrable by gray matter lesions and brain and cord atrophy by MRI and manifested clinically with progressive cognitive impairment besides Expanded Disability Status Scale score worsening.2 Much remains to be discovered on the relation between disease activity and progression. Sustained disability progression in the absence of relapses is relatively uncommon in placebo-treated patients with relapsing-remitting MS participating in clinical trials, especially when patients are required to sustain an increase in Expanded Disability Status Scale score for more than 6 months. Therefore, NEDA could be considered an intermediate outcome for gauging response to treatment relatively early in the course of MS. Further studies are required to determine what other measures NEDA should incorporate to better predict more significant long-term outcomes, including development of progressive disease (which is not sharply defined), certain disability milestones, critical degrees of global or regional atrophy, or biomarker(s) reflecting an irreversible shift from an inflammatory to a neurodegenerative process. No evidence of disease activity may also be difficult to use in the clinic because Expanded Disability Status Scale measurement and other standards are not universally used. Similarly, technical limitations of standard MRI scans in clinical practice render the practice of assessing serial T2 lesion activity as a marker of treatment effect almost useless. For these reasons, the current NEDA definition could not be applied to clinical practice effectively without increasing resources to assess patients in most practices. Although further research is needed to conclude NEDA is a surrogate measure for complete absence of disease, NEDA clearly could help with the immediate management of patients with MS and in determining when to switch treatment if technical limitations mentioned here are addressed. More importantly, a modified NEDA could allow clinicians to determine which treatment(s) optimally help with long-term management goals such as prevention of clinical progression, brain atrophy, and neurocognitive dysfunction.
1. Monserrate AE, Ryman DC, Ma S, et al; Dominantly Inherited Alzheimer Network. Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurol. 2015;72(3):325-332.
Jacob A. Sloane, MD, PhD Caterina Mainero, MD, PhD R. Philip Kinkel, MD
No Evidence of Disease Activity in Multiple Sclerosis
Author Affiliations: Multiple Sclerosis Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Sloane); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (Mainero); Multiple Sclerosis Center, University of California, San Diego (Kinkel).
To the Editor No evidence of disease activity (NEDA) is becoming an important secondary outcome measure in multiple sclerosis (MS) clinical trials. In this context, the article by Rotjamaneurology.com
(Reprinted) JAMA Neurology July 2015 Volume 72, Number 7
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Florida Atlantic University User on 07/18/2015
835
