Complete and Immediate Resolution of See-Saw Nystagmus Following Pituitary Macroadenoma Resection: Case Report and Review of the Literature

ABSTRACT

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases.

Introduction

See-saw nystagmus (SSN), first reported by Maddox in 1914,¹ is characterised by the simultaneous elevation and incyclotorsion of one eye with concomitant depression and excyclotorsion of the other eye in an alternating manner.² The mechanism for this form of nystagmus is poorly understood, however it often localises to lesions in the parasellar or midbrain regions. Neuroanatomical pathways implicit in the development of SSN include a unilateral mesodiencephalic lesion occurring in the interstitial nucleus of Cajal (inC) or a medial longitudinal fasciculus (MLF) lesion involving the vertical semicircular canal pathways.^2,3 The pendular variant of SSN more often represents chiasmal involvement in comparison to the jerk variant termed hemi-SSN.^2–4 We report a rare case of pendular SSN that displayed complete resolution in the immediate postoperative course following resection of a pituitary macroadenoma and review the literature of SSN and hemi-SSN presentations over the last 20 years.

We report the presentation, treatment and outcome of a patient diagnosed with SSN. Written informed consent for publication of details presented was obtained from the patient. Additionally, a literature review was conducted to identify all published cases of SSN from 2002 to 2022 and their suspected aetiologies, case presentations, treatments, and outcomes. A manual search was performed using the PubMed search engine for the terms ‘seesaw nystagmus’ OR ‘see-saw nystagmus’ OR ‘pendular seesaw nystagmus’ OR ‘jerk seesaw nystagmus’ OR ‘hemi-seesaw nystagmus’. Publications were identified and included if they presented a novel patient case of SSN. Studies without an English translation were excluded. Other exclusion criteria included articles that discussed pathophysiology without a case presentation, focused on infantile nystagmus, or review articles without case presentations. A total of 29 unique SSN cases were identified.^3–30 This paper is in compliance with the ethical principles outlined in the Declaration of Helsinki as amended in 2013. IRB review and approval was not required given the scope of this project. This case report is also in compliance with HIPAA for the collection and evaluation of protected patient health information.

Case report

A previously healthy patient in their 40s was referred for a 2-year history of blurred vision in both eyes, left greater than right. They reported diminished peripheral vision bilaterally, intermittent horizontal diplopia, and headaches without transient visual obscurations, pulsatile tinnitus, or other neurological deficits. The review of the systems was otherwise unremarkable.

On initial examination, visual acuity was 20/40 in the right eye (OD) and 20/80 in the left (OS). Intraocular pressure was normal bilaterally. The pupillary examination did not reveal an afferent pupillary defect. Extraocular movements were full, however, the patient displayed pendular SSN (Supplementary Video 1). They had a small angle (4 prism dioptre) exotropia in primary gaze. Ishihara colour plate testing was full (11/11) OD and diminished (3/11) OS. Ophthalmological examination was also significant for bilateral optic disc pallor.

Optical coherence tomography (OCT) depicted retinal nerve fibre layer thinning in both eyes. Standard automated perimetry (30–2) identified a bitemporal hemianopia involving fixation (Figure 1).

Figure 1.

Standard automated perimetry testing 30 degrees around fixation revealing bilateral temporal hemianopia in the left (a) and right (b) eyes before resection of the pituitary adenoma, and improvement in the visual field deficits 1.5 years following resection (left eye c, right eye d).

Magnetic resonance imaging (MRI) of the brain and orbits revealed a 2.8 × 2.7× 2.8 cm pituitary macroadenoma abutting the undersurface of the column of the fornix, with superior displacement of the optic chiasm (Figure 2). There was no evidence of cavernous sinus invasion.

Figure 2.

(a) axial T1 post-contrast magnetic resonance imaging (MRI) and (b) coronal TI fat-suppressed pre-contrast MRI depicting a pituitary macroadenoma, 2.8 × 2.7 × 2.8 cm in size. There is superior displacement of the optic chiasm. The lesion abuts the undersurface of the column of the fornix.

Endocrine evaluation revealed secondary hypothyroidism, otherwise normal hormone function. The patient underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma, and no evidence of residual tumour was identified post-operatively. Histopathological analysis was consistent with a non-functioning pituitary adenoma. Their nystagmus resolved immediately after surgery during hospitalisation. A video was obtained when they were evaluated 13 days following surgery (Supplementary Video 2). The patient was evaluated 1.5 years following the surgical resection and was found to have improvement in the bitemporal hemianopia (Figure 1), and an MRI revealed complete resolution of the lesion with post-surgical changes (Figure 3). Additionally, the nystagmus remained fully resolved.

Figure 3.

(a) axial T2 magnetic resonance imaging (MRI) and (b) coronal T1 MRI depicting post-surgical changes and resolution of the pituitary macroadenoma 1.5 years following resection of the lesion.

Literature review

The results of the PubMed search of peer-reviewed literature conducted between 2002 and 2022 are presented in Table 1.^3–30 The average age of presentation was 42.2 (range 4–68) years old. Common presenting symptoms included oscillopsia (38%), vertigo (28%), symptoms concerning for stroke including gait disturbances, unilateral weakness/paresthaesia, and dysarthria (24%), decreased/blurry vision (21%), headache (17%) and diplopia (14%). The pendular (66%) subtype was more prevalent than jerk (34%) nystagmus. The location of the lesion causing SSN included pathologies of the chiasm (38%), the brainstem (34%), and the cerebellum (10%). Of these, 34% were secondary to neurological infarctions, while 24% were related to mass effect from tumours. Other causes included: trauma (7%); syndromic conditions such as Joubert and VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-oesophageal fistula, renal anomalies, and limb abnormalities) syndrome (17%); inflammatory conditions (7%); radiation (3%); and medication-induced cases (7%). Cases from chiasmal disturbances often presented with bitemporal hemianopia (73% out of those tested; 11/15). The optic discs were noted to be pale or atrophic in 60% of cases, otherwise fundoscopic examinations were normal. Medications suspected of SSN induction included mefloquine and oxcarbazepine.

Table 1.

Published cases of see-saw nystagmus.

Reference	Age (years) and sex	Presenting pattern of the SSN	Anatomical location/cause	Aetiology	Intervention	Resolution
Pal et al.5	5 F	Pendular	Chiasm	Chiasmal compression from a craniopharyngioma	Transfrontal excision	Yes, after 1 month
Saluja et al.4	4 F	Pendular	Chiasm	Chiasmal compression from a craniopharyngioma	N/A	N/A
Nguyen et al.6	40 M	Pendular	Chiasm	Achiasma from VACTERL syndrome	Conservative management of hydrocephalus	No
Eggenberger7	45 M	Pendular	Chiasm	Delayed onset from chiasmal injury after a traumatic brain injury	Gabapentin, baclofen, and clonazepam	Yes, on maintained clonazepam therapy. No improvement with gabapentin and baclofen monotherapy
Eggenberger7	58 M	Pendular	Chiasm	Delayed onset from chiasmal injury after a traumatic brain injury	Deferred by the patient	No
Rudich et al.8	37 F	Pendular	Chiasm	Chiasmal hypoplasia from septo-optic dysplasia	N/A	N/A
Prakash et al.9	29 M	Pendular	Chiasm	Achiasma from VACTERL syndrome	N/A	N/A
Hari Kumar et al.10	52 M	Pendular	Chiasm	Chiasmal compression from a pituitary adenoma	Trans-sphenoidal hypophysectomy	Yes, after 3 months
Woo et al.11	55 F	Pendular	Chiasm	Chiasmal compression from a pituitary macroadenoma	Anterior interhemispheric transcallosal near-total excision	No, after 6 months
Moura et al.12	50 M	Pendular	Chiasm	Chiasmal compression from a pituitary macroadenoma	Trans-sphenoidal tumour removal	Resolved after a few months
Liu et al.13	59 F	Pendular	Chiasm	History of a tuberculum sellae meningioma resected 3 years prior to SSN onset	Clonazepam	Improved promptly with clonazepam therapy
Oh et al.14	47 F	Jerk	Brainstem	Right dorsomedial pontine tegmental lesion	Observation	Improved after 4 days
Khan et al.15	50 M	Jerk, intermittent	Brainstem	Right lateral medullary infarction	N/A	N/A
Choi et al.16	46 F	Jerk	Brainstem	Dorsomedial pontine infarction	Antiplatelet therapy	Yes, within 7 days
Lee et al.17	62 F	Jerk	Brainstem	Left rostral medial medullary infarction	Antiplatelet therapy	Near resolution after 2 months
Choi et al.18	20 M	Jerk	Brainstem	Bilateral medial medullary infarction	Anticoagulation	No, after 6 months
Zhang et al.19	62 M	Pendular	Brainstem	Bilateral dorsomedial pons and left thalamus infarction	Antithrombotic therapy	Improved after 2 weeks
Man et al.20	49 F	Pendular	Brainstem	Right thalamo-mesencephalic infarction	Aspirin and rehabilitation training	Yes, after 2 months
Gong et al.21	33 F	Jerk	Brainstem	Medullary astrocytoma	Surgical tumour resection	No improvement after 1 month
Porta-Etessam et al.22	61 M	Pendular	Brainstem	Dorsolateral medullary infarction	N/A	N/A
Cakir et al.23	45 F	Jerk	Brainstem	Hyperintense lesion in the pons on T2-weighted MRI secondary to SLE	Pulsed IVMP	Improved within 1 week, no recurrence in 1 year
Jang et al.24	18 M	Jerk	Brainstem	Midbrain-hindbrain malformation in the setting of Joubert syndrome	N/A	N/A
Quisling et al.3	64 M	Pendular	Mixed	Distant traumatic chiasmal injury with superimposed right lateral pontine infarction	Clonazepam	Improved but not resolved with initial clonazepam dosage; no follow up
Sandramouli et al.25	33 F	Pendular	Mixed	Suspected radiographically-occult lesion from MS	N/A	N/A
Fridman et al.26	38 M	Pendular	Mixed	Possible radiation-associated insult 8 years due to external beam therapy for a large mesodiencephalic mass	N/A	N/A
Byju et al.27	16 M	Pendular	Cerebellum	Cerebellar vermian agenesis from Joubert syndrome	N/A	N/A
Lee et al.28	68 M	Jerk	Cerebellum	Left cerebellar infarction in the superior cerebellar artery territory involving the superior cerebellar peduncle	N/A	N/A
Manto et al.29	36 F	Pendular, intermittent	Medication	Mefloquine-induced (subjective oscillopsia development 6 hours after the first dose)	Discontinue Mefloquine	Oscillopsia improved after days and SSN after 1 week
Adamec et al.30	43 F	Jerk	Medication	Oxcarbazepine-induced	Switched from oxcarbazepine and lamotrigine to carbamazepine	Improved after 1 week

F = female; IVMP = intravenous methylprednisolone; M = male; MRI = magnetic resonance imaging; MS = multiple sclerosis; SLE = systemic lupus erythematosus; SSN = see-saw nystagmus; VACTERL = vertebral defects, anal atresia, cardiac defects, tracheo-oesophageal fistula, renal anomalies, and limb abnormalities.

Management decisions were based on aetiology including: medical management, such as reduction of stroke risk factors with the initiation of antiplatelet therapy or anticoagulation; excision of the offending mass; conservative management; or cessation of the offending medications. Of the cases with follow-up, resolution and/or significant improvement in the nystagmus was seen in most cases (74%) following treatment. In cases of SSN secondary to neurological infarcts, 86% demonstrated either resolution or significant improvement following treatment. Conversely, for cases attributed to a mass aetiology, the rate of resolution or significant improvement was observed to be 50% after lesion excision. Notably, in instances of medication-induced SSN, a complete resolution or significant improvement was observed in 100% of these cases.

Discussion

See-saw nystagmus often co-occurs with bitemporal hemianopia as clinical manifestations of sellar lesions.² However, SSN can also occur independently of significant field deficits, suggesting that the underlying pathophysiology is not isolated to the afferent visual pathways. There are two proposed mechanisms for SSN resulting from afferent dysfunction. A torsional adaptive process that attempts to increase overlap of non-corresponding nasal visual fields may be implicit.³¹ Additionally, there could also be disruption of the visuo-vestibular connections between the retina and inferior olive.³²

Previous isolated reports have described the resolution of SSN and bitemporal hemianopia due to compressive aetiologies.^5,33,34 Our patient presented with a sellar mass and afferent visual dysfunction that may have been a contributing factor prompting the development of nystagmus. While the exact mechanism of afferent and efferent contributions to the development of SSN in our patient is unclear, they demonstrated immediate resolution of the nystagmus following resection of the pituitary macroadenoma. Additionally, with 1.5 years of follow-up after the resection we note an improvement in the patient’s bitemporal hemianopia and full resolution of the nystagmus.

Currently, the degree of improvement in both bitemporal hemianopia and nystagmus following treatment of the aetiologies causing SSN remains scarcely reported in the literature. There is remarkable reported improvement in the cases of SSN due to medication (100%) and neurological infarctions (86%), while excision of the causative mass lesion resulted in 50% of cases experiencing improvement. Similarly underreported is information regarding prognosis related to factors such as tumour size, location, and duration of compression. Importantly, other causes of SSN include head trauma, multiple sclerosis, Chiari Type II malformation and intrathecal methotrexate, and these may have differing outcomes.³

In our literature review, we have identified two specific medications: mefloquine and oxcarbazepine as causative agents for SSN. With regards to oxcarbazepine, it is hypothesised that blockade of ion within neurons in the medial longitudinal fasciculus leads to the observed nystagmus. Intriguingly, upon discontinuation of oxcarbazepine, this effect is reversed, resulting in the resolution of the nystagmus.³⁰ Manto et al. reported a case of mefloquine-induced SSN in a patient with spinocerebellar ataxia type 2. The authors postulate that calcium may play a pivotal role in the pathogenesis of nystagmus in ataxia patients, and a disturbance in the homoeostasis of the posterior fossa structures may be implicit in this patient specifically, due to the drug’s mechanism of action, which inhibits the calcium release from inositol-1,4,5-phosphate-sensitive stores in the brain.²⁹ Pharmacologically, clonazepam has been proposed as a therapeutic intervention for SSN. Although the exact mechanism remains incompletely elucidated, it is believed to act by augmenting inhibitory GABAergic synaptic transmission.³⁵ This modulation is likely to contribute to the observed improvement of nystagmus seen.

We have reported a case with immediate resolution of SSN after resection of a pituitary macroadenoma causing chiasmal compression. Similar complete resolution of SSN has been described in three previous case reports after tumour resection: one subtotal resection of a craniopharyngioma⁵ and two total resections of pituitary macroadenomas, but they were noted to have resolution from 1–3 months post-resection.^5,10,12 Conversely, Yat-Ming Woo et al. reported a case of SSN which did not resolve following resection of a pituitary macroadenoma.¹¹ Additionally, there was a lack of improvement in the bitemporal hemianopia, which is suggestive of the theory of SSN being secondary to an adaptive process aimed at increasing the overlap between non-corresponding nasal visual fields.

Overall, in our literature review, SSN resolved in 74% of cases after sellar tumour resection. Further research will be important to elucidate if factors such as tumour size, location, and duration of compression may be contributing factors to patient outcomes.

Consent

Written informed consent for publication of their details was obtained from the patient.

Funding Statement

The authors reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Affirmations

Affirmation of compliance with the ethical principles outlined in the Declaration of Helsinki as amended in 2013, affirmation of compliance with HIPAA for the collection and evaluation of protected patient health information.

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01658107.2023.2299763.