Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure

Discussion

Spinal CSF leaks in SIH, which can be detected by myelography in some cases, cause loss of CSF volume, which some investigators believe results in the changes seen on brain imaging.^10,11 Given the known relationship between pressure and volume in a closed system, one would expect that these imaging signs of SIH would also be correlated with low CSF pressure, another common finding in SIH. To the contrary, however, our investigation shows that while the presence of ≥1 brain imaging sign is relatively common in patients with SIH, there is weak correlation between individual brain or myelographic imaging signs and a patient's CSF pressure. As a result, discordance between the expected imaging signs and the finding of low CSF pressure is routinely encountered.

This discordance indicates that the imaging findings associated with SIH are not uniformly accompanied by a low-pressure state. Furthermore, it reinforces the need to pursue the diagnosis by using a combination of CSF pressure measurement, brain imaging, and spinal imaging rather than any single test when the diagnosis is suspected.

Our investigation is not the first to describe the variability of CSF pressure and imaging findings in patients with SIH.¹² Mokri⁵ previously reported a case series of patients with SIH who demonstrated discordant pressure and imaging and suggested that decreased CSF volume rather than decreased pressure was a more appropriate conception of the disease. Since then, other authors have made similar observations, though predominantly in single case reports or small case series.^13⇓–15 Our data, however, confirm that this variability is common in a large proportion of patients with the disease, rather than in a small subset.

Despite previous reports on this discordance between symptoms and CSF pressure, the concept that low CSF pressure (ie, ≤6 cm H₂O) is the fundamental pathology underpinning SIH remains entrenched in both the literature and professional societies. For example, the International Classification of Headache Disorders, 3rd edition² published in 2013 classifies SIH as “headache attributed to low cerebrospinal fluid pressure.” Similarly, a review published in 2015 states that “a decrease in CSF pressure defines spontaneous intracranial hypotension.”¹⁶ In our experience, these definitions lead to confusion among clinicians seeking to evaluate patients for the condition, often leading to the misconception that CSF pressure measurement alone is sufficient to diagnose or exclude SIH.

Having established that discordance between imaging (which likely principally reflects CSF volume) and CSF pressure is common in SIH, one must next consider why this seemingly paradoxical state occurs, because a loss in CSF volume would be expected to result in decreased CSF pressure. To answer this question, it is useful to briefly consider normal CSF physiology. In the steady-state, CSF pressure is greater than systemic venous pressure, a fact that permits reabsorption of CSF at the level of the arachnoid granulations.¹⁷ Maintenance of this steady-state CSF pressure occurs via balancing of CSF production and absorption.¹⁷ Thus, if CSF volume decreases and CSF pressure falls below venous pressure, CSF absorption will decrease; this decrease allows CSF volume to re-accumulate and restore normal CSF pressure, a process termed “dynamic equilibrium.”¹⁸ It is possible, however, to disrupt the homeostatic mechanisms that maintain a constant CSF pressure if the buffering capacity of the system is overwhelmed.¹⁷

On the basis of our data, it is clear that some patients with CSF leaks are able to maintain the steady-state CSF pressure while others are not, though the ability to maintain the CSF pressure does not necessarily prevent headache in these patients. Furthermore, it seems that this ability to maintain CSF pressure is not solely a function of a slower rate of CSF leakage because we observed no difference in CSF pressures between patients who had evidence of a high-flow CSF leak and those with no leak seen. These observations suggest 2 conclusions: First, that headache in patients with SIH is not primarily determined by low CSF pressure; and second, compensatory mechanisms exist in some individuals that help maintain CSF pressure despite active CSF volume loss.

One potential compensatory mechanism that may vary from person to person is compliance of the thecal sac, which may be influenced by body habitus or dilation of epidural veins. For example, in a recent investigation, Tain et al¹⁹ demonstrated that the compliance of the spinal canal was less in patients with obesity with idiopathic intracranial hypertension (pseudotumor cerebri) than in healthy controls, noting that MR imaging of the thecal sac showed a reduced cross-sectional area of the spinal CSF spaces in these patients.^19,20 In SIH, dilation of the epidural venous plexus has been observed in some cases,²¹ which would reduce cross-sectional area of the spinal canal, thereby compensating for CSF volume loss and increasing CSF pressure, in a manner analogous to pseudotumor cerebri. Moreover, cervical venous dilation is known to change between supine and upright posture in healthy individuals but has been observed to demonstrate person-to-person variability,²² a finding that may be more significant in the setting of orthostatic changes in CSF pressure associated with SIH. These compensatory mechanisms would share in common the ability to, at least partially, preserve the overall volume within the enclosed craniospinal canal, allowing CSF pressure to be maintained despite decreased CSF volume due to a spinal fluid leak. In so doing, these proposed mechanisms would satisfy the requirements of the Monro-Kellie hypothesis.¹¹ Further investigation into what compensatory mechanisms are engaged in the setting of SIH could potentially help elucidate the underlying physiology of the CSF pressure/volume relationship in these patients and could help guide novel therapies.

Our study has limitations. First, it is possible that there is variability in CSF pressure that could decrease the accuracy of any single pressure measurement. Second, it is possible that our location at a tertiary care center could result in referral bias, leading to an atypical cohort of subjects with SIH, though all subjects satisfied established diagnostic criteria for SIH and most patients had not been treated previously at other centers.