Rebound Intracranial Hypertension: A Complication of Epidural Blood Patching for Intracranial Hypotension

DISCUSSION

Although RIH is sparsely reported, in our experience it is not an uncommon complication of epidural blood patching. Although this case series was limited to patients with elevated opening pressure confirmed by lumbar puncture and therefore probably represents a subset of patients with a more severe spectrum of disease, we commonly encounter patients with similar, less severe symptoms after EBP. Although often self-limited and minor, RIH symptoms can at times be severe or persist well beyond the immediate posttreatment period. Lack of familiarity with this complication can result in misdiagnosis, including an incorrect attribution of symptoms to refractory intracranial hypotension.

The lack of more widespread recognition of this condition is probably caused by a superficial similarity of presenting features: headache is the predominant symptom experienced by patients with RIH and patients with intracranial hypotension.⁴ This case series highlights several typical features that are useful for discriminating persistent intracranial hypotension from RIH.

First, patients who have RIH typically describe a change in headache phenotype. In contrast to the headaches of intracranial hypotension, which are commonly occipital in location,⁶ we found that headaches in RIH are most commonly frontal or peri-orbital in location (Fig 1). Additionally, headaches in intracranial hypotension are exacerbated with upright positioning, whereas those associated with RIH are typically worse when recumbent. Some patients report that the headaches associated with RIH are worse in the morning. These symptoms mirror features of those patients with raised intracranial pressure caused by other etiologies.^7,8 Jugular venous outflow is impaired in the recumbent position,⁹ which probably accounts for the worsening of symptoms in some patients with RIH while lying down. Prolonged recumbent positioning at night may contribute to morning headaches, though other proposed mechanisms such as a rise in pCO₂ at night, decreased CSF reabsorption, and increased CSF production modulated by chemical factors such as melatonin, for example, may also play a role.^7,10 By contrast, headaches more prominent in the later part of the day are seen in some patients with intracranial hypotension.¹¹

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Fig 1.

A, Patients presenting with intracranial hypotension most commonly – although not exclusively – complain of headaches in the occipital region. B, Patients who develop rebound intracranial hypertension often have a change in headache location, most commonly having headaches in a frontal, peri-orbital, or retro-orbital location.

Second, patients with acute RIH frequently have nausea, vomiting, and blurred vision, which are symptoms commonly found with elevated intracranial pressure. Whereas mild manifestations of these symptoms can occasionally be present at presentation in patients with intracranial hypotension, severe or continuous nausea, vomiting, and blurred vision are not common with low CSF pressure. The development of such symptoms immediately after blood patching should therefore raise suspicion for RIH.

Third, symptoms often develop in close proximity to the time of blood patching. Onset within 24–48 hours of treatment is common, and patients should be monitored most closely during this time period. In our series, onset even within several hours of EBP was not rare. In some cases, patients may even begin to have symptoms during the patching procedure itself while still on the procedure table. Nevertheless, not all patients in our series developed symptoms acutely, and a more delayed onset of symptoms should therefore not exclude the possibility of RIH. In our experience, patients who have development of symptoms over a more prolonged time period generally complain of less severe symptoms than those who have RIH more acutely, though the overall course of their symptoms may be more protracted.

Literature reports of RIH have been limited, with only 8 cases previously described, to our knowledge. The largest previous case series by Mokri⁴ reported 4 patients. Three of those patients had CSF pressure confirmed by lumbar puncture; the other patient was diagnosed by the presence of papilledema. Symptom onset in that series ranged from 1 week to 9 months. Other authors have reported cases of RIH in which symptom onset was more rapid (ranging from immediate to 3 days).^12⇓–14 A single case report described a much more delayed onset of symptoms, occurring 2 years after blood patching.¹⁵ CSF pressure measurements in these series, when measured, ranged from 20–28 cm H₂O. In general, the onset of symptoms in our series was more rapid, with a median time to onset of symptoms of 1 day, and the degree of CSF pressure elevation more severe, with an opening pressure of >25 cm H₂O in 66% of patients. This may be caused in part by sampling bias; patients in our series only underwent lumbar puncture if symptoms were severe, whereas many patients clinically suspected of having mild RIH were treated empirically without a confirmatory lumbar puncture. Thus, patients with milder CSF pressure elevations and/or more gradual symptom onset would not have been likely to be included in this investigation. We used 20 cm H₂O as the threshold for inclusion both because it replicates the criteria of prior reports of the condition and because it is a generally accepted upper limit of normal for CSF pressure in nonobese patients.¹⁶ It is possible, however, that the relative change in CSF pressure contributes to the development of symptoms independent of the absolute CSF pressure.

The mechanism behind the development of RIH is unknown. One potential explanation could be the immediate displacement of CSF from the enclosed confines of the spinal canal caused by the addition of patching material in the epidural space, resulting in increased pressure. Although this mechanism probably exists to some degree in all patients undergoing epidural patching, the degree of pressure increase caused by this mechanism would be expected to be proportional to the volume of patching material used; this was not always seen in our series. For example, 3 patients in our series had development of RIH despite the use of <10 mL patching material, and yet many other patients who receive EBP by use of volumes of 20–30 mL or more do not have RIH. An additional mechanistic possibility could be considered: physiologic mechanisms are engaged in patients with intracranial hypotension to compensate for decreased CSF volume, such as distention of venous structures in the head (as demonstrated by the “venous distention sign”) or in the cervical spinal canal.^5,17 When CSF volume is acutely returned to normal, failure of these compensatory mechanisms to immediately reverse could result in increased intracranial pressure. This explanation does not satisfactorily explain cases of delayed development of RIH, however. Mokri⁴ proposed several other possible mechanisms for RIH including upregulation of CSF production or disrupted CSF reabsorption in the setting of prolonged CSF leak, or return to a preexisting state of (previously unrecognized) idiopathic intracranial hypertension. All of these potential mechanisms, he concluded, were vulnerable to criticism for various reasons. Ultimately, it is possible that multiple different pathways exist that result in raised intracranial pressure and that variable engagement of 1 or more of these pathways may influence the time to onset and severity of symptoms among different patients.

Treatment of RIH in our series consisted of CSF drainage at the time of lumbar puncture, which immediately reduced, and in some cases eliminated, symptoms in all patients. Because the effect of CSF drainage is temporary, most patients were subsequently started on acetazolamide. Acetazolamide is an inhibitor of carbonic anhydrase that decreases CSF production through the inhibition of sodium-hydrogen ion exchange across the choroid plexus.¹⁸ We typically use an oral starting dose of 250 mg twice per day and increase as necessary to control symptoms. Some patients may not be able to tolerate the side effects of acetazolamide, which include paresthesias of the digits, fatigue, and nausea.¹⁹ If patients cannot tolerate acetazolamide, we have used topiramate as an alternative because it also demonstrates carbonic anhydrase inhibitory effect and has been studied as an alternative to acetazolamide in cases of idiopathic intracranial hypertension.^20,21 Acetazolamide should be used cautiously in patients with sulfa allergy, though our experience is that it is well tolerated by most patients with a history of reaction to other sulfa drugs, a finding that agrees with previous reports of the use of acetazolamide in sulfa-allergic patients.²² Other reported strategies for the treatment of RIH include the use of IV glycerol and the need for CSF shunting.^1,13,14 Although we do not routinely admit patients overnight after their procedure, we do explicitly counsel patients on the symptoms that might suggest RIH and follow-up with them frequently by telephone after the procedure, in addition to providing them with emergency contact information should symptoms of RIH develop.

There are several limitations to this investigation. First, by only including patients with an opening pressure of >20 cm H₂O, we probably have excluded some patients with milder, but nonetheless symptomatic, elevations in CSF pressure. These patients may have a relatively increased CSF pressure compared with their pretreatment baseline but with opening pressures that still fall in the normal range. Second, because most patients who undergo epidural blood patching do not undergo routine subsequent CSF pressure evaluation, asymptomatic rises in CSF pressure in some patients could occur. Finally, and perhaps most importantly, we included only patients with symptoms severe enough to warrant repeat lumbar puncture. It is possible that RIH may present with different, less severe, clinical characteristics in patients with less dramatic elevations in CSF pressure.