Cerebral vasospasm as a consequence of pituitary apoplexy: illustrative case

Abstract

BACKGROUND

Cerebral vasospasm is a rare but devastating complication following pituitary apoplexy. Cerebral vasospasm is often associated with subarachnoid hemorrhage (SAH), and early detection is crucial for proper management.

OBSERVATIONS

The authors present a case of cerebral vasospasm after endoscopic endonasal transsphenoid surgery (EETS) in a patient with pituitary apoplexy secondary to pituitary adenoma. They also present a literature review of all similar cases published to date. The patient is a 62-year-old male who presented with headache, nausea, vomiting, weakness, and fatigue. He was diagnosed with pituitary adenoma with hemorrhage, for which he underwent EETS. Pre- and postoperative scans showed SAH. On postoperative day 11, he presented with confusion, aphasia, arm weakness, and unsteady gait. Magnetic resonance imaging and computed tomography scans were consistent with cerebral vasospasm. The patient underwent endovascular treatment of acute intracranial vasospasm and was responsive to intra-arterial milrinone and verapamil infusion of the bilateral internal carotid arteries. There were no further complications.

LESSONS

Cerebral vasospasm is a severe complication that can occur after pituitary apoplexy. It is essential to assess the risk factors linked to the cerebral vasospasm. In addition, a high index of suspicion will allow neurosurgeons to diagnose cerebral vasospasm after EETS early and take the necessary measures to manage it accordingly.

Although cerebral vasospasm is a common life-threatening complication after subarachnoid hemorrhage (SAH), it is rare following pituitary apoplexy.^1,2 This condition is often associated with high morbidity and mortality because it is not usually recognized in a timely manner.³ The pathophysiology of this complication is not yet fully understood, and the most relevant information related to it has been reported in case reports.^4–9 The most common reported risk factor associated with cerebral vasospasm is SAH, although there have been reported cases of cerebral vasospasm without SAH.² In a systematic review, Budnick et al.¹⁰ reported the mortality rate following transsphenoidal (TSS) resection of skull base tumors complicated with vasospasm to be 30%.

Here, we present a case of delayed cerebral vasospasm, a complication of pituitary apoplexy, and a review of eight similar cases published to date.

Illustrative Case

A 62-year-old male, who 2 weeks prior to his presentation had been diagnosed with acute unprovoked pulmonary thromboembolism, which was treated with an anticoagulant, presented with the sudden onset of severe headache, nausea, vomiting, generalized weakness, and fatigue.

His head computed tomography (CT) scan showed a large suprasellar mass consistent with pituitary tumor with hemorrhage consistent with SAH and apoplexy (Fig. 1). Magnetic resonance imaging (MRI) confirmed the presence of a polylobulated sellar/suprasellar homogeneously enhancing mass associated with hemorrhage, which was consistent with pituitary apoplexy (Fig. 2). There was no hydrocephalus. The patient underwent emergency endoscopic endonasal transsphenoid surgery (EETS) for pituitary apoplexy. Results after surgery showed complete removal of the tumor (Fig. 2).

FIG. 1.

Preoperative sagittal (left) and coronal (right) CT scans show a lobulated, hyperdense sellar and suprasellar mass consistent with hemorrhagic pituitary tumor and apoplexy.

FIG. 2.

Preoperative coronal T1-weighted MRI (A) and T1-weighted MRI with gadolinium (B) show a large sellar and suprasellar tumor (26 × 26 × 30 mm). Postoperative coronal (C) and sagittal (D) T1-weighted MRI with gadolinium showed complete resection of the pituitary tumor.

The histopathological test confirmed diagnoses of pituitary adenoma, positive for prolactin by immunohistochemistry, with focal necrosis and hemorrhage.

A cerebrospinal fluid (CSF) leak was reported during surgery, which required an intracranial duraplasty using Duraform. Postoperatively, the patient was managed for pain and diabetes insipidus (DI).

SAH was evident on his postoperative CT head scan. The patient was discharged on postoperative day (POD) 6 with no neurological deficit, but on POD 11, he was readmitted to the hospital for sudden onset of confusion, aphasia, right arm weakness, and unsteady gait. Physical examination showed expressive aphasia (word-finding difficulty and fluency) and overall slowed speech. His MRI head scan showed a subacute infarct in the left basal segment of the left internal carotid artery (ICA), the A1 and proximal A2 segments of the anterior and cerebral arteries. His CT angiography (CTA) scan showed multiple acute ischemic lesions in the left anterior cerebral artery narrowing and middle cerebral artery narrowing territories and mild narrowing of the left carotid siphon consistent with acute vasospasm (Fig. 3). In addition, mild SAH was present in the left suprasellar and sylvian fissure regions. These findings were consistent with cerebral vasospasm.

FIG. 3.

Presentation with cerebral vasospasm. Coronal (A) and sagittal (B) CTA scans showing narrowing of the supraclinoid segment of the left ICA, as well as the A1 and proximal A2 segments of the anterior cerebral artery (ACA). Left ICA arteriogram before (C) and after (D) intra-arterial milrinone and verapamil infusion therapy. Before infusion therapy, there was a severe distal A1/proximal A2 narrowing/vasospasm and moderate to severe spasm in the superior M2 branches, as well as some distal left middle cerebral artery (MCA) branches. After infusion therapy, improved contrast transit time through the distal left MCA territory and its watershed distribution with the left ACA is observed.

The vasospasm initially was managed medically; however, given that there was no improvement after 6 hours, the patient underwent endovascular treatment of acute intracranial vasospasm. Digital subtraction angiography showed a good response to intra-arterial milrinone and verapamil infusion of bilateral ICAs. Serial transcranial Doppler studies showed no evidence of vasospasm after this treatment. There were no other complications during the patient’s hospital stay or after discharge. The 5-week neurosurgery follow-up visit report showed favorable clinical progression with no new clinical symptoms.

Discussion

Observations

EETS resection of a pituitary tumor is often the desired method for pituitary adenoma removal.¹¹ A rare complication that can occur following pituitary apoplexy is cerebral vasospasm.² SAH is the most common risk factor reported in most (84.6%) of the patients who undergo TSS resection.^10,12 Specifically, five (62.5%) out of eight reviewed cases undergoing EETS for pituitary adenoma were associated with postoperative SAH (Table 1).^1,10,13,14

TABLE 1.

Clinical characteristics of cerebral vasospasm cases after pituitary apoplexy

Authors & Year	Age (yrs)/Sex	Presenting Symptoms	Risk Factors	Vasospasm Onset POD	Diagnostic Tests	Treatment	Outcome
Zada et al., 201114	59/M	Acute rt pupillary dilation, blood products in subarachnoid cisterns, acute hydrocephalus, aphasia, bilat leg weakness	Suprasellar extension & SAH & hematoma on POD 2	2	Cerebral angiography, CTA	IA verapamil (3×)	Short-term memory, worse vision, & cognitive dysfunction
	66/M	Acute rt pupillary dilation	Blood products w/in tumor cavity, stable hematoma w/in tumor region, SAH, & suprasellar extension	8	Cerebral angiography, MRA	IA verapamil	Death
Page et al., 20162	44/F	Agitation w/ altered mental status, respiratory distress	Suprasellar extension	19	TCD, CTA	Nimodipine, triple-H therapy	Tracheostomy, gastrostomy, long-term rehabilitation
Eseonu et al., 201612	43/F	Paresthesia (lt), arm weakness (lt), expressive aphasia	Suprasellar extension & tumor bed hemorrhage	12	MRA, TCD	Induced hypertension, euvolemia, phenylephrine, nimodipine	DI followed by complete recovery to neurological baseline
Suero Molina et al., 20191	23/F*	Mouth asymmetry w/ slurred speech, mod weakness of lt arm	Suprasellar extension, SAH, CSF leak	8	Cerebral angiography	IA & IV nimodipine	Complete recovery
Budnick et al., 202010	55/M	Altered mental status & acute lethargy	CSF leak & SAH	7	TCD	IA nicardipine, induced hypertension	Complete recovery
Mansouri et al., 201213	75/M*	Decreased consciousness & rt-sided hemiplegia	SAH, hematoma, suprasellar extension & CSF leak	7	CT perfusion	Induced hypertension & hypervolemia	GOS 3
Chhabra et al., 201915	35/F	Vision loss	Tumor bed hematoma	3	DSA	IA nimodipine	Death
Present study	62/M	Confusion, expressive aphasia, rt arm weakness, & unsteady gait	Suprasellar extension, CSF leak, & SAH	11	TCD	Nimodipine & IA verapamil & milrinone	Complete recovery

DSA = digital subtraction angiography; GOS = Glasgow Outcome Scale score; IA = intra-arterial; IV = intravenous; mod = moderate; TCD = transcranial Doppler.

^*Extended endonasal transsphenoidal approach.

Current research indicated that subarachnoid blood and its components in the cisterns are contributors to cerebral vasospasm.^15–19 Moreover, the presence of free radicals such as the degradation products of hemoglobin (oxyhemoglobin and methemoglobin), as well as the release of vasoactive products from the tumor, was likely to cause vasospasm.^12,20 It was also reported that those products might be responsible for the inflammatory responses that led to decreased nitric oxide levels in the endothelia, which ultimately decreased the blood vessel diameter.^12,21

A postoperative condition that complicates the management of cerebral vasospasm is DI.²² Unlike the vasospasm that develops after aneurysmal SAH, the vasospasm following pituitary apoplexy is more difficult to treat due to the volume management issues associated with DI.^12,22 It is often managed via triple-H therapy (hypertension, hypervolemia, hemodilution).^{10,12,21–23} Induced hypertension has been shown to be an effective option because it increases cerebral blood flow and improves neurological conditions.¹ However, hypervolemia showed no benefits or improvement of clinical outcomes over euvolemia treatment, particularly in cases complicated with DI.^12,24,25 Its use even produced complications such as pulmonary edema as a result of hydrostatic pressure increase inside capillaries, further complicated with fluid buildup.^12,24,25 Finally, hemodilution has not been a very effective treatment either, and recently published studies recommended the use of induced hypertension and euvolemia only.^12,25

In addition to triple-H therapy, intra-arterial vasodilators and angioplasty are commonly used to treat vasospasm following pituitary apoplexy.² Common vasodilator medications include papaverine, verapamil, nimodipine, and milrinone.¹⁰ Endovascular treatment is used when other options fail to produce neurological improvement.²⁵ Moreover, preoperative vascular imaging was recommended for pituitary macroadenoma cases.²² For example, without preoperative vascular imaging in a case of postoperative delayed vasospasm, the use of balloon angioplasty might even be harmful if there is no way to differentiate between an arterial spasm and a hypoplastic artery.²² It has also been reported that the anatomical proximity of the tumor to the hypothalamus should be checked prior to performing the surgery because damaging the hypothalamus could result in the release of chemical products into the CSF, causing catecholamines to activate the sympathetic nervous system and ultimately lead to vasoconstriction.^1,2 Macroadenomas with suprasellar extensions increase this risk because they can be near the hypothalamus and can potentially be damaging.¹ Early detection of cerebral vasospasm requires a high level of suspicion in patients who have recently undergone EETS, especially when hematoma or SAH is involved.^2,10,13

According to the reviewed literature, there are 37 published cases of postoperative cerebral vasospasm following TSS resection of various skull base tumors (pituitary adenomas, craniopharyngiomas, meningiomas, Rathke’s cyst, lymphocytic hypophysitis).^{1,2,4,6–10,12,21,23,26–31} Most of the reviewed cases (25 of 37; 67.6%) were pituitary adenomas complicated postoperatively with cerebral vasospasm (Table 1).^{1,2,4,6–10,12,21,23,26–29} Only 8 out of the 25 reviewed pituitary adenoma cases underwent EETS (Table 1).^{1,2,10,12–15} Half of these patients were female (4 of 8; 50%). The mean age was 50 years (standard deviation ±17, range 23–75).

The EETS resection of pituitary adenoma was complicated with SAH in five (62.5%) out of eight patients (Table 1). Furthermore, most of those who underwent EETS (6 of 8; 75%) presented a suprasellar extension of the pituitary tumor, which was also reported as a risk factor for the cerebral vasospasm.^1,12,21

Our reported patient’s age and cerebral vasospasm presenting symptoms were similar to the published cases. Three of the most common risk factors reported in the published literature (suprasellar extension, CSF leak, and SAH) were also present in our case. Our patient developed cerebral vasospasm on POD 11. This is similar to the average onset of vasospasm following TSS surgery found in reviewed studies. The diagnostic tests and treatment reported in our case and the reviewed cases were similar as well. Finally, our patient fully recovered, as was the case with two other patients who underwent EETS surgery (Table 1).

Last, in the literature, head CTA and brain magnetic resonance angiography (MRA) are most commonly used to detect cerebral vasospasm.¹³ In cases where neither CTA nor MRA indicates the presence of cerebral vasospasm but clinical evidence suggests otherwise (i.e., neurological deterioration), cerebral angiography is recommended in an attempt to rule out cerebral vasospasm, because delayed diagnosis will likely worsen the outcome.^13–15

Management of cerebral vasospasm following pituitary apoplexy has been done mostly via induced hypertension and euvolemia in addition to the administration of vasodilators such as verapamil and nimodipine.^10,12 Endovascular treatment (balloon angioplasty) was used in more severe cases.¹¹

Lessons

We present a case of delayed cerebral vasospasm following pituitary apoplexy. Our literature review identified a minimal number (eight cases) of cerebral vasospasm following pituitary tumor hemorrhage.

Although vasospasm has rarely been reported in the literature, it is essential to note the risk factors associated with this complication. Preoperative and postoperative vascular imaging is recommended for early detection of cerebral vasospasm and consequently better management of this life-threatening complication. However, given the rarity of this complication, more published cases including long-term patient follow-up are needed to provide neurosurgeons with helpful information to understand its pathophysiology better and to identify the most suitable treatment options.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Alsayadi, Moldovan, Alkherayf. Acquisition of data: Ochoa-Sanchez, Alsayadi. Analysis and interpretation of data: Ochoa-Sanchez, Moldovan. Drafting the article: all authors. Critically revising the article: Ochoa-Sanchez, Moldovan, Alkherayf. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Ochoa-Sanchez. Administrative/technical/material support: Ochoa-Sanchez. Study supervision: Ochoa-Sanchez, Moldovan, Alkherayf.