A rare diagnosis of nine syndrome: Clinical, imaging findings, and literature review Ng CY, Yong GY, Ngai JJ, Zainal-Abidin ZB,

CASE REPORT

Ahead of print publication

A rare diagnosis of nine syndrome: Clinical, imaging findings, and literature review

Chin-Yee Ng¹, Geng-Yi Yong², Jia-Jeane Ngai³, Zairah Binti Zainal-Abidin³
¹ Department of Ophthalmology, Hospital Tengku Ampuan Rahimah, Selangor, Malaysia
² Department of Ophthalmology, University of Malaya, Kuala Lumpur, Malaysia
³ Department of Ophthalmology, Ampang Hospital, Selangor, Malaysia

Date of Submission	23-Jul-2022
Date of Acceptance	14-Oct-2022
Date of Web Publication	01-Feb-2023

Correspondence Address:
Chin-Yee Ng,
Department of Ophthalmology, Hospital Tengku Ampuan Rahimah, Jalan Langat, 41200, Klang, Selangor
Malaysia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjo.TJO-D-22-00092

Abstract

In this article, we reported a rare case of nine syndrome, which is characterized by clinical signs of the one-and-a-half syndrome, ipsilateral facial palsy, contralateral hemiparesis, hemihypesthesia, or ataxia. A 44-year-old male presented with sudden onset of double vision for 3 days. Examination revealed left horizontal gaze palsy, internuclear ophthalmoplegia, left lower motor neuron facial nerve palsy with right hemiplegia, and hemihypesthesia. Magnetic resonance imaging brain showed evidence of acute infarction at the left paramedian pons. Magnetic resonance angiography revealed a beaded small-caliber basilar artery suggestive of intracranial vasculopathy in the posterior circulation. The patient has been treated with an antiplatelet and lipid-lowering agent. His right hemiparesis has improved, but the ocular motility and left facial paresis persisted. The literature reviews of 14 cases of nine syndrome were discussed, and the biography background, clinical pictures, etiology, neuroimaging, treatment, and recovery status were described.

Keywords: Eight-and-a-half syndrome, horizontal gaze palsy, paramedian pontine, pseudoptosis

How to cite this URL:
Ng CY, Yong GY, Ngai JJ, Zainal-Abidin ZB. A rare diagnosis of nine syndrome: Clinical, imaging findings, and literature review. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Apr 2]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=369010

Introduction

Nine syndrome is a rare neuro-ocular presentation, characterized by clinical signs of the one-and-a-half syndrome, ipsilateral facial palsy, contralateral hemiparesis, hemihypesthesia, or ataxia.^[1] Nine syndrome occurred due to lesions located in the unilateral tegmentum of the caudal pontine plus paramedian pontine.^[2] We present a case of nine syndrome, discussing the clinical presentation, the role of different modalities of neuroimaging for diagnosis, and a review of the literature.

Case Report

A 44-year-old smoker with no background history of medical illness presented with sudden onset of double vision, right body weakness, left facial weakness, dizziness, and vomiting for 3 days. There was no blurry vision, hearing loss, slurred speech, urine, or bowel incontinence. On examination, he had right exotropia, right pseudoptosis [Figure 1], and left lagophthalmos. Ocular motility examination showed a complete absence of left adduction and abduction, impaired right adduction [Figure 2], and the presence of horizontal nystagmus on right abduction. The convergence was normal. In addition, the patient had left lower motor neuron facial nerve palsy with right hemiplegia and hemihypesthesia. Cerebellar signs were negative. The vision was normal. Both pupils were normal, reacting to light, and had no anisocoria. There was no visual field defect. Magnetic resonance imaging (MRI) brain showed evidence of acute infarction at the left paramedian pons [Figure 3] and signs of chronic infarction at the right cerebellar cortex and white matter at the left cerebellar hemisphere. Magnetic resonance angiography (MRA) showed a small-caliber basilar artery with a beaded appearance suggestive of intracranial vasculopathy in the posterior circulation. Diagnosis of nine syndrome secondary to the cerebrovascular accident was made. Investigations for young stroke discovered the patient has dyslipidemia, and other blood investigations were unremarkable. The patient has been co-managed with the medical team and treated with a long-term antiplatelet and lipid-lowering agent. After 1 week of admission, an improvement was seen in his right hemiparesis. However, the ocular motility and left facial paresis persisted. The patient was discharged with an appointment with the cardiology department for further investigation of a young stroke. In subsequent follow-ups, the echocardiogram and cardiac stress test reveal a diagnosis of coronary artery disease. The coronary angioplasty and stent were planned.

Figure 1: Left lower motor neuron facial nerve palsy: Loss of left forehead wrinkling left brow ptosis, left upper and lower lid weakening with the widening of the palpebral fissure, and loss of left nasolabial fold

Click here to view

Figure 2: Nine cardinal positions of gaze. There was right exotropia on the primary gaze. Horizontal ocular motility showed left eye horizontal gaze palsy with right eye adduction palsy

Click here to view

Figure 3: The MRI brain showed the ill-defined area at the left paramedian pons, which demonstrated iso to hypointense signal on T1- weighted (right), hyperintense in T2-weighted (middle), and restricted diffusion on diffusion-weighted imaging (left). MRI = Magnetic resonance imaging

Click here to view

In a 1-year follow-up after the cerebrovascular event, the double vision was resolved. The left facial weakness and right body weakness were improved; while the hemihypesthesia resolved. Ocular examination showed resolved horizontal nystagmus and improvement of ocular motility in left abduction, left abduction, and right adduction [Figure 4].

Figure 4: Nine cardinal positions of gaze at 1-year follow-up. There was minimal right exotropia on the primary gaze. Horizontal ocular motility improved with normal left eye abduction, slight restriction of left eye adduction (-1), and minimum restriction of right eye adduction

Click here to view

Discussion

The one-and-a-half syndrome is a neuro-ophthalmic condition proposed by Fisher in 1967.^[3] It is clinically characterized by the combination of ipsilateral conjugate horizontal gaze palsy and ipsilateral internuclear ophthalmoplegia due to a lesion involving the ipsilateral abducens nucleus or paramedian pontine reticular formation, and the ipsilateral medial longitudinal fasciculus.^[3] In 1998, Eggenberger observed that the lesion could extend to involve the adjacent ipsilateral facial colliculus owing to their proximity, causing ipsilateral lower motor neuron cranial nerve VII palsy, which he termed "Eight-and-a-half syndrome" (EAHS).^[4] EAHS with contralateral transient hemiparesis was proposed by Uysal et al. in 2012.^[5] Subsequently, Rosini et al., in 2013, reported her case of EAHS associated with contralateral hemiparesis and hemihypesthesia and referred to this constellation as the possible nine syndrome.^[6] The additional clinical features were consistent with the MRI brain findings, whereby the corticospinal tract and medial lemniscus were concomitantly involved.^[6] Through our literature search, we found 14 other cases of nine syndrome being reported [Table 1]. There were 9 (64.3%) cases of males, and 5 (35.7%) cases were females. Most cases (71.4%) were from Asia. There were 5 (35.7%) cases reported having both contralateral hemiparesis and hemihypesthesia; 3 (21.4%) cases with only contralateral hemiparesis; 4 (28.6%) cases with only hemiataxia; and 1 (7.1%) case with only hemihypesthesia. On the one hand, Mahale et al. reported a case of ipsilateral hemiataxia, which was caused by an additional lesion involving the ipsilateral inferior cerebellar peduncle in the rostral dorsolateral medulla.^[7] On the other hand, the three reported cases with contralateral hemiataxia involved the extension of a lesion at the caudal pontine tegmentum into the midbrain tegmentum or red nucleus.^[7],[8],[9] While, Tiwari et al. reported a case of ipsilateral hemiplegia, which is possible due to an infarct lesion involving the pontomedullary region.^[10] The finding described by Singhdev J et al. as a "partial ptosis" at the contralateral to the facial nerve palsy side was also found in our case [Figure 1]. The loss of innervation to orbicularis oculi at the side of facial nerve palsy allows unopposed action of levator superioris innervated by the oculomotor nerve.^[11] The asymmetrical lid heights with higher eyelids, commonly at the facial nerve palsy side, result in a pseudoptosis on the contralateral eye.^[11] Cerebrovascular accident was the most common cause of nine syndrome. There were 8(57.1%) cases^{[1],[2],[5],[6],[8],[10],[12],[13]} caused by ischaemic stroke, of which one was secondary to systemic lupus erythematosus (SLE) vasculitis^[13], followed by 3(21.4%) cases^{[7],[14],[15]} secondary to hemorrhagic stroke. Other uncommon causes were demyelinating disease (7.1%)^[7]and acute disseminated encephalomyelitis (7.1%)^[9]. Although most of the cases reported were elderly, nine syndrome may affect the younger age group with underlying medical conditions such as SLE and acute disseminated encephalomyelitis. After the etiology of nine syndrome was identified, patients have managed accordingly. Contrasted computed tomography (CT) brain, MRI, and MRA were the neuroimaging modalities used in achieving the diagnosis of the nine syndrome cases. Contrasted CT brain was done in two hemorrhagic stroke cases to localize the lesion. Nevertheless, contrasted CT brain compared to MRI is suboptimal to detect lesions in the midbrain and pontine area due to beam hardening artifacts at the base of the skull. In addition, MRA has proven to be useful in the evaluation of intracranial vasculopathy.^[4] Detection of basilar artery stenosis and cerebral artery occlusion from MRA, in combination with their MRI findings, guided the therapeutic decision-making process of the three cases. Most case reports (35.7%) did not mention the recovery status of the patients. One case achieved complete resolution of symptoms in 3 months and EAHS. The remaining cases reported partial or no recovery of EAHS. The recovery in terms of timing and neurological symptoms was variable. The signs and symptoms may persist in many patients regardless of the underlying causes.

Table 1: Cases of Nine Syndrome and the Clinical Presentations and Management

Click here to view

Conclusion

Through this case and other cases of nine syndrome reported in the literature, the salient clinical features which are helpful in the localization of the lesion could be determined. As more cases of the one-and-a-half syndrome and its spectrum disorders are being recognized and reported, this new clinical entity can be of significant diagnostic value in conjunction with the MRI.

Declaration of patient consent

The authors certify that they have obtained written consent from the patient in the appropriate patient consent form. The patient has given his consent for his image and other clinical information to be reported in the journal. The patient understands that his image may be seen by members of the general public or medical researchers, but his name and initials will not be published.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors declare that there are no conflicts of interests of this paper.

References

1.	Singhdev J, Asranna A, Sureshbabu S, Mittal GK, Singla S, Peter S, et al. Nine syndrome: Case report and review of clinical signs in internuclear ophthalmoplegia. Ann Indian Acad Neurol 2018;21:325-7. [PUBMED] [Full text]
2.	Cao S, Wang R, Xia M, Xu W. Atypical "nine" syndrome in bilateral pontine infarction. Medicine 2019;98:e16378.
3.	Fisher CM. Some neuro-ophthalmological observations. J Neurol Neurosurg Psychiatry 1967;30:383-92.
4.	Eggenberger E. Eight-and-a-half syndrome: One-and-a-half syndrome plus cranial nerve VII palsy. J Neuroophthalmol 1998;18:114-6.
5.	Uysal S, Demirtas-Tatlidede A, Selcuk OY, Yayla V. Diffusion-weighted imaging in eight-and-a-half syndrome presenting with transient hemiparesis. Clin Neuroradiol 2013;23:235-6.
6.	Rosini F, Pretegiani E, Guideri F, Cerase A, Rufa A. Eight and a half syndrome with hemiparesis and hemihypesthesia: The nine syndrome? J Stroke Cerebrovasc Dis 2013;22:e637-8.
7.	Mahale RR, Mehta A, John AA, Javali M, Abbas MM, Rangasetty S. "Nine" syndrome: A new neuro-ophthalmologic syndrome: Report of two cases. Ann Indian Acad Neurol 2015;18:335-7. [PUBMED] [Full text]
8.	Ng YM, Kang PS, Khor CG, Seung OP, Ramanathan GRL. "Nine" syndrome and its MRI brain findings. Neurol Asia 2017;22:349-52.
9.	Uthman M, Kamran M. Case report of a patient with 'one-and-a-half plus syndrome: Nine syndrome'. Oxford Med Case Rep 2018;1:27-9.
10.	Tiwari N, Sharma S, Madhusudan BK, Mathad V. "Nine syndrome": A rare neuroophthalmological syndrome associated with HIV vasculopathy. Indian J Neurosurg 2020;9:49-51.
11.	Sinha KR, Rootman DB, Azizzadeh B, Goldberg RA. Association of eyelid position and facial nerve palsy with unresolved weakness. JAMA Facial Plast Surg 2016;18:379-84.
12.	Maas RP, Verrips A. Teaching Video NeuroImages: Nine syndrome in inferior paramedian pontine infarction: More than meets the eye. Neurology 2017;89:e95-6.
13.	Salazar H, Sadaka A, Berry S, Torres P, Lee AG. Nine syndrome in a patient with systemic lupus erythematosus. Can J Ophthalmol 2018;53:e52-5.
14.	Yadegari S, Aghsaei-Fard M, Akbari M, Mirmohammad-Sadeghi A. "Eight and a half" and "nine syndrome" rare presentation of pontine lesions; case reports and review of literature. Iran J Neurol 2018;17:189-91.
15.	Giuffrè GM, Iorio R, Masi G, Frisullo G, Luigetti M. Nine syndrome. Acta Neurol Belg 2019;119:475-6.