Current affiliation : Department of Neurosurgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
Nontraumatic subdural hematoma (SDH) is a common disease, and spinal cerebrospinal fluid (CSF) leakage is a possible etiology of unknown significance, which is commonly investigated by several invasive studies. This study demonstrates that heavily T2-weighted magnetic resonance myelography (HT2W-MRM) is a safe and clinically effective imaging modality for detecting CSF leakage in patients with nontraumatic SDH.
All patients who underwent HT2W-MRM for nontraumatic SDH workup at our institution were searched and enrolled in this study. Several parameters were measured and analyzed, including patient demographic data, initial modified Rankin Scale (mRS) score upon presentation, SDH bilaterality, hematoma thickness upon presentation, CSF leakage sites, treatment modalities, followup hematoma thickness, and follow-up mRS score.
Forty patients were identified, of which 22 (55.0%) had CSF leakage at various spinal locations. Five patients (12.5%) showed no change in mRS score, whereas the remaining (87.5%) showed decreases in follow-up mRS scores. In terms of the overall hematoma thickness, four patients (10.0%) showed increased thickness, two (5.0%) showed no change, 32 (80.0%) showed decreased thickness, and two (5.0%) did not undergo follow-up imaging for hematoma thickness measurement.
HT2W-MRM is not only safe but also clinically effective as a primary diagnostic imaging modality to investigate CSF leakage in patients with nontraumatic SDH. Moreover, this study suggests that CSF leakage is a common etiology for nontraumatic SDH, which warrants changes in the diagnosis and treatment strategies.
Chronic subdural hematoma (SDH) is a well-known disease of elderly individuals as trauma-related intracranial hemorrhage expanded by various mechanisms, including rebleeding, coagulopathy, local inflammation and angiogenesis, exudate from outer membrane, and cerebrospinal fluid (CSF) entrapment [
Among various possible etiologies for nontraumatic SDH, many studies have investigated the association between spontaneous intracranial hypotension (SIH), a syndrome induced by the leakage of CSF from dural tear and SDH [
Studies have used invasive modalities to identify CSF leakage sites, such as radionuclide cisternography, computed tomography (CT) myelography, and magnetic resonance myelography (MRM) with contrast agent [
Heavily T2-weighted MRM (HT2W-MRM) without intrathecal contrast injection is an emerging noninvasive modality to precisely detect CSF leakage sites [
This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2008-631-103), and the requirement for informed consent from the patients was waived.
Our institution introduced HT2W-MRM in August 2018 as a single primary imaging method for investigating CSF leakage [
We reviewed our institution’s electronic medical records and identified 73 patients who 1) had undergone HT2W-MRM and simultaneously 2) had been diagnosed with SDH using any diagnostic imaging modality. Among the 73 identified patients, 33 patients who had an obvious etiology of SDH other than CSF leakage, such as head trauma, any cranial or spinal surgeries within 6 months, and any hematologic disorders, were excluded. Finally, 40 patients with nontraumatic SDH who underwent HT2W-MRM to determine CSF leakage or SIH were enrolled in this study.
Several parameters were described regarding the patients’ initial presentation. The patients’ overall neurological status was defined using the modified Rankin Scale (mRS) and categorized as independent (for mRS grades 0–2) and dependent (for mRS grades 3–5). SDH location (bilaterality) and maximal thickness were measured using the initial CT or MRI upon the first presentation. CSF leakage sites were specified using HT2W-MRM and categorized as single/multiple and cervical/thoracic/lumbar.
HT2W-MRM is mostly prescribed and used in two situations in Seoul National University Bundang Hospital. First, when SIH is clinically suspected from neurology outpatient clinic or emergency department visit, HT2W-MRM is performed as the primary investigation procedure. Second, for patients diagnosed with SDH, if CSF leakage is suspected as a probable cause, HT2W-MRM is prescribed by neurosurgeons.
Technically, the machine used to perform HT2W-MRM is a 3.0 T MR unit with a routine protocol of heavily T2-weighted sagittal, fat-suppressed three-dimensional (3D) fast spinecho pulse sequence. Two sequences of sagittal 3D images were separately acquired for the cranial and caudal spines; then, multiplanar reformation was performed for axial and coronal images [
Whenever CSF leakage is revealed on MRI, fluoroscopy-guided EBP is performed by interventional radiologists on a referral basis. The EBP procedure uses a mixture of autologous blood and 1 mL of contrast agent (Omnipaque 300; GE Healthcare, Boston, MA, USA) at a maximum of 10 mL per injection. Targeted EBP procedures are performed after confirming one or more CSF leakage levels using HT2W-MRM, either at the specific CSF leakage level, at the center of the segmental leak, or at two sites to sufficiently cover diffuse or multifocal leaks [
Hematoma removal operation, EBP, middle meningeal artery embolization (MMAE), or a combination of these procedures was decided by the attending neurosurgeons [
The SDH resolution was defined as the maximum follow-up hematoma thickness of less than 5 mm. A favorable clinical outcome was defined as a follow-up mRS grade of 0–2.
Statistical analyses were performed using R (version 4.0.0; open-source software,
The mean age of the 40 enrolled patients was 62.9±15.0 years, of which 31 (77.5%) were male. The 95% confidence interval for the proportion of males was 61.5–89.2%, indicating statistically significant male predominance. Nineteen patients (47.5%) were categorized as independent (initial mRS grade of 0–2), whereas the remaining 21 (52.5%) belonged to the dependent (initial mRS grade of 3–5) group. Eleven patients (27.5%) showed unilateral SDH with a mean maximal SDH thickness of 17.45±8.41 mm, whereas 29 (72.5%) showed bilateral SDH and had a mean maximal SDH thickness of 25.6±13.5 mm. Eighteen (45.0%) had no CSF leakage on HT2W-MRM. The remaining patients (n=22, 55.0%) had various CSF leakage sites ranging from single to diffuse spinal level. Among the 22 patients with CSF leakage, six had single leakage lesions (three, two, and one for cervical, thoracic, and lumbar sites, respectively), and 16 had multiple leakage lesions (one, five, two, two, and six for cervical, cervicothoracic, thoracic, thoracolumbar, and cervicothoracolumbar sites, respectively). Patient characteristics are summarized in
Among the 22 and 18 patients with and without CSF leakage, 16 (72.7%) and 13 (72.2%) presented bilateral SDH, respectively. The chi-square test did not show statistical differences between CSF leakage and bilaterality (
Among the 22 patients with CSF leakage, 10 underwent both hematoma removal operation and EBP (
Among the 18 patients who did not demonstrate CSF leakage on HT2W-MRM, 10 underwent hematoma removal operation : only six (60.0%) had SDH resolution and nine (90.0%) had favorable clinical outcomes. For five patients, the wait-and-see strategy was used, including one patient who had a follow-up clinic visit without undergoing an imaging study. Two (40.0%) of them showed SDH resolution, and all of them (100.0%) had favorable clinical outcomes. One patient underwent MMAE only and showed favorable clinical outcomes, but no SDH resolution. Two patients underwent empirical EBP at the suspicious level under clinical correlation of symptoms. One patient underwent both hematoma removal operation and empirical EBP and showed both SDH resolution and favorable clinical outcomes. One patient underwent empirical EBP only and showed favorable clinical outcomes, but no SDH resolution.
Among all patients in this study, except for two who did not undergo a follow-up imaging study, four (10.0%) showed an increase in hematoma thickness. Two of them had demonstrated CSF leakage on HT2W-MRM at the initial presentation and necessitated further treatment due to an increase in hematoma size despite undergoing EBP with or without hematoma removal operation. Furthermore, two of them showed no CSF leakage on HT2W-MRM, but hematoma size increased following hematoma removal operation and conservative management, followed by readmission and burr hole surgery.
Among all patients in this study, five (12.5%) showed no changes in mRS grade, with one having mRS grade 4, one having mRS grade 0, and three having mRS grade 1 (
Neurosurgeons commonly encounter SDH in the clinical setting, and treatment outcomes are not always favorable due to little advancement in the treatment modalities for SDH. Although socioeconomic factors would influence the treatment course and outcomes of patients with SDH, multiple studies have demonstrated a sizable percentage of mortality (3–8%) and morbidity (5–12%) [
This study’s primary focus was nontraumatic SDH possibly caused by SIH, as our concern was that SIH as a cause of SDH is underestimated and undertreated. SIH prevalence in USA is supposedly 5 per 100000 according to one observational study [
Previously, CSF leakage was evaluated using a few imaging modalities, such as MR myelography, CT myelography, and radioisotope scintigraphy, with CT myelography as the current gold standard [
In addition, our data showed another important finding that 55% of patients had CSF leakage, suggesting that CSF leakage might be underestimated as a cause of nontraumatic SDH and requires good clinical suspicion of neurosurgeons at the diagnosis stage. It is undeniable that selection bias might play a role for patients with poor general condition which precludes transfer for MRI. However, besides those rare cases, as high as 55.0% of CSF-leakage detection among our study subjects possibly stems from increased application of HT2W-MRM at our institution, as all nontraumatic cases with even small possibility of SIH underwent HT2W-MRM. Further study is warranted to reveal the percentage of patients with CSF leakage among patients with nontraumatic SDH, for which current study is not specifically designed to prove. Therefore, we suggest using HT2W-MRM early as the primary CSF leakage detection modality in patients with nontraumatic SDH to further change the diagnosis and treatment strategies.
This study has few limitations. First, HT2W-MRM is not the gold standard in the diagnosis of CSF leakage site due to its innate nature. HT2W-MRM only detects the already extravasated CSF in the epidural space, which might not correspond to active leakage points as the CSF can travel throughout the epidural space. Thus, although the clinical outcomes of using HT2W-MRM were favorable in this study, dynamic imaging modalities, such as dynamic myelography and digital subtraction myelography, could be necessary. Second, as the decision to start or the timing of the HT2W-MRM study is dependent solely on the physician without an established protocol, not all patients with nontraumatic SDH possibly caused by CSF leakage were included in the study. Further study eliminating this selection bias is warranted.
HT2W-MRM is a safe and effective diagnostic modality for CSF leakage in patients with nontraumatic SDH. Furthermore, CSF leakage could be a common etiology of nontraumatic SDH than our knowledge, which warrants further investigations.
No potential conflict of interest relevant to this article was reported.
This type of study does not require informed consent.
Conceptualization : SA, TK
Data curation : SA
Methodology : SA, TK
Project administration : TK
Visualization : SA
Writing - original draft : SA
Writing - review & editing : TK, HGJ, DS, HJ, SUL, JSB, CWO
Patient selection and subgrouping flowchart. Number inside bracket represents patient count. HT2W-MRM : heavily T2-weighted magnetic resonance myelography, SDH : subdural hematoma, CSF : cerebrospinal fluid, Op : hematoma removal operation, EBP : epidural blood patch, Embo : middle meningeal artery embolization.
A-C : Stacked bar chart for mRS grade change from initial presentation to the latest follow up visit within 6 months. Graph legend on the right side indicates bar colors assigned to each mRS grades. Each number at the center of the bar indicates patient count for specific mRS grades. mRS : modified Rankin Scale.
Patient characteristics
Total (n=40) | CSF leakage (+) (n=22) | CSF leakage (-) (n=18) | ||
---|---|---|---|---|
Age (years) | 62.9±15.0 | 65.6±12.7 | 59.6±17.2 | 0.221 |
Sex, male | 31 (77.5) | 16 (72.7) | 15 (83.3) | 0.476 |
Initial mRS | 0.356 | |||
Independent, ≤2 | 19 (47.5) | 9 (40.9) | 10 (55.6) | |
Dependent, >2 | 21 (52.5) | 13 (59.1) | 8 (44.4) | |
Bilateral SDH | 29 (72.5) | 16 (72.7) | 13 (72.2) | 0.945 |
CSF leakage | ||||
Single cervical | 3 (7.5) | 3 (13.6) | ||
Single thoracic | 2 (5.0) | 2 (9.1) | ||
Single lumbar | 1 (2.5) | 1 (4.5) | ||
Multiple cervical | 1 (2.5) | 1 (4.5) | ||
Multiple cervico-thoracic | 5 (12.5) | 5 (22.7) | ||
Multiple thoracic | 2 (5.0) | 2 (9.1) | ||
Multiple thoraco-lumbar | 2 (5.0) | 2 (9.1) | ||
Multiple cervico-thoraco-lumbar | 6 (15.0) | 6 (27.3) | ||
Treatment modalities | ||||
Hematoma removal operation | 22 (55.0) | 11 (50.0) | 11 (61.1) | |
EBP | 23 (57.5) | 21 (95.5) | 2 (11.1) | |
MMAE | 3 (7.5) | 2 (9.1) | 1 (5.6) | |
Follow up mRS | 1.000 | |||
Favorable,≤2 | 38 (95.0) | 21 (95.5) | 17 (94.4) | |
Poor, >2 | 2 (5.0) | 1 (4.5) | 1 (5.6) |
Values are presented as mean±standard deviation or number (%). CSF : cerebrospinal fluid, mRS : modified Rankin Scale, SDH : subdural hemorrhage, EBP : epidural blood patch, MMAE : middle meningeal artery embolization
SDH thickness measurements
Total (n=40) | CSF leakage (+) (n=22) | CSF leakage (-) (n=18) | |
---|---|---|---|
Unilateral SDH | 11 | 6 | 5 |
Initial (mm) | 17.5±8.41 | 17.7±7.74 | 17.2±10.1 |
Follow up (mm) | 6.2±9.37 | 10.2±11.5 | 1.6±2.3 |
Change (mm) | -11.2±10.9 | -7.5±11.5 | -15.6±9.24 |
Bilateral SDH | 29 | 16 | 13 |
Initial (mm) | 25.6±13.5 | 25.7±16.4 | 25.5±9.39 |
Follow up (mm) | 11.8±11.6 |
9.47±12.4 |
14.7±10.2 |
Change (mm) | -15.1±11.2 |
-17.5±10.8 |
-12.2±11.3 |
Values are presented as mean±standard deviation.
Measured for 27 patients except two patients without follow up imaging.
Measured for 15 patients except one patient without follow up imaging.
Measured for 12 patients except one patient without follow up imaging.
SDH : subdural hemorrhage, CSF : cerebrospinal fluid