More than "just" a headache
The burden of spinal CSF leaks
Volz et al. Cephalalgia 2023
SIH and PDPH are widely unknown, under-, and misdiagnosed. „It‘s just a headache“ – that is a common perception. Many patients spent months, even years of their lifes before the diagnosis of this treatable disease is made.
AIMs
- to assess disease and mental health burden in spinal CSF leaks.
- to asess outcome that is relevant to the patient
- to provide access to evidence
Publications:
Volz et al. More than a headache—somatic and mental symptom burden in spontaneous intracranial hypotension before and after surgical treatment. Front. Neurol., 08 October 2024. doi.org/10.3389/fneur.2024.1421579
Urbach et al. Spinal dementia: Don't miss it, it's treatable. Neuroradiology. 2024 July 10. doi:10.1007/s00234-024-03425-9
Volz F, et al. Impact of Spinal CSF Leaks on Quality of Life and Mental Health and Long-Term Reversal by Surgical Closure. Neurol Clin Pract. 2024 Apr;14(2):e200272. doi: 10.1212/CPJ.0000000000200272
Volz, F. et al. Don’t delay, but don’t despair: symptom duration, comorbidity and outcome after closure of spinal cerebrospinal fluid leaks. J Neurol (2024). https://doi.org/10.1007/s00415-024-12242-2
Volz F, et al. Recovery and long-term outcome after neurosurgical closure of spinal CSF leaks in patients with spontaneous intracranial hypotension. Cephalalgia. 2023 Aug;43(8):3331024231196808. doi: 10.1177/03331024231195830.
Jesse et al. Patient-reported symptomatology and its course in spontaneous intracranial hypotension - Beware of a chameleon. Clin Neurol Neurosurg. 2023 Dec 19:236:108087.doi: 10.1016/j.clineuro.2023.108087
Kraus LM et al. Chronic post-dural puncture headache – a serious and underrated complication with a major impact on social life. Abstract. Brain and Spine 2923 3:101958. doi: 10.1016/j.bas.2023.101958
Dobrocky T, et al.. Spontaneous intracranial hypotension: searching for the CSF leak. Lancet Neurol. 2022 Apr;21(4):369-380. doi: 10.1016/S1474-4422(21)00423-3.
Jesse CM, et al. The impact of spontaneous intracranial hypotension on social life and health-related quality of life. J Neurol. 2022 Oct;269(10):5466-5473. doi: 10.1007/s00415-022-11207-7.
Review:
Zander C. et al. Spontaneous intracranial hypotension - a spinal disease. RöFo 2024 June, doi:10.1055/a-2318-8994
Urbach H,et al. Spontaneous Intracranial Hypotension. Dtsch Arztebl Int. 2020 Jul 6;117(27-28):480-487. doi: 10.3238/arztebl.2020.0480.
Therapy
What can we do better?
Beck et al. 2018
Spinal CSF Leaks
Spinal CSF leaks can and should be treated. First attempt for symptomatic releave should be a high-volume bloodpatch. In PDPH this can essentially heal the patient.
In case of persistent CSF leak, as in SIH, we aim for a targeted approach to prevent long-term sequelae as subdural hematoma, superficial siderosis, bibrachial amyotrophy, and coma.
AIMs
- to sufficiently seal the leak at lowest risks
Publications:
El Rahal et al: Safety, Sequelae, and Efficacy of Nerve Root Clipping in Patients With Spontaneous Spinal Cerebrospinal Fluid Leaks. Operative Neurosurgery ():10.1227/ons.0000000000001401, October 22, 2024. | DOI: 10.1227/ons.0000000000001401
Volz et al. Keyhole Fenestration for Cerebrospinal Fluid Leaks in the Thoracic Spine: Quantification of Bone Removal and Microsurgical Anatomy. Operative Neurosurgery. December 22, 2023. doi: 10.1227/ons.0000000000001042
Piechowiak EI, et al. Epidural Blood Patching in Spontaneous Intracranial Hypotension-Do we Really Seal the Leak? Clin Neuroradiol. 2023 Mar;33(1):211-218. doi: 10.1007/s00062-022-01205-7.
Beck J, et al. Minimally invasive surgery for spinal cerebrospinal fluid leaks in spontaneous intracranial hypotension. J Neurosurg Spine. 2022 Sep 9;38(1):147-152. doi: 10.3171/2022.7.SPINE2252.
Häni L, et al. Outcome after surgical treatment of cerebrospinal fluid leaks in spontaneous intracranial hypotension-a matter of time. J Neurol. 2022 Mar;269(3):1439-1446. doi: 10.1007/s00415-021-10710-7.
Beck J, et al. Posterior Approach and Spinal Cord Release for 360° Repair of Dural Defects in Spontaneous Intracranial Hypotension. Neurosurgery. 2019 Jun 1;84(6):E345-E351. doi: 10.1093/neuros/nyy312. PMID: 30053151.
Beck J, et al. Diskogenic microspurs as a major cause of intractable spontaneous intracranial hypotension. Neurology. 2016 Sep 20;87(12):1220-6. doi: 10.1212/WNL.0000000000003122.
Imaging
Expand the perspectiveOur imaging-based approaches are founded on successful collaboration of several departments:
In the Department of Neuroradiology, the team of Prof. Dr. Urbach and Dr. Lützen work continously to improve different techniques to detect spinal CSF leaks, With the Department of Nuclear Medicine and Prof. Dr. Dr. Meyer, we aim to improve diagnostic marker for spinal CSF leaks.
In collaboration with the Devision of Medical Physics, Prof. Dr. Zeitsev, Dr. Reisert, Department of Neurosurgery, Dr. Wolf, Department of Neuroradiology, Prof. Urbach, Dr. Demerath - automated analysis and postprocessing pipelines (www.nora-imaging.org), non-invasive dynamic measures (phase-contrast MRI), and diffusion microstructure imaging (DMI) are applied to extend our knowledge on pathomechanisms and to explore further imaging-derived biomarker.
Detection of spinal CSF leaks
It is our goal to investigate new methods, and ultimately improve sensitivity and specificity to detect spinal CSF leaks. While SIH can be detected in most cases, we are still nearly „blind“ detecting PDPH.
AIMs
- to better understand pathomechanisms
- to reduce radiation dose
- to improve diagnostic pathways
- to improve reliability
Publications:
Lützen et al. Primary CSF-lymphatic fistula: a previously unknown cause of spontaneous intracranial hypotension. J Neurol 271, 7016–7020 (2024). https://doi.org/10.1007/s00415-024-12598-5.
Lützen N, Demerath T, Volz F, Beck J, Urbach H. Cone-Beam CT for the Detection of a Ventral Spinal CSF Leak in Spontaneous Intracranial Hypotension. Neurology. 2023 Jul 27:10.1212/WNL.0000000000207504.
Lützen N, et al. Prone Dynamic CT Myelography in Spontaneous Intracranial Hypotension: Diagnostic Need and Radiation Doses. Clin Neuroradiol. 2023 Sep;33(3):739-745. doi: 10.1007/s00062-023-01269-z.
Lützen N, Beck J, Urbach H. Cerebrospinal Fluid Venous Fistula Imaging with Ultrahigh-Resolution Cone-Beam Computed Tomography. JAMA Neurol. 2023 Aug 1;80(8):870-871.
Lützen N, et al. Sacral Dural Tears as a Cause of Spontaneous Intracranial Hypotension. Clin Neuroradiol. 2023 Jun 1. doi: 10.1007/s00062-023-01292-0.
Lützen N, et al.. Spontaneous intracranial hypotension: diagnostic and therapeutic workup. Neuroradiology. 2021 Nov;63(11):1765-1772. doi: 10.1007/s00234-021-02766-z
Arnold PG, et al. Support Vector Machine-based Spontaneous Intracranial Hypotension Detection on Brain MRI. Clin Neuroradiol. 2022 Mar;32(1):225-230.
Evangelou P, et al. 68Ga-DOTA PET for Diagnosis of Spinal Cerebrospinal Fluid Leaks. J Nucl Med. 2023 Mar;64(3):430-436. doi: 10.2967/jnumed.122.264059
phase-contrast MRI
By this non-invasive method, velocities of a substance or movement of a structure, here CSF and CNS, can be assessed. This time-resolved velocity data can be used to derive further dynamik biomarker in SIH, IIH, and iNPH without interference to the system. (DRKS00017351)
AIMs
- to better understand pathomechanisms
- to improve diagnostic pathways
Publications:
Wolf K, et al. Non-invasive biomarkers for spontaneous intracranial hypotension (SIH) through phase-contrast MRI. J Neurol (2024). https://doi.org/10.1007/s00415-024-12365-6
Wolf K, et al. CSF Flow and Spinal Cord Motion in Patients With Spontaneous Intracranial Hypotension: A Phase Contrast MRI Study. Neurology. 2023 Feb 14;100(7):e651-e660. doi: 10.1212/WNL.0000000000201527.
Beltrán S, et al. Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants. NMR Biomed. 2023 Aug 3:e5013. doi: 10.1002/nbm.5013.
Wolf K, et al. Idiopathische intrakranielle Hypertension und Phasenkontrast-MRT: ein neuer Ansatz. Clin Neuroradiol 33 (Suppl 1),1-140(2023).https://doi.org/10.1007/s00062-023-01336-5
Wolf K, et al. Spinal cord motion assessed by phase-contrast MRI - An inter-center pooled data analysis. Neuroimage Clin. 2023;37:103334. doi: 10.1016/j.nicl.2023.103334.
Wolf K, et al. Focal cervical spinal stenosis causes mechanical strain on the entire cervical spinal cord tissue - A prospective controlled, matched-pair analysis based on phase-contrast MRI. Neuroimage Clin. 2021;30:102580. doi: 10.1016/j.nicl.2021.102580
Wolf K, et al. Spinal Cord Motion in Degenerative Cervical Myelopathy: The Level of the Stenotic Segment and Gender Cause Altered Pathodynamics. J Clin Med. 2021 Aug 25;10(17):3788. doi: 10.3390/jcm10173788.
Biomarker
machanics or metabolism?
Why does a person develop SIH or PDPH? Are there risk factors? Do we need to look beyond mechanics? Might we be able to detect and monitor spinal CSF leaks by a drop of blood?
The analysis of fluid-derived biomarker, and tissue will help to answer these questions.
AIMs
- to monitor markers for superficial siderosis in spinal CSF leaks, which is a common long-time sequelae of intracranial hypotension causing neurological deterioration.
- to implement proteomics and transcriptomics to depict possible diagnostic and therapeutic targets
Current Project:
The objective of the P-InSIHght study is to explore the utility of proteomics as a diagnostic and investigative tool in SIH. Through large-scale protein analysis of samples from SIH patients and controls, the research group aim to identify biomarkers that can provide insight into the pathology of SIH and potentially serve as a non-invasive diagnostic criterion and even as a follow-up tool.
Publications:
Häni L, et al. Cerebrospinal fluid biomarkers of superficial siderosis in patients with spontaneous intracranial hypotension. Eur J Neurol. 2023 Jan;30(1):235-240. doi: 10.1111/ene.15591. Epub 2022 Oct 19. PMID: 36209476.
El Rahal A, et al. Surgical closure of spinal CSF leaks improves symptoms in patients with superficial siderosis. Eur J Neurol. 2023 Nov 28. doi: 10.1111/ene.16122.
Histology
tackling pathomechanisms in spinal CSF leaks
Understanding spinal CSF leaks
In collarboration with the Institute for Neuropathology, we aim to understand the pathomechanisms of spinal CSF leaks. What happens inside the spinal canal that prevents the dura from healing? what is the exact histology of CSF leaks?
AIMs
- to better understand pathomechanisms of spinal CSF leaks
- to improve diagnostic pathways
- to improve treatment pathways
Publications:
Urbach H, et al. Different Glymphatic Kinetics in Spontaneous Intracranial Hypotension. AJNR Am J Neuroradiol. 2024 Oct 3;45(10):1605-1612. doi: 10.3174/ajnr.A8365.
Häni L et al. Distinct Pattern of Membrane Formation With Spinal Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension. Operative Neurosugery 2023. Sep doi: 10.1227/ons.0000000000000914
CSF Circulation
the medical panta rhei
phase-contrast MRI - color-coded velocities in head-feed direction
The traditional concepts of CSF production, resorption, and function have been challenged over the last years. The maintainance of CSF circulation is beliefed as being crucial for the function of the brain. Thus, understanding these machnisms is highly important in diseases related to impaired CSF circulation.
There are few non-invise approaches, as phase-contrast MRI, that allow a glimps into the system without any outer manipulation.The standard procedure to investigate parameters of CSF circulation is infusion testing.
In disorders with impaired CSF circulation, the infusion test serves as a diagnostic tool based on established markers. Yet many aspects are not fully understood.
AIMs
- to investigate markers of CSF circulation
- to investigating non-invasive tools as potential substitute for infusiontest (https://interfacegroup.ch)
Publications:
Karimi F, et al. Theory for a non-invasive diagnostic biomarker for craniospinal diseases. Neuroimage Clin. 2023;37:103280. doi: 10.1016/j.nicl.2022.103280.
Kraus LM et al. A chronic post dural puncture syndrome without low opening pressure or altered CSF dynamics. Abstract. Brain and Spine 3:101914. doi:10.1016/j.bas.2023.101914
Häni L, et al. Insights into the natural history of spontaneous intracranial hypotension from infusion testing. Neurology. 2020 Jul 21;95(3):e247-e255. doi: 10.1212/WNL.0000000000009812.
Beck J, et al. Cerebrospinal fluid outflow resistance as a diagnostic marker of spontaneous cerebrospinal fluid leakage. J Neurosurg Spine. 2017 Aug;27(2):227-234. doi: 10.3171/2017.1.SPINE16548.
Research requires strong collaborations across specialties and borders. This page represents efforts of the interdisciplinary CSF Team in collaboration with
University of Freiburg:
Department of Neurosurgery
Department of Neuroradiology
Department of Radiology, Medical Physics
Department of Nuclear Medicine
Department of Neuropathology
Department of Anaesthesiology
Department of Opthalmology, Section Neuroopthalmology
Swiss:
Department of Neuroradiology, Inselspital, Bern
Department of Neurosurgery, Inselspital Bern
Department of Physiology, the interface group, UZH Zürich
UK:
King's College, London
University College of London
USA:
Stanford Medical, CA
Cedars-Sinai Medical Center, CA
Denmark:
Danish Headache Center, Copenhagen