Pituitary apoplexy accompanying temporal lobe epilepsy as a complication: case report

Background : Pituitary apoplexy is an acute clinical syndrome caused by infarction and/or hemorrhage of pituitary adenoma, which typically presents with severe headache, visual deterioration, and endocrine abnormalities. However, temporal lobe epileptic seizure has not been viewed as a symptom of pituitary apoplexy in the literature. Case presentation : To elucidate further such a rare complication of temporal lobe epilepsy-like seizure, we describe here the rare clinical manifestations of a 55-year-old previously healthy male with pituitary apoplexy harboring headache, combined palsies involving cranial nerves III to VI, endocrinologic disturbances, and temporal lobe epilepsy-like seizure. In addition, we discuss the temporal lobe epilepsy associated with pituitary adenoma based on the literature. Conclusion : Although further accumulation of clinical data is needed, we would like to emphasize the importance of recognition of temporal lobe epilepsy-like seizure due to pituitary apoplexy, and to suggest that early surgery should be considered as an option in patients displaying such a rare complication.

seizure. In addition, we discuss the temporal lobe epilepsy associated with pituitary adenoma based on the literature. Conclusion : Although further accumulation of clinical data is needed, we would like to emphasize the importance of recognition of temporal lobe epilepsy-like seizure due to pituitary apoplexy, and to suggest that early surgery should be considered as an option in patients displaying such a rare complication.
To elucidate such a rare complication of temporal lobe epilepsy and epileptic seizure further, we describe here the rare clinical manifestations of a 55-year-old male with pituitary apoplexy harboring headache, ocular palsies, hypoesthesia in the second division of the trigeminal nerve, endocrinologic disturbances, and temporal lobe epilepsy-like seizure. In addition, we present a small literature review of temporal lobe epilepsy related to pituitary adenoma.
On the day of admission to our institution, endoscopic transnasal transsphenoidal surgery was performed to remove the mass, which was soft and easy to curette. During the surgery, a low level of spinal fluid leakage was noted, but no subarachnoid hemorrhage was observed. Microscopic examinations of the surgical specimen demonstrated a large area that consisted primarily of coagulative necrosis and hemorrhage. A typical adenoma pattern forming diffuse sheets was still evident in the tumor tissues (Fig. 3). These findings were consistent with pituitary apoplexy.
The patient was discharged from our hospital at 20 days after surgery because he was worried about the possible recurrence of epileptic seizure and hospitalization was extended based on his wishes.  (Fig. 4). His left oculomotor nerve deficits including eye ptosis and pupil dilatation and facial hypesthesia due to trigeminal nerve deficit gradually improved, although his abducens nerve palsy persisted after the surgery. An electroencephalogram at 20 days following surgery showed no epileptiform activity. The patient is receiving corticosteroid replacement therapy and anticonvulsant medication at his request but has had no additional epileptic seizure 8 months after surgery, and continues to be followed up.
It is easy to speculate that the pituitary adenoma, which compresses or infiltrates the inner structure of the temporal lobe due to lateral extension, can induce temporal lobe epileptic seizures. Previously, Elkington in 1968 reported that 6 cases out of 260 pituitary adenomas (2.3%) developed epileptic seizure as a preoperative symptom; details were uncertain, but 4 of the 6 cases were of grand mal, one was of temporal lobe epilepsy, and one was of uncinate fits [6]. Deepak et al. in 2007 indicated that much of the information about pituitary adenoma-related seizures including their exact prevalence, clinical and electrophysiological characteristics, and treatment is inadequate [5]. Even now, such details remain to be fully elucidated.
Epileptic seizures have been observed as a complication of medically treated prolactin-producing 6 macroadenoma. Niwa et al. (Japanese-language paper) reported that treatment with bromocriptine alone for prolactin-producing macroadenomas with lateral extension to the cavernous sinus revealed symptomatic seizures during the medical course in 3 out of 9 cases, although in all cases a rapid decrease of serum prolactin level was recognized and in 8 cases evidence of tumor shrinkage was found on CT and/or MRI. Additionally, a hypointense signal on both T1-and T2-weighted images, consistent with hemosiderin due to intratumoral hemorrhage caused by bromocriptine, was recognized around the residual tumor in 3 cases with seizure. They suggested therefore that hemosiderin deposition within the medial surface of the temporal lobe, following bromocriptine therapy for prolactin-producing macroadenomas with intradural supracavernous extension, could be a trigger of such seizures [16]. Thus, if the hemosiderin remains within the adenoma, no seizures will occur, but if the hemosiderin escapes from the adenoma and comes into contact with the medial aspect of the temporal lobe, it could trigger a seizure attack. Deepak et al. reported that 6 out of 29 patients (5 cases of temporal lobe epilepsy and one presenting with grand mal seizure), diagnosed as having macroprolactinoma, which invades the brain parenchyma, had a history of epilepsy prior to or at pituitary adenoma presentation. However, the remaining 23 patients showed no clinical symptoms suggesting epileptic activity despite the presence of brain infiltration by the adenoma on neuroimaging. All 5 patients with temporal epilepsy experienced an immediate reduction in the occurrence of seizures following initiation of dopamine agonist treatment, which coincided with the fall in their serum prolactin levels but with minimal or no radiologic change in the appearance of their tumors, and additionally it was possible to reduce their dose of anti-epileptic medication due to the anti-epileptogenic function of dopamine agonist [5]. On the other hand, gamma knife surgery can serve as a therapeutic tool for uncontrolled pituitary adenoma, but radiation induced MR changes outside of the radiosurgical target and associated transient increases of seizure rate are well-known side effects of radiosurgery [21]. Schindler et al. reported the first case of radiation-induced changes to the mesial temporal lobe structures and transient symptomatic epileptic seizures as rare sideeffects of gamma knife radiosurgery of the cavernous sinus in residual growth hormone secreting pituitary adenoma. The MR changes of their patient were temporary and a diffuse hyperintensity lesion on T2-weighted images with central enhancement was noted in the medial temporal lobe [21].
In our case, it is inferred that unusual compression (including brain edema due to compression of the parenchyma) elicited temporal lobe epilepsy-like seizure, since no changes have been noted in temporal lobe images. However, follow-up with future imaging, such as of the appearance of hemosiderin deposition within the medial surface of the temporal lobe and/or changes to the mesial temporal lobe structures, will be needed to confirm the epileptogenicity and to predict future seizures in our case.
There is as yet no clear consensus regarding the best option for the management of pituitary apoplexy [1-4, 7-14, 17-20, 23-28]. However, classical pituitary apoplexy represents one of the major medical emergencies, and there is no doubt that immediate fluid administration and replacement with hydrocortisone to achieve hemodynamic stability and to reduce hormone deficiencies are important for saving lives [1-4, 7-14, 17-20, 24-27]. On the other hand, the role of pituitary surgery and the timing of surgical decompression of the pituitary fossa remain topics of debate [1-4, 7-14, 17-20, 24-28]. Hitherto, it has been widely accepted that transsphenoidal surgery can be minimally invasive within the first week and should be considered in the presence of severe visual loss for pituitary apoplexy, and that patients without severe visual loss or consciousness impairment may be treated expectantly by conservative management [1-4, 7-14, 17-20, 23-28]. Temporal lobe epilepsy-like seizure induced by pituitary apoplexy is a rare symptom, and it has not been viewed as a complication in the literature [1-4, 8-14, 17-20, 24-27]. However, recognition and optimal treatment of temporal lobe epilepsy-like seizure as a complication of pituitary apoplexy are important, because patients with epilepsy exhibit a diminished quality of life and a high mortality rate as compared to the general population [21,22], and patients with temporal lobe epilepsy are frequently resistant to antiepileptic medication [15,22]. On the other hand, involvement of epileptogenicity over the time course, e.g. irreversible changes within the temporal lobe due to continuous compression and hemosiderin deposition, should be eliminated. Thus, although further accumulation of clinical data is needed, we would like to suggest that early surgery should be considered as an option in patients with temporal lobe epilepsy-like seizure occurring as a complication of pituitary apoplexy. 8 Abbreviations CT: computed tomography; MRI: magnetic resonance imaging; WBC: white blood cell; Hb: hemoglobin; Ht: hematocrit; PLT: platelet; CRP: carbon reactive protein; Na: sodium; K: potassium; Cl: chlorine; ACTH: adrenocorticotropic hormone.

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All authors have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest, in the subject matter or materials discussed in this case report.

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Authors' contributions
KSh and AY contributed to the concept of the manuscript and drafted the manuscript. HO and SYa

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