Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen
Background: Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). Since the drug cannot cross the blood-brain barrier (BBB), it must be administered into the cerebrospinal fluid (CSF) space repeatedly by lumbar puncture. However, little is known...
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| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.01179/full |
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| author | Claudia D. Wurster Jan C. Koch Isabell Cordts Jens Dreyhaupt Markus Otto Zeljko Uzelac Simon Witzel Benedikt Winter Tugrul Kocak Michael Schocke Patrick Weydt Kurt Wollinsky Albert C. Ludolph Albert C. Ludolph Marcus Deschauer Paul Lingor Hayrettin Tumani Hayrettin Tumani Andreas Hermann Andreas Hermann René Günther René Günther |
| author_facet | Claudia D. Wurster Jan C. Koch Isabell Cordts Jens Dreyhaupt Markus Otto Zeljko Uzelac Simon Witzel Benedikt Winter Tugrul Kocak Michael Schocke Patrick Weydt Kurt Wollinsky Albert C. Ludolph Albert C. Ludolph Marcus Deschauer Paul Lingor Hayrettin Tumani Hayrettin Tumani Andreas Hermann Andreas Hermann René Günther René Günther |
| author_sort | Claudia D. Wurster |
| collection | DOAJ |
| description | Background: Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). Since the drug cannot cross the blood-brain barrier (BBB), it must be administered into the cerebrospinal fluid (CSF) space repeatedly by lumbar puncture. However, little is known whether ASOs have an impact on CSF routine parameters that may yield information on CSF flow and/or intrathecal inflammation. The objective of this study was to examine CSF routine parameters in SMA patients treated with nusinersen.Methods: Routine CSF parameters [white cell count, total protein, CSF/serum quotients of albumin (Qalb), lactate, and oligoclonal IgG bands (OCB)] of 60 SMA patients (type 1, 2, and 3, aged 7–60 years) were retrospectively analyzed.Results: White cells ranged from 0 to 4/μL in CSF; a singular case of pleocytosis (8/μL) was observed in a patient in parallel with a systemic infection. Total protein and Qalb showed a mild increase from baseline to the following lumbar punctures (except for total protein in CSF at the fourth injection of nusinersen). Lactate levels revealed a stable course. In one patient, positive OCB in CSF were transiently observed. The slight change in total CSF protein and Qalb may be caused by repeated lumbar puncture and/or intrathecal administration of the drug.Conclusion: Our data suggest that a regular examination of routine CSF parameters in patients in which intrathecal ASOs are administered is important to obtain information on possible side effects and to gain further insights into intrathecal processes. |
| first_indexed | 2024-12-19T06:29:26Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-19T06:29:26Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj.art-ea29c319a5254f108ea0190fc03ee2c72022-12-21T20:32:27ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-11-011010.3389/fneur.2019.01179482623Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With NusinersenClaudia D. Wurster0Jan C. Koch1Isabell Cordts2Jens Dreyhaupt3Markus Otto4Zeljko Uzelac5Simon Witzel6Benedikt Winter7Tugrul Kocak8Michael Schocke9Patrick Weydt10Kurt Wollinsky11Albert C. Ludolph12Albert C. Ludolph13Marcus Deschauer14Paul Lingor15Hayrettin Tumani16Hayrettin Tumani17Andreas Hermann18Andreas Hermann19René Günther20René Günther21Department of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, University Medicine Göttingen, Göttingen, GermanyDepartment of Neurology, Klinikum Rechts der Isar der Technischen Universität München, Munich, GermanyInstitute of Epidemiology and Medical Biometry, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, GermanyDepartment of Pediatrics, Ulm University, Ulm, GermanyDepartment of Orthopedic Surgery, RKU - University and Rehabilitation Clinics, Ulm University, Ulm, GermanyDepartment of Neuroradiology, RKU - University and Rehabilitation Clinics, Ulm University, Ulm, GermanyDepartment for Neurodegenerative Disorders and Gerontopsychiatry, Bonn University, Bonn, GermanyDepartment of Anesthesiology, RKU - University and Rehabilitation Clinics, Ulm University, Ulm, GermanyDepartment of Neurology, Ulm University, Ulm, Germany0German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, GermanyDepartment of Neurology, Klinikum Rechts der Isar der Technischen Universität München, Munich, GermanyDepartment of Neurology, Klinikum Rechts der Isar der Technischen Universität München, Munich, GermanyDepartment of Neurology, Ulm University, Ulm, Germany1Specialty Hospital of Neurology Dietenbronn, Schwendi, Germany2Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany3German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany4Department of Neurology, Technische Universität Dresden, Dresden, Germany5German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, GermanyBackground: Nusinersen is an antisense-oligonucleotide (ASO) approved for treatment of 5q-spinal muscular atrophy (SMA). Since the drug cannot cross the blood-brain barrier (BBB), it must be administered into the cerebrospinal fluid (CSF) space repeatedly by lumbar puncture. However, little is known whether ASOs have an impact on CSF routine parameters that may yield information on CSF flow and/or intrathecal inflammation. The objective of this study was to examine CSF routine parameters in SMA patients treated with nusinersen.Methods: Routine CSF parameters [white cell count, total protein, CSF/serum quotients of albumin (Qalb), lactate, and oligoclonal IgG bands (OCB)] of 60 SMA patients (type 1, 2, and 3, aged 7–60 years) were retrospectively analyzed.Results: White cells ranged from 0 to 4/μL in CSF; a singular case of pleocytosis (8/μL) was observed in a patient in parallel with a systemic infection. Total protein and Qalb showed a mild increase from baseline to the following lumbar punctures (except for total protein in CSF at the fourth injection of nusinersen). Lactate levels revealed a stable course. In one patient, positive OCB in CSF were transiently observed. The slight change in total CSF protein and Qalb may be caused by repeated lumbar puncture and/or intrathecal administration of the drug.Conclusion: Our data suggest that a regular examination of routine CSF parameters in patients in which intrathecal ASOs are administered is important to obtain information on possible side effects and to gain further insights into intrathecal processes.https://www.frontiersin.org/article/10.3389/fneur.2019.01179/fullspinal muscular atrophymotor neuron diseaseantisense-oligonucleotideroutine CSF parameterslumbar puncture |
| spellingShingle | Claudia D. Wurster Jan C. Koch Isabell Cordts Jens Dreyhaupt Markus Otto Zeljko Uzelac Simon Witzel Benedikt Winter Tugrul Kocak Michael Schocke Patrick Weydt Kurt Wollinsky Albert C. Ludolph Albert C. Ludolph Marcus Deschauer Paul Lingor Hayrettin Tumani Hayrettin Tumani Andreas Hermann Andreas Hermann René Günther René Günther Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen Frontiers in Neurology spinal muscular atrophy motor neuron disease antisense-oligonucleotide routine CSF parameters lumbar puncture |
| title | Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen |
| title_full | Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen |
| title_fullStr | Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen |
| title_full_unstemmed | Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen |
| title_short | Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen |
| title_sort | routine cerebrospinal fluid csf parameters in patients with spinal muscular atrophy sma treated with nusinersen |
| topic | spinal muscular atrophy motor neuron disease antisense-oligonucleotide routine CSF parameters lumbar puncture |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.01179/full |
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