Section Editor
®
WriteClick Editor’s Choice
Robert C. Griggs, MD
Editors’ Note: Gilbert inquires whether Alperin et al., who studied the role of low-dose acetazolamide in normalpressure hydrocephalus, evaluated the change in CSF pressure while the patients were being treated. Alperin et al. respond. Commenting on “Risk factors for EEG seizures in neonates treated with hypothermia,” Rothman raises some interesting questions. Glass et al., authors of the study, respond and direct some of the questions to the neurology and neonatology community. —Chafic Karam, MD, and Robert C. Griggs, MD
LOW-DOSE ACETAZOLAMIDE REVERSES PERIVENTRICULAR WHITE MATTER HYPERINTENSITIES IN iNPH
Gordon J. Gilbert, St. Petersburg, FL: Alperin et al.1 highlighted the efficacy of acetazolamide in the treatment of normal-pressure hydrocephalus (NPH) and included information about the CSF volumes but not pressures. In the original report on NPH and the mechanism of ventricular dilation,2 the formula F 5 PA was considered because the force exerted against the ventricular walls is increased in the presence of increased ventricular wall area so that a normal CSF pressure can exert a higher dilating force. Did the authors evaluate the change in CSF pressure resulting from even low doses of acetazolamide? This would be useful in evaluating its apparent efficacy in the 5 patients who responded with improved gait and reduced periventricular hyperintensities. In addition, it would explain the 3 who had no response and may not have had a reduction in CSF pressure. The authors’ findings may prompt a trial on medical therapy for NPH with surgical referral only for nonresponders. Author Response: Noam Alperin, Carlos Olio, Miami; Norm Relkin, New York: We thank Dr. Gilbert for his important question related to our article.1 Evaluation of changes in intracranial pressure (ICP) following treatment is critical in understanding the idiopathic NPH (iNPH) disease process and could provide insight about whether response to acetazolamide requires a reduction in ICP. Ishikawa et al.3 reported that opening CSF pressures greater than 11 mm Hg (15 cm H2O) improved
sensitivity for predicting shunt responsiveness. This supports the notion that reversal of the impaired CSF homeostasis in iNPH does not require a large reduction in ICP. Measuring ICP may also permit optimal titration of acetazolamide dose, since excessive reductions in pressure can potentially hamper CSF clearance. The current study was conducted within the limits imposed by offlabel clinical use of acetazolamide. Therefore, invasive CSF pressure readings were not performed during treatment. A prospective trial that incorporates noninvasive assessment of ICP, prior to and following each dose escalation, is being developed. The CSF pressure will be assessed using an MRI-based technique (magnetic resonance ICP [MRICP]).4 Previous successful applications in general hydrocephalous5 and more recently in shunted hydrocephalic patients6 justify the inclusion of MRICP scans in future studies of pharmacotherapy for iNPH. © 2014 American Academy of Neurology 1.
2.
3.
4.
5.
6.
Alperin N, Oliu CJ, Bagci AM, et al. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology 2014;82:1347–1351. Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure: observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 1965;2:307–327. Ishikawa M, Hashimoto M, Mori E, et al. The value of the cerebrospinal fluid tap test for predicting shunt effectiveness in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 2012;9:1. Alperin NJ, Lee SH, Loth F, Raksin PB, Lichtor T. MR intracranial pressure (ICP): a method to measure intracranial elastance and pressure noninvasively by means of MR imaging: baboon and human study. Radiology 2000;217:877–885. Glick RP, Niebruegge J, Lee SH, et al. Early experience from the application of a noninvasive magnetic resonance imaging-based measurement of intracranial pressure in hydrocephalus. Neurosurgery 2006;59:1052–1060. Muehlmann M, Koerte IK, Laubender RP, et al. Magnetic resonance-based estimation of intracranial pressure correlates with ventriculoperitoneal shunt valve opening pressure setting in children with hydrocephalus. Invest Radiol 2013;48:543–547.
RISK FACTORS FOR EEG SEIZURES IN NEONATES TREATED WITH HYPOTHERMIA: A MULTICENTER COHORT STUDY
Steven M. Rothman, St. Louis: I was fascinated by the report by Glass et al.1 on EEG seizures in almost Neurology 83
November 4, 2014
1773
Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH Gordon J. Gilbert, Noam Alperin, Carlos Olio, et al. Neurology 2014;83;1773 DOI 10.1212/WNL.0000000000000994 This information is current as of November 3, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/19/1773.1.full.html
References
This article cites 6 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/19/1773.1.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
®
WriteClick Editor’s Choice
Robert C. Griggs, MD
Editors’ Note: Gilbert inquires whether Alperin et al., who studied the role of low-dose acetazolamide in normalpressure hydrocephalus, evaluated the change in CSF pressure while the patients were being treated. Alperin et al. respond. Commenting on “Risk factors for EEG seizures in neonates treated with hypothermia,” Rothman raises some interesting questions. Glass et al., authors of the study, respond and direct some of the questions to the neurology and neonatology community. —Chafic Karam, MD, and Robert C. Griggs, MD
LOW-DOSE ACETAZOLAMIDE REVERSES PERIVENTRICULAR WHITE MATTER HYPERINTENSITIES IN iNPH
Gordon J. Gilbert, St. Petersburg, FL: Alperin et al.1 highlighted the efficacy of acetazolamide in the treatment of normal-pressure hydrocephalus (NPH) and included information about the CSF volumes but not pressures. In the original report on NPH and the mechanism of ventricular dilation,2 the formula F 5 PA was considered because the force exerted against the ventricular walls is increased in the presence of increased ventricular wall area so that a normal CSF pressure can exert a higher dilating force. Did the authors evaluate the change in CSF pressure resulting from even low doses of acetazolamide? This would be useful in evaluating its apparent efficacy in the 5 patients who responded with improved gait and reduced periventricular hyperintensities. In addition, it would explain the 3 who had no response and may not have had a reduction in CSF pressure. The authors’ findings may prompt a trial on medical therapy for NPH with surgical referral only for nonresponders. Author Response: Noam Alperin, Carlos Olio, Miami; Norm Relkin, New York: We thank Dr. Gilbert for his important question related to our article.1 Evaluation of changes in intracranial pressure (ICP) following treatment is critical in understanding the idiopathic NPH (iNPH) disease process and could provide insight about whether response to acetazolamide requires a reduction in ICP. Ishikawa et al.3 reported that opening CSF pressures greater than 11 mm Hg (15 cm H2O) improved
sensitivity for predicting shunt responsiveness. This supports the notion that reversal of the impaired CSF homeostasis in iNPH does not require a large reduction in ICP. Measuring ICP may also permit optimal titration of acetazolamide dose, since excessive reductions in pressure can potentially hamper CSF clearance. The current study was conducted within the limits imposed by offlabel clinical use of acetazolamide. Therefore, invasive CSF pressure readings were not performed during treatment. A prospective trial that incorporates noninvasive assessment of ICP, prior to and following each dose escalation, is being developed. The CSF pressure will be assessed using an MRI-based technique (magnetic resonance ICP [MRICP]).4 Previous successful applications in general hydrocephalous5 and more recently in shunted hydrocephalic patients6 justify the inclusion of MRICP scans in future studies of pharmacotherapy for iNPH. © 2014 American Academy of Neurology 1.
2.
3.
4.
5.
6.
Alperin N, Oliu CJ, Bagci AM, et al. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH. Neurology 2014;82:1347–1351. Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure: observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 1965;2:307–327. Ishikawa M, Hashimoto M, Mori E, et al. The value of the cerebrospinal fluid tap test for predicting shunt effectiveness in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 2012;9:1. Alperin NJ, Lee SH, Loth F, Raksin PB, Lichtor T. MR intracranial pressure (ICP): a method to measure intracranial elastance and pressure noninvasively by means of MR imaging: baboon and human study. Radiology 2000;217:877–885. Glick RP, Niebruegge J, Lee SH, et al. Early experience from the application of a noninvasive magnetic resonance imaging-based measurement of intracranial pressure in hydrocephalus. Neurosurgery 2006;59:1052–1060. Muehlmann M, Koerte IK, Laubender RP, et al. Magnetic resonance-based estimation of intracranial pressure correlates with ventriculoperitoneal shunt valve opening pressure setting in children with hydrocephalus. Invest Radiol 2013;48:543–547.
RISK FACTORS FOR EEG SEIZURES IN NEONATES TREATED WITH HYPOTHERMIA: A MULTICENTER COHORT STUDY
Steven M. Rothman, St. Louis: I was fascinated by the report by Glass et al.1 on EEG seizures in almost Neurology 83
November 4, 2014
1773
Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH Gordon J. Gilbert, Noam Alperin, Carlos Olio, et al. Neurology 2014;83;1773 DOI 10.1212/WNL.0000000000000994 This information is current as of November 3, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/19/1773.1.full.html
References
This article cites 6 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/19/1773.1.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
