The Timing of MRI Determines the Presence or Absence of Diffuse Pachymeningeal Enhancement in Patients with Spontaneous Intracranial Hypotension

Abstract

The timing and clinical relevance of diffuse pachymeningeal enhancement (DPE) in the magnetic resonance imaging (MRI) examination of patients with spontaneous intracranial hypotension (SIH) remain undetermined. We reviewed 53 consecutive SIH patients (30 F/23 M, mean age of onset 41.7 ± 11.3 years) in a tertiary hospital. Thirteen (24.5%) patients did not have DPE on their initial cranial MRIs. They had significantly shorter latency between the time of MRI examinations and the time of headache onset compared with those with DPE (6.5 ± 4.4 vs. 20.4 ± 16.3 days, t-test, P < 0.001). Eight of these 13 patients received a follow-up MRI (mean duration 30.3 ± 16.6 days, range 6-59 days) and six of them revealed DPE. Among patients with DPE, the enhancement disappeared as early as 25 days after headache onset. The outcome did not differ between patients with and without DPE. The presence of DPE was associated with the timing of the MRI examination.

Introduction

Spontaneous intracranial hypotension (SIH) is a syndrome characterized by postural headache. However, its manifestations are protean and sometimes characterized by atypical presentations, such as postural dizziness, exertional headache or mental decline (1), which may result in underdiagnosing this headache disorder (2) and highlights the importance of diagnostic imaging, especially cranial magnetic resonance imaging (MRI). The characteristic cranial MRI findings of SIH include diffuse pachymeningeal enhancement (DPE), brain descent and pituitary gland enlargement (1, 3). DPE is the most characteristic finding of SIH. Nevertheless, 7–29% of patients with SIH do not show DPE on their MRIs (4–6).

The determining factors related to DPE on brain MRIs in patients with SIH are not yet clear. One study failed to find any differences between SIH patients with and without DPE (7). One study has reported that a normal initial MRI might be related to a poor outcome (8). It has been our experience that patients without DPE on their initial MRIs usually show DPE at later evaluation. We therefore retrospectively investigated a large group of patients with SIH to determine whether the timing of MRI performance is related to DPE.

Methods

We retrospectively reviewed consecutive patients with SIH at Taipei-Veterans General Hospital (Taipei-VGH), a tertiary medical centre in Taiwan, between January 1998 and February 2007. Because there is no effective ‘gatekeeper’ for the healthcare delivery system in Taiwan (9), most of our SIH patients were self-referred or via our emergency department. Each patient completed a structured headache intake form during their first visit to our headache clinic or when admitted to our ward.

For study inclusion, the patients had to meet all the criteria for ‘headache attributed to spontaneous low CSF pressure’ proposed by the International Classification of Headache Disorders, 2nd edition (code 7.2.3) (ICHD-2) (10), except for criterion (D): headache resolves within 72 h after epidural blood patching (EBP) because not all patients received EBP. We excluded patients who had prior dural punctures, epi- or peridural anaesthesia, ventriculoperitoneal shunt or other causes of CSF fistula.

MRI examination

The MRI examination, both with and without administering intravenous contrast medium [gadopentetate dimeglumine (Gd) 0.1 mmol/kg b.w.], was performed on a 1.5-T system to all patients with the same methods. Brain images were obtained in the transverse plane with T1- and T2-weighted spin-echo sequences. The section thickness was 8 mm, with an acquisition matrix of 256 × 256. In order to evaluate DPE, post-Gd-enhanced T1-weighted images in the transverse plane were also obtained. We defined positive DPE as bilateral, diffuse, smooth and continuous pachymeningeal enhancement. The iter, i.e. the opening of the cerebral aqueduct, and cerebellar tonsil displacements were measured on the sagittal T1-weighted MRI scan to determine the degree of brain descent (11). The prepontine cistern space was defined by measuring the distance from clivus to mid-pons. The timing of the performance of the MRI studies was documented in relation to the onset of SIH symptoms, i.e. the appearance of postural headache. Some patients received heavily T2-weighted MR images to detect CSF leakage (12).

Treatment

Patients with SIH were given conservative treatments, such as hydration, and medications, including caffeine, theophylline, fludrocortisone and/or analgesics. If conservative treatments failed, EBP were performed. None of the patients received surgical repair for CSF leakage.

Follow-ups

We evaluated the recovery time based on reviewing patients' charts. We also conducted the Migraine Disability Assessment Score (MIDAS) questionnaire (13) either in person or by telephone interview to evaluate their current headache disability.

Statistics

SPSS Version 11.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Means were compared using unpaired t-test, and proportions were compared using χ² or Fisher's exact tests when appropriate. All P-values were two-tailed, and statistical significance was defined as a P-value of <0.05.

Results

Patients

During the study period, 53 consecutive patients (23 m/30 F, mean age 41.7 ± 11.3 years, age range 24–78 years) with SIH were reviewed. Some of them have been previously published (4, 12, 14–17). Clinical and radiographic features of the patient population are summarized in Table 1. Twenty-one patients received one brain MRI study, 28 patients received two studies, three received three studies and one patient four studies. Twenty-nine patients (54.7%) underwent the initial brain MRI examination within 2 weeks of headache onset. Forty (75.5%) of the 53 patients had DPE on their MRI, and 13 (24.5%) did not. The mean duration between headache onset and the initial MRI examinations was significantly longer in patients with DPE than in those without (20.4 ± 16.3 vs. 6.5 ± 4.4 days, t-test, P < 0.001). Eight of these 13 patients without DPE received a follow-up MRI examination (mean duration between headache onset and MRI examination 30.3 ± 16.6 days, range 6–59 days), six of whom (75%) revealed DPE. Four of these six patients with DPE had received a lumbar puncture, two before the first MRI and two between the first and second MRIs. The latency between lumbar puncture and second MRI ranged from 3 to 40 days. Of the 40 patients with DPE in their first MRI, 24 received at least one follow-up MRI examination, and DPE disappeared in 15 of these patients during the follow-up MRIs. Ten of these 40 (25%) patients had received lumbar puncture before their first MRIs. The mean latency between lumbar puncture and their first MRIs was 2.5 ± 1.3 days (range 1–5 days). The earliest disappearance of DPE was 25 days from headache onset, whereas the longest duration of DPE was 90 days from headache onset. One patient, a 52-year-old woman, had a very protracted course of low-pressure headache, and her MR myelography showed persistent CSF leakage. Her symptoms were mild, but persistent after three courses of epidural blood patches. A series of brain MRI studies showed a successive change in DPE: no appearance (day 11), appearance (day 28), regression (day 58) and disappearance (day 267) (Fig. 1).

Table 1

Demographic, clinical and imaging findings of study patients with spontaneous intracranial hypotension

	Patients with DPE (n = 40)	Patients without DPE (n = 13)	P-value
Mean age (years) (range)	41.9 ± 12.0 (25–78)	41.1 ± 9.3 (24–54)	0.823
Female (n (%))	20 (50%)	10 (76.9%)	0.089
Lumbar puncture	16 (40%)	10 (76.9%)	0.021
Mean CSF opening pressure (mmH2O) (range)	70.5 ± 48.4 (0–180)	46.9 ± 41.6 (10–125)	0.274
Mean interval (days) from headache onset to first MRI (range)	20.4 ± 16.3 (2–90)	6.5 ± 4.4 (1–13)	<0.001
MRI abnormalities
Mean distance from iter to incisural line (mm) (range)	−2.5 ± 4.4 (−10.3–6.6)	−1.9 ± 3.6 (−8.4–3.0)	0.685
Mean length from tonsil tip to the line of foramen magnum (mm) (range) 1.9 ± 5.5 (−7.8–12.1)	0.7 ± 2.9 (−5.8–6.6)		0.478
Mean length of prepontine cistern space (mm) (range)	3.9 ± 1.3 (0–7.5)	4.0 ± 1.6 (1.8–7.4)	0.803
Subdural fluid collection (n (%))	18 (45%)	1 (5.3%)	0.019
Patients who underwent MR myelography (n)	20 (50%)	8 (61.5%)	0.524
One level of spinal leakage (n (%))	10 (50%)	6 (75%)	0.352
Multiple levels of spinal leakage (n (%))	7 (35%)	1 (12.5%)
Treatment	6 (46.2%)	25 (62.5%)	0.299
Conservative only (n (%))	6 (46.2%)	25 (62.5%)	0.299
Epidural blood patches (n (%))	7 (53.8%)	15 (37.5%)
Mean interval (days) from onset to recovery (range)	43.5 ± 30.3 (6–150)	39.8 ± 22.8 (14–78)	0.685
Mean interval (days) from diagnosis to recovery (range)	22.9 ± 23.6 (2–86)	29.3 ± 19.7 (4–54)	0.389
Mean duration (months) of follow-up	33.8 ± 27.4 (3–94)	34.8 ± 35.2 (3–95)	0.912
Mean Migraine Disability Assessment Score	0.4 ± 0.7 (0–3)	0.1 ± 0.3 (0–1)	0.077

DPE, Diffuse pachymeningeal enhancement.

Figure 1

Gadolinium-enhanced coronal magnetic resonance imaging in a 52-year-old woman with spontaneous intracranial hypotension. (a) Day 11 after headache onset, no abnormal pachymeningeal enhancement. (b) Day 28, prominent bilateral pachymeningeal enhancement. (c) Day 58, pachymeningeal enhancement is regressed. (d) Day 267, pachymeningeal enhancement disappears.

The degree of brain descent and prepontine cistern space did not differ between patients with and without DPE in their initial MRIs. Patients with DPE in their initial MRIs had a significantly higher proportion of subdural fluid collections (including subdural haematoma and non-haemorrhagic subdural collections) compared with those without enhancement (45.0% vs. 5.3%, Fisher's exact test, P = 0.019). Twenty-eight patients underwent MR myelography examination (12), 24 of whom showed at least one leakage site. The proportion of negative findings, single leakage site and multiple leakage sites did not differ between patients with and without DPE.

The mean duration of follow-up was 34.1 ± 29.2 months (range 3–96 months). Overall, 50 patients (94.3%) had a good outcome after hydration and/or EBP within 3 months. Only three patients did not have satisfactory outcomes, and one of them did not have a DPE in the initial MRI. The MIDAS questionnaire was completed in 48 patients (90.6%); only 10 still had some infrequent, non-orthostatic headaches, and all MIDAS scores were between 0 and 5, i.e. ‘minimal disability’ (13).

Discussion

To our knowledge, this is the largest study to evaluate the timing of appearance of DPE in patients with SIH. Consistent with a previous study (18), we found that absence of DPE could not exclude the diagnosis of SIH. In contrast with two previous studies (7, 8), we found patients without DPE in their initial MRIs usually had both a shorter latency between MRI examination and their headache onset and a lower proportion of subdural fluid collections.

Our previous study found that the latency between the MRI examinations and headache onset was longer for patients with subdural fluid collections compared with those without (16). The lower frequency of subdural fluid collections in patients without DPE in their initial MRIs suggested that they might either be in the early stage of SIH or have a less severe disease.

It is thought that the development of DPE is due to a compensatory pachymeningeal venous engorgement and therefore results in a greater concentration of gadolinium in the dural vasculature and interstitial fluid (3). The finding that some patients did not show DPE initially but developed them at a later time suggests that development of DPE may take a certain amount of time in some patients. These patients might not have quantitatively sufficient compensatory venous engorgement to result in DPE at the beginning. In two patients, we also found that the DPE disappeared even though CSF leakage persisted. Therefore, a new balance might be achieved between whole intracranial CSF and blood volume, and accordingly the compensatory venous engorgement disappears.

Our findings showed that the timing of DPE varied widely, which demonstrates the high degree of variability in the disease course. This explains why previous studies (7, 8) have failed to find an association between the timing of MRIs and meningeal abnormalities. Two previous studies have also shown that patients with DPE had a longer time interval from headache onset to MRI examination compared with patients without (Chung et al.: 18.9 ± 19.7 days vs. 10.7 ± 9.2 days; Schievink et al.: 4 weeks vs. 3 weeks) (7, 8). The small case number and wide range in duration of MRI examinations may have also caused the results to be statistically insignificant.

For the four patients who had a DPE in their second MRI and had a lumbar puncture before their second MRI, we can not exclude the possibility that the lumbar puncture might have contributed in part to the appearance of the DPE. However, two patients who did not receive lumbar punctures still showed DPEs later.

Our data have shown that SIH patients with a normal initial cranial MRI had at least a similarly good outcome to those with abnormal MRIs. This finding is different from the study results of Schievink et al., who have reported a better outcome (97%) in patients with an abnormal MRI than in those (14%) with a normal MRI (9). They also found that all patients with a normal initial MRI had multiple spinal CSF leaks, which explained their poor prognosis (8). Two points might explain the discrepancy between their study and our study. One point of discrepancy is the selection bias; the patients presented by Schievink et al. were seen in a neurosurgical centre with a focus on the surgical repair of CSF leaks. Therefore, their findings may not generalize. Second, the number of patients with a normal cranial MRI is only a small part of the total SIH patients. Larger numbers of patients are needed before any conclusions can be drawn.

In conclusion, the appearance of DPE was related to the timing of MRI examination and was possibly due to disease severity. Some patients took a longer time to develop DPE. Whether the appearance of DPE in the initial brain MRIs is related to the outcome needs to be examined with further prospective controlled studies.