G Model
ADVMS 36 1–4 Advances in Medical Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Advances in Medical Sciences journal homepage: www.elsevier.com/locate/advms 1 2 3 4 5 6 7 8 9
Original Research Article
Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension Ohwaki a,*, Eiji Yano a, Takayuki Shinohara b, Takehiro Watanabe b, Akiko Ogawa b, Norio Fujii b, Tadayoshi Nakagomi b
Q1 Kazuhiro
a b
Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 February 2013 Accepted 19 December 2013 Available online xxx
Purpose: Although many studies have described various features of neuroimaging tests associated with intracranial hypotension, few have examined their validity and reliability. We evaluated the association between CSF leaks detected by radionuclide cisternography and abnormal MRI findings in the accurate diagnosis of intracranial hypotension. Patients/methods: We retrospectively assessed 250 patients who were suspected of intracranial hypotension and underwent subsequent radionuclide cisternography. We obtained 159 sagittal and 153 coronal T2-weighted MRI images and 101 gadolinium-enhanced T1-weighted MRI images. We assessed the CSF leaks in relation to a sagging brain, the maximum subdural space in sagittal and coronal images, and dural enhancement. Results: Overall, 186 (74%) patients showed CSF leaks on radionuclide cisternography. A sagging brain was observed in 21 (13%) of the 159 patients with sagittal MRIs. A sagging brain was not associated with CSF leaks (14% vs. 10%; p = 0.49). Compared to patients without CSF leaks, those with CSF leaks tended to have a larger maximum subdural space in both the sagittal (3.7 vs. 4.1 mm) and coronal (2.5 vs. 2.8 mm) images; however, the differences were not significant (p = 0.18 and p = 0.53, respectively). Dural enhancement was observed only in one patient, who presented with CSF leaks on radionuclide cisternography. Conclusions: Our study, which included a relatively large population, did not find any association between the findings of radionuclide cisternography and MRI. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately. ß 2014 Published by Elsevier Urban & Partner Sp. z o.o. on behalf of Medical University of Bialystok.
Keywords: Intracranial hypotension Magnetic resonance imaging Cerebrospinal fluid Radionuclide imaging Headache
10 11
1. Introduction
12 13 14 15 16 17 18
Once considered an exceedingly rare disorder, intracranial hypotension has recently been identified as an important cause of persistent headaches. It is characterized by orthostatic headache and low cerebrospinal fluid (CSF) pressure. However, the nature of intracranial hypotension remains largely unknown. Spinal CSF leakages have been theorized to be associated with the development of intracranial hypotension. The most common treatment is
* Corresponding author at: Department of Hygiene and Public Health, Teikyo University School of Medicine, 2-11-1 Kaga Itabashi, Tokyo 173-8605, Japan. Tel.: +81 0 339 643 615; fax: +81 0 339 641 058. E-mail address: [email protected] (K. Ohwaki).
the injection of autologous blood into the epidural space, or epidural blood patch. Neither a gold standard nor diagnostic criteria have been established to define intracranial hypotension [1]. Although many studies have described various features of neuroimaging tests that have been observed in patients with intracranial hypotension [2–11], few have examined their validity and reliability. Since spinal CSF leaks are thought to cause intracranial hypotension, detecting CSF leaks should be useful in making an accurate diagnosis. Radionuclide cisternography is particularly useful for identifying CSF leaks and studying the CSF circulation. In fact, cisternography often reveals the approximate site of the leak by demonstrating radioactivity across the dural sac [2,3,5,6,8,12–15]. Magnetic resonance imaging (MRI) has also been reported to be of great help in the diagnosis of intracranial hypotension. Typical
http://dx.doi.org/10.1016/j.advms.2013.12.007 1896-1126/ß 2014 Published by Elsevier Urban & Partner Sp. z o.o. on behalf of Medical University of Bialystok.
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
G Model
ADVMS 36 1–4 K. Ohwaki et al. / Advances in Medical Sciences xxx (2014) xxx–xxx
2
34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
MRI findings, such as subdural fluid accumulation, pachymeningeal enhancement, venous engorgement, pituitary hyperemia, and a sagging brain, have been reported in intracranial hypotension [1,4–7,9,10,16]. However, such diagnostic abnormalities are not always detected [17,18] and relatively high proportion (20%) of the cases shows no abnormalities [1]. Since those studies were based on relatively small patient series or single cases, the sensitivity of MRI remains to be confirmed. It is essential to investigate the spectrum of abnormalities on MRI that correspond to intracranial hypotension. In addition, the associations between MRI findings and CSF leaks detected by radionuclide cisternography should be evaluated. Therefore, this study investigated the incidence of CSF leaks by radionuclide cisternography and abnormal MRI findings that are commonly reported in intracranial hypotension. In addition, we evaluated the association between these two techniques in the accurate diagnosis of intracranial hypotension.
51
2. Patients and methods
52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97
The study protocol was approved by the internal review board of Teikyo University School of Medicine. We retrospectively assessed 250 patients who presented with suspected intracranial hypotension and underwent subsequent radionuclide cisternography between January 2003 and August 2006. Intracranial hypotension was suspected when a patient complained of typical orthostatic headaches or had a history of minor trauma and complained about persistent headaches, cranial nerve dysfunction, autonomic dysfunction, or higher brain dysfunction. The patient group consisted of 110 males (44%) and 140 females with an age range of 9–76 (mean 39 12) years. Of these, 200 patients had a history of minor trauma: head injury in 43 patients (17%), whiplash injury in 142 (57%), and other injuries in 15 (6%). Radionuclide cisternography was performed following a lumbar injection of 111In-diethylenetriamine penta-acetic acid. Images were obtained shortly after injection and 2, 4, and 6 h later. Direct signs of tracer leakage into the spinal epidural space are typically observed with the early accumulation of the tracer in the urinary bladder. Therefore, CSF leakage has been defined as direct signs of tracer in the spinal epidural space or early accumulation of the tracer in the urinary bladder, without direct signs of leakage (2 h after injection) [2,3,5,6,8,12–14]. One of the authors (T.N.) reviewed all of the images. All of the patients’ medical records and imaging studies were reviewed. From the 250 patients who underwent radionuclide cisternography, 159 sagittal and 153 coronal images of T2-weighted images (both n = 152) and 101 gadolinium-enhanced T1-weighted images were obtained in our facility. Sagging of the brain was defined as when the tip of the cerebellar tonsil was positioned at or below the level of the foramen magnum line (a line drawn from the inferior tip of the clivus to the osseous base of the posterior lip of the foramen magnum) in a sagittal T2-weighted image. The maximum subdural space in the frontal area in sagittal and coronal T2-weighted images was also measured. The data were anonymized by numerical coding and recorded in a database. In addition to sex and age, history of trauma was recorded, including head, whiplash, or other injuries. We assessed CSF leaks in relation to demographic factors, sagging of the brain, the maximum subdural space present in sagittal and coronal images, and dural enhancement. The differences between patients with and without CSF leaks were examined with the chi-square test for categorical variables and with the t-test or Wilcoxon rank sum test for continuous variables. All analyses were performed using the SAS statistical package (SAS Institute Inc., Cary, NC, USA). The criterion for significance was set at p < 0.05.
3. Results
98
Overall, 186 (74%) patients showed CSF leaks, including direct signs of tracer leakage into the spinal epidural space in 154 patients (62%) and early accumulation of the tracer in the urinary bladder (without direct signs of leak) in 32 patients (13%). Among the 159 patients for whom sagittal images were obtained, sagging of the brain (Fig. 1a) was observed in 21
99 100 101 102 103 104
Fig. 1. T2-weighted magnetic resonance image in the sagittal view shows brain sagging, or downward tonsillar displacement (a) and T1-weighted image in the coronal view with contrast medium shows diffuse pachymeningeal enhancement (b).
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
G Model
ADVMS 36 1–4 K. Ohwaki et al. / Advances in Medical Sciences xxx (2014) xxx–xxx
3
Table 1
Q2 Relationship between CSF leaks as detected by radionuclide cisternography and magnetic resonance imaging.
Female sex Age, years, mean (SD) Trauma Head injury Whiplash injury Other reasons
Sagging of the brain Maximum subdural space in sagittal image, mm, median (interquartile range)
Maximum subdural space in coronal image, mm, median (interquartile range)
Dural enhancement
Patients with CSF leaks n = 186
Patients without CSF leaks n = 64
p value
106 (57) 38 12
34 (53) 42 11
0.59 0.03 0.54
31 (17) 109 (59) 9 (5)
12 (19) 33 (52) 6 (9)
Patients with CSF leaks n = 119
Patients without CSF leaks n = 40
p value
17 (14) 4.1 (3.0–5.7)
4 (10) 3.7 (2.8–4.8)
0.49 0.18
Patients with CSF leaks n = 114
Patients without CSF leaks n = 39
p value
2.8 (1.6–4.1)
2.5 (1.5–3.6)
0.53
Patients with CSF leaks n = 78
Patients without CSF leaks n = 23
p value
1 (1)
0 (0)
1.00
Values are n (%) unless otherwise stated. CSF – cerebrospinal fluid.
105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121
(13%). In most of the patients (n = 14), the tip of the cerebellar tonsil was at the level of the foramen magnum line. The median (interquartile range) maximum subdural space in either the sagittal (n = 159) or coronal (n = 153) image was 4.0 (2.9–5.6) mm and 2.7 (1.6–4.0) mm, respectively. Table 1 illustrates the relationship between clinical factors, including MRI findings, and CSF leaks as detected by radionuclide cisternography. Patients with CSF leaks were younger than those without CSF leaks and the difference appeared statistically significant (p = 0.03). A sagging brain was not associated with CSF leaks (14% vs. 10%;p = 0.49). Compared to patients without CSF leaks, those who experienced CSF leaks tended to have a larger maximum subdural space in the sagittal (3.7 vs. 4.1 mm) or coronal (2.5 vs. 2.8 mm) image; however, the differences were not statistically significant (p = 0.18 and p = 0.53, respectively). Dural enhancement (Fig. 1b) was observed only in one patient, who experienced CSF leaks as detected by radionuclide cisternography (1.3%).
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4. Discussion
123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144
This study investigated the incidence of CSF leaks detected by radionuclide cisternography and abnormal MRI findings, and determined the relationship between the two techniques in the accurate diagnosis of patients suspected of having intracranial hypotension. Overall, 74% of the patients examined showed CSF leaks on radionuclide cisternography, while dural enhancement was identified with MRI in one patient only and sagging of the brain in 13% of the patients. We found no significant associations between radionuclide cisternography and MRI findings. The MRI findings reported in previous studies do not appear to be associated with CSF leaks detected by radionuclide cisternography. Various clinical and diagnostic criteria of intracranial hypotension have been described [2–11,16]. A wide variety of MRI features have been reported among patients with intracranial hypotension; however, such findings have been obtained primarily from small case series. The MRI findings have yet to be investigated in a large cohort. The definitive profile of MRI abnormalities for an accurate diagnosis remains to be established. Since no observation could potentially define intracranial hypotension, its objective nature is questionable. In our study, for example, only 17 of 119 (14%) patients with CSF leaks detected by radionuclide cisternography also had a sagging brain.
Radionuclide cisternography is considered to be the most valid technique for the diagnosis of intracranial hypotension because it unequivocally locates the leak. In addition, typical findings include an early accumulation of tracer in the kidneys and bladder, slow ascent along the spinal axis, and a paucity of activity over the cerebral convexities [2,5,6,8,12–14]. In most cases, radionuclide cisternography shows the early accumulation of tracer in the kidneys and bladder. These findings suggest unusually rapid uptake of the tracer into the bloodstream via the extensive epidural venous plexus [8,13,14]. The early accumulation of tracer in the bladder may be associated with lumbar puncture [19]. Even when we excluded patients with early accumulation of tracer in the bladder (n = 32) from our analyses, the associations between CFS leaks and MRI findings were not significant: sagging brain (12% vs. 10%; p = 0.22), and maximum subdural space in sagittal (4.2 vs. 3.7 mm; p = 0.19) or coronal (2.8 vs. 2.5 mm; p = 0.50) images. In our study, a sagging brain and dural enhancement were observed in 13% and only in one patient, respectively. The discrepancy between the previous studies and our studies may be, in part, due to the selection methods of patients. In previous studies, MRI was usually used to diagnose intracranial hypotension. We performed radionuclide cisternography in a positive manner, independent of MRI findings. Therefore, in our study a relatively small portion of the patients may have shown abnormalities on MRI. The first treatment of intracranial hypotension is bed rest and hydration. When such conservative treatments fail, epidural blood patch is the procedure of choice. Improvement of symptoms after epidural blood patch is included in the recent diagnostic criteria [20]. Given that epidural blood patch is an invasive procedure, however, epidural blood patch should be done after diagnosis. More valid neuroimaging techniques and particular findings need to be identified in order to diagnose intracranial hypotension accurately. This study has several limitations that should be noted. The findings of radionuclide cisternography and MRI were assessed by a single author. Some misclassification of the interpretation of the findings may have occurred. If an unintentional bias associated the MRI findings with radionuclide cisternography findings, we would have found associations between the two techniques; however, we did not find any associations. Data on MRI findings were not obtained from all of the patients in our cohort. Although MRI preceded radionuclide cisternography in most of the patients, we
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
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included only findings obtained in our hospital to guarantee the same standard of MRI. We acknowledge that the finding of no significant difference in a study with a small population does not prove any association. However, dural enhancement was observed only in one of our patients with CSF leaks, and sagging of the brain only in 14% (vs. 10% of patients without CSF leaks). Our findings suggest that MRI findings are not clinically significant for an accurate diagnosis of intracranial hypotension. Finally, this series consisted of patients treated at a single university hospital. Further studies based on larger patient populations are required to demonstrate the stability and generalizability of the findings.
198
5. Conclusions
199 200 201 202 203 204 205 206 207
We investigated the incidence of CSF leaks detected by radionuclide cisternography and abnormal MRI findings, and determined the relationship between the two techniques in the accurate diagnosis of patients suspected of having intracranial hypotension. Our study, which included a relatively large population, did not find any association between the findings of two techniques. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately.
208
Financial disclosure
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The authors have no financing to disclose. Conflict of interests The authors declare no conflict of interests. References [1] Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006;295(May (19)):2286–96. [2] Kong DS, Park K, Nam do H, Lee JI, Kim JS, Eoh W, et al. Clinical features and long-term results of spontaneous intracranial hypotension. Neurosurgery 2005;57(July (1)):91–6.
[3] Miyazawa K, Shiga Y, Hasegawa T, Endoh M, Okita N, Higano S, et al. CSF hypovolemia vs intracranial hypotension in ‘‘spontaneous intracranial hypotension syndrome’’. Neurology 2003;60(March (6)):941–7. [4] Schievink WI, Maya MM, Louy C. Cranial MRI predicts outcome of spontaneous intracranial hypotension. Neurology 2005;64(April (7)):1282–4. [5] Chung SJ, Kim JS, Lee MC. Syndrome of cerebral spinal fluid hypovolemia: clinical and imaging features and outcome. Neurology 2000;55(November (9)):1321–7. [6] Schievink WI, Meyer FB, Atkinson JL, Mokri B. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. J Neurosurg 1996;84(April (4)):598–605. [7] Mokri B, Piepgras DG, Miller GM. Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium enhancement. Mayo Clin Proc 1997;72(May (5)):400–13. [8] Molins A, Alvarez J, Sumalla J, Titus F, Codina A. Cisternographic pattern of spontaneous liquoral hypotension. Cephalalgia 1990;10(April (2)):59–65. [9] Tosaka M, Sato N, Fujimaki H, Takahashi A, Saito N. Wave-like appearance of diffuse pachymeningeal enhancement associated with intracranial hypotension. Neuroradiology 2005;47(May (5)):362–7. [10] Forghani R, Farb RI. Diagnosis and temporal evolution of signs of intracranial hypotension on MRI of the brain. Neuroradiology 2008;50(December (12)): 1025–34. [11] Farb RI, Forghani R, Lee SK, Mikulis DJ, Agid R. The venous distension sign: a diagnostic sign of intracranial hypotension at MR imaging of the brain. AJNR Am J Neuroradiol 2007;28(September (8)):1489–93. [12] Moriyama E, Ogawa T, Nishida A, Ishikawa S, Beck H. Quantitative analysis of radioisotope cisternography in the diagnosis of intracranial hypotension. J Neurosurg 2004;101(September (3)):421–6. [13] Ali SA, Cesani F, Zuckermann JA, Nusynowitz ML, Chaljub G. Spinal-cerebrospinal fluid leak demonstrated by radiopharmaceutical cisternography. Clin Nucl Med 1998;23(March (3)):152–5. [14] Rando TA, Fishman RA. Spontaneous intracranial hypotension: report of two cases and review of the literature. Neurology 1992;42(March (3 Pt 1)):481–7. [15] Yoon SH, Chung YS, Yoon BW, Kim JE, Paek SH, Kim DG. Clinical experiences with spontaneous intracranial hypotension: a proposal of a diagnostic approach and treatment. Clin Neurol Neurosurg 2011;113(June (5)):373–9. [16] Schievink WI, Maya MM, Louy C, Moser FG, Tourje J. Diagnostic criteria for spontaneous spinal CSF leaks and intracranial hypotension. AJNR Am J Neuroradiol 2008;29(May (5)):853–6. [17] Schievink WI, Tourje J. Intracranial hypotension without meningeal enhancement on magnetic resonance imaging. Case report. J Neurosurg 2000;92(March (3)):475–7. [18] Schoffer KL, Benstead TJ, Grant I. Spontaneous intracranial hypotension in the absence of magnetic resonance imaging abnormalities. Can J Neurol Sci 2002;29(August (3)):253–7. [19] Halac¸ M, Albayram S, Ceyhan E, Ozer H, Dogan I, Sager S, et al. Is early bladder activity in radionuclide cisternography an indirect sign of spontaneous intracranial hypotension or sequence of lumbar puncture? Clin Nucl Med 2007;32(November (11)):850–3. [20] Schievink WI, Dodick DW, Mokri B, Silberstein S, Bousser MG, Goadsby PJ. Diagnostic criteria for headache due to spontaneous intracranial hypotension: a perspective. Headache 2011;51(October (9)):1442–4.
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
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ADVMS 36 1–4 Advances in Medical Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Advances in Medical Sciences journal homepage: www.elsevier.com/locate/advms 1 2 3 4 5 6 7 8 9
Original Research Article
Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension Ohwaki a,*, Eiji Yano a, Takayuki Shinohara b, Takehiro Watanabe b, Akiko Ogawa b, Norio Fujii b, Tadayoshi Nakagomi b
Q1 Kazuhiro
a b
Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 21 February 2013 Accepted 19 December 2013 Available online xxx
Purpose: Although many studies have described various features of neuroimaging tests associated with intracranial hypotension, few have examined their validity and reliability. We evaluated the association between CSF leaks detected by radionuclide cisternography and abnormal MRI findings in the accurate diagnosis of intracranial hypotension. Patients/methods: We retrospectively assessed 250 patients who were suspected of intracranial hypotension and underwent subsequent radionuclide cisternography. We obtained 159 sagittal and 153 coronal T2-weighted MRI images and 101 gadolinium-enhanced T1-weighted MRI images. We assessed the CSF leaks in relation to a sagging brain, the maximum subdural space in sagittal and coronal images, and dural enhancement. Results: Overall, 186 (74%) patients showed CSF leaks on radionuclide cisternography. A sagging brain was observed in 21 (13%) of the 159 patients with sagittal MRIs. A sagging brain was not associated with CSF leaks (14% vs. 10%; p = 0.49). Compared to patients without CSF leaks, those with CSF leaks tended to have a larger maximum subdural space in both the sagittal (3.7 vs. 4.1 mm) and coronal (2.5 vs. 2.8 mm) images; however, the differences were not significant (p = 0.18 and p = 0.53, respectively). Dural enhancement was observed only in one patient, who presented with CSF leaks on radionuclide cisternography. Conclusions: Our study, which included a relatively large population, did not find any association between the findings of radionuclide cisternography and MRI. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately. ß 2014 Published by Elsevier Urban & Partner Sp. z o.o. on behalf of Medical University of Bialystok.
Keywords: Intracranial hypotension Magnetic resonance imaging Cerebrospinal fluid Radionuclide imaging Headache
10 11
1. Introduction
12 13 14 15 16 17 18
Once considered an exceedingly rare disorder, intracranial hypotension has recently been identified as an important cause of persistent headaches. It is characterized by orthostatic headache and low cerebrospinal fluid (CSF) pressure. However, the nature of intracranial hypotension remains largely unknown. Spinal CSF leakages have been theorized to be associated with the development of intracranial hypotension. The most common treatment is
* Corresponding author at: Department of Hygiene and Public Health, Teikyo University School of Medicine, 2-11-1 Kaga Itabashi, Tokyo 173-8605, Japan. Tel.: +81 0 339 643 615; fax: +81 0 339 641 058. E-mail address: [email protected] (K. Ohwaki).
the injection of autologous blood into the epidural space, or epidural blood patch. Neither a gold standard nor diagnostic criteria have been established to define intracranial hypotension [1]. Although many studies have described various features of neuroimaging tests that have been observed in patients with intracranial hypotension [2–11], few have examined their validity and reliability. Since spinal CSF leaks are thought to cause intracranial hypotension, detecting CSF leaks should be useful in making an accurate diagnosis. Radionuclide cisternography is particularly useful for identifying CSF leaks and studying the CSF circulation. In fact, cisternography often reveals the approximate site of the leak by demonstrating radioactivity across the dural sac [2,3,5,6,8,12–15]. Magnetic resonance imaging (MRI) has also been reported to be of great help in the diagnosis of intracranial hypotension. Typical
http://dx.doi.org/10.1016/j.advms.2013.12.007 1896-1126/ß 2014 Published by Elsevier Urban & Partner Sp. z o.o. on behalf of Medical University of Bialystok.
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
G Model
ADVMS 36 1–4 K. Ohwaki et al. / Advances in Medical Sciences xxx (2014) xxx–xxx
2
34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
MRI findings, such as subdural fluid accumulation, pachymeningeal enhancement, venous engorgement, pituitary hyperemia, and a sagging brain, have been reported in intracranial hypotension [1,4–7,9,10,16]. However, such diagnostic abnormalities are not always detected [17,18] and relatively high proportion (20%) of the cases shows no abnormalities [1]. Since those studies were based on relatively small patient series or single cases, the sensitivity of MRI remains to be confirmed. It is essential to investigate the spectrum of abnormalities on MRI that correspond to intracranial hypotension. In addition, the associations between MRI findings and CSF leaks detected by radionuclide cisternography should be evaluated. Therefore, this study investigated the incidence of CSF leaks by radionuclide cisternography and abnormal MRI findings that are commonly reported in intracranial hypotension. In addition, we evaluated the association between these two techniques in the accurate diagnosis of intracranial hypotension.
51
2. Patients and methods
52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97
The study protocol was approved by the internal review board of Teikyo University School of Medicine. We retrospectively assessed 250 patients who presented with suspected intracranial hypotension and underwent subsequent radionuclide cisternography between January 2003 and August 2006. Intracranial hypotension was suspected when a patient complained of typical orthostatic headaches or had a history of minor trauma and complained about persistent headaches, cranial nerve dysfunction, autonomic dysfunction, or higher brain dysfunction. The patient group consisted of 110 males (44%) and 140 females with an age range of 9–76 (mean 39 12) years. Of these, 200 patients had a history of minor trauma: head injury in 43 patients (17%), whiplash injury in 142 (57%), and other injuries in 15 (6%). Radionuclide cisternography was performed following a lumbar injection of 111In-diethylenetriamine penta-acetic acid. Images were obtained shortly after injection and 2, 4, and 6 h later. Direct signs of tracer leakage into the spinal epidural space are typically observed with the early accumulation of the tracer in the urinary bladder. Therefore, CSF leakage has been defined as direct signs of tracer in the spinal epidural space or early accumulation of the tracer in the urinary bladder, without direct signs of leakage (2 h after injection) [2,3,5,6,8,12–14]. One of the authors (T.N.) reviewed all of the images. All of the patients’ medical records and imaging studies were reviewed. From the 250 patients who underwent radionuclide cisternography, 159 sagittal and 153 coronal images of T2-weighted images (both n = 152) and 101 gadolinium-enhanced T1-weighted images were obtained in our facility. Sagging of the brain was defined as when the tip of the cerebellar tonsil was positioned at or below the level of the foramen magnum line (a line drawn from the inferior tip of the clivus to the osseous base of the posterior lip of the foramen magnum) in a sagittal T2-weighted image. The maximum subdural space in the frontal area in sagittal and coronal T2-weighted images was also measured. The data were anonymized by numerical coding and recorded in a database. In addition to sex and age, history of trauma was recorded, including head, whiplash, or other injuries. We assessed CSF leaks in relation to demographic factors, sagging of the brain, the maximum subdural space present in sagittal and coronal images, and dural enhancement. The differences between patients with and without CSF leaks were examined with the chi-square test for categorical variables and with the t-test or Wilcoxon rank sum test for continuous variables. All analyses were performed using the SAS statistical package (SAS Institute Inc., Cary, NC, USA). The criterion for significance was set at p < 0.05.
3. Results
98
Overall, 186 (74%) patients showed CSF leaks, including direct signs of tracer leakage into the spinal epidural space in 154 patients (62%) and early accumulation of the tracer in the urinary bladder (without direct signs of leak) in 32 patients (13%). Among the 159 patients for whom sagittal images were obtained, sagging of the brain (Fig. 1a) was observed in 21
99 100 101 102 103 104
Fig. 1. T2-weighted magnetic resonance image in the sagittal view shows brain sagging, or downward tonsillar displacement (a) and T1-weighted image in the coronal view with contrast medium shows diffuse pachymeningeal enhancement (b).
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
G Model
ADVMS 36 1–4 K. Ohwaki et al. / Advances in Medical Sciences xxx (2014) xxx–xxx
3
Table 1
Q2 Relationship between CSF leaks as detected by radionuclide cisternography and magnetic resonance imaging.
Female sex Age, years, mean (SD) Trauma Head injury Whiplash injury Other reasons
Sagging of the brain Maximum subdural space in sagittal image, mm, median (interquartile range)
Maximum subdural space in coronal image, mm, median (interquartile range)
Dural enhancement
Patients with CSF leaks n = 186
Patients without CSF leaks n = 64
p value
106 (57) 38 12
34 (53) 42 11
0.59 0.03 0.54
31 (17) 109 (59) 9 (5)
12 (19) 33 (52) 6 (9)
Patients with CSF leaks n = 119
Patients without CSF leaks n = 40
p value
17 (14) 4.1 (3.0–5.7)
4 (10) 3.7 (2.8–4.8)
0.49 0.18
Patients with CSF leaks n = 114
Patients without CSF leaks n = 39
p value
2.8 (1.6–4.1)
2.5 (1.5–3.6)
0.53
Patients with CSF leaks n = 78
Patients without CSF leaks n = 23
p value
1 (1)
0 (0)
1.00
Values are n (%) unless otherwise stated. CSF – cerebrospinal fluid.
105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121
(13%). In most of the patients (n = 14), the tip of the cerebellar tonsil was at the level of the foramen magnum line. The median (interquartile range) maximum subdural space in either the sagittal (n = 159) or coronal (n = 153) image was 4.0 (2.9–5.6) mm and 2.7 (1.6–4.0) mm, respectively. Table 1 illustrates the relationship between clinical factors, including MRI findings, and CSF leaks as detected by radionuclide cisternography. Patients with CSF leaks were younger than those without CSF leaks and the difference appeared statistically significant (p = 0.03). A sagging brain was not associated with CSF leaks (14% vs. 10%;p = 0.49). Compared to patients without CSF leaks, those who experienced CSF leaks tended to have a larger maximum subdural space in the sagittal (3.7 vs. 4.1 mm) or coronal (2.5 vs. 2.8 mm) image; however, the differences were not statistically significant (p = 0.18 and p = 0.53, respectively). Dural enhancement (Fig. 1b) was observed only in one patient, who experienced CSF leaks as detected by radionuclide cisternography (1.3%).
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4. Discussion
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This study investigated the incidence of CSF leaks detected by radionuclide cisternography and abnormal MRI findings, and determined the relationship between the two techniques in the accurate diagnosis of patients suspected of having intracranial hypotension. Overall, 74% of the patients examined showed CSF leaks on radionuclide cisternography, while dural enhancement was identified with MRI in one patient only and sagging of the brain in 13% of the patients. We found no significant associations between radionuclide cisternography and MRI findings. The MRI findings reported in previous studies do not appear to be associated with CSF leaks detected by radionuclide cisternography. Various clinical and diagnostic criteria of intracranial hypotension have been described [2–11,16]. A wide variety of MRI features have been reported among patients with intracranial hypotension; however, such findings have been obtained primarily from small case series. The MRI findings have yet to be investigated in a large cohort. The definitive profile of MRI abnormalities for an accurate diagnosis remains to be established. Since no observation could potentially define intracranial hypotension, its objective nature is questionable. In our study, for example, only 17 of 119 (14%) patients with CSF leaks detected by radionuclide cisternography also had a sagging brain.
Radionuclide cisternography is considered to be the most valid technique for the diagnosis of intracranial hypotension because it unequivocally locates the leak. In addition, typical findings include an early accumulation of tracer in the kidneys and bladder, slow ascent along the spinal axis, and a paucity of activity over the cerebral convexities [2,5,6,8,12–14]. In most cases, radionuclide cisternography shows the early accumulation of tracer in the kidneys and bladder. These findings suggest unusually rapid uptake of the tracer into the bloodstream via the extensive epidural venous plexus [8,13,14]. The early accumulation of tracer in the bladder may be associated with lumbar puncture [19]. Even when we excluded patients with early accumulation of tracer in the bladder (n = 32) from our analyses, the associations between CFS leaks and MRI findings were not significant: sagging brain (12% vs. 10%; p = 0.22), and maximum subdural space in sagittal (4.2 vs. 3.7 mm; p = 0.19) or coronal (2.8 vs. 2.5 mm; p = 0.50) images. In our study, a sagging brain and dural enhancement were observed in 13% and only in one patient, respectively. The discrepancy between the previous studies and our studies may be, in part, due to the selection methods of patients. In previous studies, MRI was usually used to diagnose intracranial hypotension. We performed radionuclide cisternography in a positive manner, independent of MRI findings. Therefore, in our study a relatively small portion of the patients may have shown abnormalities on MRI. The first treatment of intracranial hypotension is bed rest and hydration. When such conservative treatments fail, epidural blood patch is the procedure of choice. Improvement of symptoms after epidural blood patch is included in the recent diagnostic criteria [20]. Given that epidural blood patch is an invasive procedure, however, epidural blood patch should be done after diagnosis. More valid neuroimaging techniques and particular findings need to be identified in order to diagnose intracranial hypotension accurately. This study has several limitations that should be noted. The findings of radionuclide cisternography and MRI were assessed by a single author. Some misclassification of the interpretation of the findings may have occurred. If an unintentional bias associated the MRI findings with radionuclide cisternography findings, we would have found associations between the two techniques; however, we did not find any associations. Data on MRI findings were not obtained from all of the patients in our cohort. Although MRI preceded radionuclide cisternography in most of the patients, we
Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
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included only findings obtained in our hospital to guarantee the same standard of MRI. We acknowledge that the finding of no significant difference in a study with a small population does not prove any association. However, dural enhancement was observed only in one of our patients with CSF leaks, and sagging of the brain only in 14% (vs. 10% of patients without CSF leaks). Our findings suggest that MRI findings are not clinically significant for an accurate diagnosis of intracranial hypotension. Finally, this series consisted of patients treated at a single university hospital. Further studies based on larger patient populations are required to demonstrate the stability and generalizability of the findings.
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5. Conclusions
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We investigated the incidence of CSF leaks detected by radionuclide cisternography and abnormal MRI findings, and determined the relationship between the two techniques in the accurate diagnosis of patients suspected of having intracranial hypotension. Our study, which included a relatively large population, did not find any association between the findings of two techniques. Future research should focus on identifying more valid neuroimaging findings to diagnose intracranial hypotension accurately.
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Financial disclosure
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The authors have no financing to disclose. Conflict of interests The authors declare no conflict of interests. References [1] Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006;295(May (19)):2286–96. [2] Kong DS, Park K, Nam do H, Lee JI, Kim JS, Eoh W, et al. Clinical features and long-term results of spontaneous intracranial hypotension. Neurosurgery 2005;57(July (1)):91–6.
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Please cite this article in press as: Ohwaki K, et al. Spinal cerebrospinal fluid leaks detected by radionuclide cisternography and magnetic resonance imaging in patients suspected of intracranial hypotension. Adv Med Sci (2014), http://dx.doi.org/10.1016/ j.advms.2013.12.007
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