Isolated ocular motor nerve palsy associated with raised homocysteine: A prospective case series

Suchismita Mishra; Jasmita Satapathy; Chinthala Navyasree

doi:10.4103/ijo.IJO_1327_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 1 | Page : 126-129

Isolated ocular motor nerve palsy associated with raised homocysteine: A prospective case series

Suchismita Mishra, Jasmita Satapathy, Chinthala Navyasree
Department of Ophthalmology, IMS and SUM Hospital, Bhubaneswar, Odisha, India

Date of Submission	27-May-2022
Date of Acceptance	29-Sep-2022
Date of Web Publication	20-Jan-2023

Correspondence Address:
Jasmita Satapathy
Department of Ophthalmology, IMS and SUM Hospital, Bhubaneswar - 751 003, Odisha
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1327_22

Abstract

Ocular motor mono-neuropathies frequently occur from micro-vascular ischemia to the nerve in the presence of atherosclerotic risk factors such as old age, diabetes mellitus, hypertension, and dyslipidemia. Other possible causes include trauma, intra-cranial neoplasm, aneurysm, inflammation, infection, and brainstem infarction. Recently, hyper-homocysteinemia has emerged as an independent risk factor for systemic and ocular vaso-occlusive disorders. Ocular pathologies such as retinal vascular occlusion and non-arteritic anterior ischemic optic neuropathy have been found to be associated with mild hyper-homocysteinemia. This case series describes four patients with isolated third and sixth cranial nerve palsy where hyper-homosysteinemia was the only risk factor.

Keywords: Hyper-homocysteinemia, isolated cranial nerve palsy, mono-neuropathy, serum homocysteine

How to cite this article:
Mishra S, Satapathy J, Navyasree C. Isolated ocular motor nerve palsy associated with raised homocysteine: A prospective case series. Indian J Ophthalmol Case Rep 2023;3:126-9

How to cite this URL:
Mishra S, Satapathy J, Navyasree C. Isolated ocular motor nerve palsy associated with raised homocysteine: A prospective case series. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Apr 2];3:126-9. Available from: https://www.ijoreports.in/text.asp?2023/3/1/126/368133

Micro-vascular ischemia is presumed to be one of the leading causes of ocular motor nerve palsy, especially in the elderly age group.^[1] In the past few years, hyper-homocysteinemia (HHcy) has generated considerable interest as a risk factor for the development of atherosclerosis by exerting toxic effects on endothelial cells, the vascular wall structure, and the blood coagulation system.^[2] Association of HHcy with eye diseases such as proliferative diabetic retinopathy, exudative age-related macular degeration, pseudo-exfoliative glaucoma, cataract, optic atrophy, and retinal vessel atherosclerosis is established.^[3] Vitamins B6, B12, and folate (B-vitamins) are important regulators of Hcy metabolism.^[4] Low intake of these nutrients is associated with increased blood Hcy concentrations and can lead to various ocular sequlae. Here, we report four cases of non-traumatic isolated ocular motor nerve palsy with raised Hcy levels. There was no other risk factor, and the neuro-imaging was inconclusive in all cases.

Case Reports

This is a prospective case series, and the data were collected over a period of 3 years from September 2018 to August 2021. All patients were evaluated, and their demographics, clinical presentations, laboratory results, and clinical outcomes were analyzed.

Our case series comprises four patients who were found to have hyper-homocysteinemia as the only risk factor. Three patients were female, and one was male. Details of cases are shown in '[Table 1]'. The mean age of patients was 52.75 years (range: 44–57 years). One patient presented with drooping of the left eye upper lid. Other three patients had complaints of diplopia. The mean duration of symptoms was 14.75 days (range: 10–20 days).

Table 1: Clinical features and laboratory findings of patients with isolated ocular motor nerve palsy

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All patients had the limitation of ocular movements. The amount of limitation was from -4 to -1, where -4 limitation implied no movement of the eyeball beyond the mid-line and -1 limitation referred to limitation only in the extreme gaze. The mean of horizontal deviation in the primary gaze was 18 prism diopters (range: 12–22 PD). The greatest deviation was noted in the direction of limited movement [Figure 1]a. Anterior segment and fundus examination was unremarkable in all cases.

Figure 1: Nine gaze ocular motility showing (a) limitation of abduction in the left eye in patient 4 at initial visit and (b) complete recovery of abduction at 2 months follow-up

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All patients were found to have elevated serum homocysteine. The mean serum homocysteine level was 17.57 μmol/L (range: 14.7–22.6 μmol/L, normal: 4.44–13.56 μmol/L, chemiluminescence microparticle immuno-assay method). Other investigations such as blood pressure, blood sugar, lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein, electrocardiograph (ECG), and carotid doppler were within normal limits. Magnetic resonance imaging (MRI) with contrast showed chronic small vessel ischemic changes in two cases [Figure 2]. In other two patients, MRI was normal. All patients were treated with oral vitamin supplementation (vitamin B6 250 mg, B12 1,500 μg, and folic acid 5 mg) and were observed. After 2–3 months, all patients showed complete resolution of symptoms with normal ocular movements [Figure 1]b. The mean duration of recovery was 7.75 weeks (range: 4–13 weeks).

Figure 2: MRI of the brain showing bilateral small fronto-parital subcortical white matter hyper-intense lesions suggestive of chronic small vessel ischemia in patient 3

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Discussion

Hcy, a non-proteinogenic amino acid, is an intermediate product in the normal bio-synthesis of methionine. B-vitamins are essential co-factors in Hcy-methionine metabolism. Therefore, deficiency of these vitamins can cause impaired re-methylation of Hcy to methionine and lead to Hcy accumulation.^[5],[6] It is a potent atherosclerotic risk factor that promotes thrombus formation and increases the risk of vascular occlusion. A number of ocular vaso-occlusive disorders, including non-arteritic ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), and central retinal vein occlusion (CRVO), have been reported to be associated with HHcy, all of which may result in severe visual loss and ocular morbidity.^[1] In a study by Kawasaki et al.,^[7] around 17% of young patients with NAION were found to have a raised Hcy level as an independent risk factor.^[7] In another study by Pianka et al.,^[8] the authors found 45% patients with NAION and 61.5% patients with CRAO had Hhcy. It has been reported previously that a 5 μmol/L elevation of homocysteine increases the risk of vaso-occlusive diseases by 60% in males and 80% in females.^[1] In a study by Kalita et al.,^[2] around 60% of the patients with ischemic strokes were found to have HHcy.

HHcy can coexist along with other risk factors in cranial nerve palsies.^[9] It was found to be the sole risk factor for isolated abducens nerve palsy in a retrospective case series conducted by Sachdeva et al.^[1] The patients in their study were young with a mean age of 25 years. However, in our series, the mean age was higher (52.75 years), and we found involvement of the isolated oculomotor nerve as well. Similar to previous reports, the majority were females in our study.^[1],[9]

A previous study has reported that elevated homocysteine is a risk factor for cerebral small vessel disease.^[10] We noted small vessel ischemic changes on MRI in two patients, suggesting micro-vasculopathy-induced damage of the cranial nerves for which hyper-homocysteinemia could be a possible risk factor. The other two patients had normal MRI. Similar to our observations, Sachdeva et al.^[1] noted ischemic changes on MRI in 50% of cases with isolated abducens palsy with raised Hcy levels.

Taking supplements of B-vitamins or consuming foods rich in B-vitamins significantly reduces circulating Hcy concentrations.^[1],[2] A recent meta-analysis of 12 randomized controlled trials suggested that dietary supplementation with B-vitamins reduces the risk of stroke by 10%, mainly among individuals who are at high risk of developing vascular disease.^[4] We recommended a course of oral B-vitamin supplementation for all patients and noted complete resolution of symptoms during subsequent follow-up visits.

Conclusion

This case series demonstrates the importance of considering elevated serum Hcy levels as a possible risk factor for non-traumatic isolated cranial nerve palsy in the absence of other co-morbidities. Treatment of HHcy is safe and affordable. Oral vitamin supplementation with folic acid, combined with vitamin B12 and B6, has been shown to decrease homocysteine levels and may be recommended for people with this disorder. Moreover, it is important to understand that many ocular pathologies may present as the initial manifestation of HHcy and should be kept in the differential diagnosis.

Acknowledgements

We thank the Dept of Neurology, IMS and SUM hospital for their support.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Sachdeva V, Mittal V, Pathengay A, Kekkunaya R, Gupta A, Rao BV. Isolated abducens palsy with hyperhomocysteinemia: Association and outcomes. Indian J Ophthalmol 2013;61:598-600. [PUBMED] [Full text]
2.	Kalita J, Kumar G, Bansal V, Misra UK. Relationship of homocysteine with other risk factors and outcome of ischemic stroke. Clin Neurol Neurosurg 2009;111:364-7.
3.	Ajith TA, Ranimenon. Homocysteine in ocular diseases. Clin Chim Acta 2015;450:316-21.
4.	Jenkins DJA, Spence JD, Giovannucci EL, Kim YI, Josse R, Vieth R, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71:2570-84.
5.	Stabler SP. Vitamins, homocysteine, and cognition. Am J Clin Nutr 2003;78:359-60.
6.	Mangge H, Becker K, Fuchs D, Gostner JM. Antioxidants, inflammation and cardiovascular disease. World J Cardiol 2014;6:462-77.
7.	Kawasaki A, Purvin VA, Burgett RA. Hyperhomocysteinemia in young patients with non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 1999;83:1287-90.
8.	Pianka P, Almog Y, Man O, Goldstein M, Sela BA, Loewenstein A. Hyperhomocysteinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology 2000;107:1588-92.
9.	Sharma P, Vashist U. Hyperhomocysteinemia in acquired non-traumatic paralytic strabismus: A case series. J Clin Diagnostic Res 2020;14:BR01-BR03.doi: 10.7860/JCDR/2020/44060.13662.
10.	Hassan A, Hunt BJ, O'Sullivan M, Bell R, D'Souza R, Jeffery S, et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain 2004;127:212-9.