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Isolated abducens nerve palsy with hyperhomocysteinemia

Association and outcomes

Sachdeva, Virender; Mittal, Vaibhev; Pathengay, Avinash1; Kekunnaya, Ramesh2; Gupta, Amit2; Rao, Bhoompally V3

Author Information
Indian Journal of Ophthalmology: October 2013 - Volume 61 - Issue 10 - p 598-600
doi: 10.4103/0301-4738.121089
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Isolated abducens nerve palsy is the most common form of cranial nerve palsies encountered in neuro-ophthalmology clinics and may be idiopathic or due to head trauma, intracranial space occupying lesions, vascular diseases, inflammatory conditions (postviral fever, postinfectious, post-vaccinial) or demyelinating disorders in young patients (<50 years).[1] Hyperhomocysteinemia has been reported as an independent risk factor for systemic and ocular vaso-occlusive disorders, especially in young patients.[234] In this case series, we describe four patients with isolated abducens nerve palsy where hyperhomocysteinemia was the sole risk factor.

Review of Cases

Between November 2008 and October 2010, 27 patients with isolated abducens nerve palsy presented to our clinics. All of these patients underwent evaluation for potential predisposing factors like viral fever, trauma, diabetes, hypertension, collagen vascular disorders, and dyslipidemia. Serum homocysteine levels were determined in those patients without any obvious history of ocular trauma, with or without presence of other risk factors like diabetes, hypertension, and dyslipidemia. Our series comprises of four patients who were found to have hyperhomocysteinemia as the sole risk factor.

Three patients were female and one was male. Details of the cases are shown in Table 1. The mean age of patients was 25 years (range: 6-52 years). All patients presented with complaints of double vision and mean duration of symptoms was 29 days (range: 3-90 days).

Table 1:
Clinical and laboratory features of patients with isolated lateral rectus palsy

All patients had a -4 to -3 limitation of abduction where -4 limitation implied no movement of the eyeball beyond the midline and -1 limitation of abduction referred to limitation of abduction only in extreme abduction. The mean amount of esotropia [Table 1] in primary gaze was 20 prism diopters (range: 12-30 PD, standard deviation (SD) =7.48 PD). Greatest deviation was noted in direction of limitation of movement [Fig. 1a]. Anterior segment and fundus examination was unremarkable. All patients underwent magnetic resonance imaging (MRI) brain with contrast [Fig. 2] which showed only the presence of ischemic lesions in two patients [Table 1]. The erythrocyte sedimentation rate (ESR), C-reactive protein, lipid profile, blood glucose levels, blood pressure, echocardiogram, and carotid Doppler were normal for all patients.

Figure 1:
(a) Nine gaze ocular motility showing incomitant esotropia and limitation of abduction in the right eye in patient 1 at initial visit and (b) at 3 months follow-up showing orthotropia and complete recovery of abduction
Figure 2:
Magnetic resonance imaging brain showing the presence of bilateral white matter hyperintense lesions suggestive of ischemia in patient 2

However, all patients were found to have elevated serum homocysteine. Mean serum homocysteine level was 19.20 μmol/L (range: 16.07-20.50, SD: 2.09 μmol/L, normal: 3.9-13.9 μmol/L, chemiluminescence method). The patients were treated with vitamins B6 (250 mg), B12 (1,500 μg), and folic acid (5 mg). Two patients were given injection botulinum toxin (BOTOX, Allergan, 2.5 IU) in the medial rectus muscle of the affected eye to relieve diplopia while the other two were observed. After 2 months, all patients showed complete resolution with orthotropia in primary gaze and complete recovery of extraocular motility [Fig. 1b].


Hyperhomocysteinemia is characterized by an elevation of serum homocysteine, an intermediate metabolite in methionine metabolism. Homocysteine is a potent atherosclerotic risk factor that leads to formation of the free radicals and promotes smooth muscle proliferation. This promotes thrombus formation and increases the risk of vascular occlusion. Hyperhomocysteinemia is reported as an independent risk factor for systemic and ocular vaso-occlusive disorders, including nonarteritic ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), and central retinal vein occlusion (CRVO), especially in young patients.[234]

It has been reported that as many as 17% of young patients with NAION may have isolated hyperhomocysteinemia as the risk factor.[3]

We have previously reported a case of combined cilioretinal artery obstruction and NAION in a young patient with hyperhomocysteinemia.[4] In another study by Kalita et al.,[5] 60.6% of the patients with ischemic strokes had hyperhomocysteinemia. A 5 μmol/L elevation of homocysteine has been reported to increase risk of vaso-occlusive diseases by 60% in males and 80% in females with an increased odds ratio of 1.4−1.7.[6]

Similar to the previous reports, patients in our series were young with a mean age of 25 years (range: 6-52 years). In our series, all patients presented with isolated abducens nerve palsy without any other known risk factor apart from hyperhomocysteinemia. The presence of the ischemic lesions on MRI in two patients prompted us to think of hyperhomocysteinemia as a possible risk factor. Since we found elevated homocysteine levels in these patients, we investigated for hyperhomocysteinemia in the other patients as well, despite a normal neuroimaging. Abducens nerve involvement in these cases could be attributed to microvasculopathy induced damage similar to that found in diabetic patients with abducens palsy.

Hyperhomocysteinemia is a potentially modifiable risk factor. Dietary supplementation of 250 mg of vitamin B6, 5 mg of folic acid and vitamin B12 daily has been shown to lower serum homocysteine levels.[5] Complete resolution, either spontaneous or following single botulinum injection and oral vitamin supplementation, was noted in all patients as is seen in patients with microvasculopathy as seen in diabetes mellitus.

Although hyperhomocysteinemia has been reported with various vaso-occlusive diseases; however, causal association is still not proven. Population based randomized trials such as CARDIOVIT study,[7] are underway to investigate the association of hyperhomocysteinemia with systemic vaso-occlusive diseases. Until conclusive data is available it is recommended to investigate and treat for hyperhomocysteinemia in cases of vaso-occlusive diseases.

The main limitation of our series is its retrospective nature with limited size. However, this is an uncommon condition and to the best of our knowledge, this is the first reported association of hyperhomocysteinemia with isolated cranial nerve palsy. Based on our findings we recommend estimation of serum homocysteine in the work up of young patients with nontraumatic isolated abducens nerve palsy in the absence of other risk factors.


We acknowledge the support of Dr. Merle Fernandes, Director and Consultant, Cornea and Anterior segment services in the English language editing for the manuscript.

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2. 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
3. Kawasaki A, Purvin VA, Burgett RA. Hyperhomocysteinemia in young patients with non-arteritic anterior ischaemic optic neuropathy Br J Ophthalmol. 1999;83:1287–90
4. Ravi C, Ramesha K, Sachdeva V, Pathengay A, Rao BV. A case of presumed association of Hyperhomocysteinemia-with NAION and Cilioretinal artery obstruction Asian J Ophthalmol. 2009;11:32–4
5. 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
6. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes JAMA. 1995;274:1049–57
7. Shenoy KT, Lena KS, Sali N, Syam S, Shenoy ST, Rajadhyaksha VD, et al Cardiovit Study Team. Rationale and design for the CARDIOVIT study (Cardiovit Atherosclerotic vascular Disease and hypeRhomocysteinemia: An epidemiological study in Indians, additionally evaluating the effect of Oral VITamin supplementation) Curr Med Res Opin. 2006;22:641–8

Source of Support: Hyderabad Eye Research Foundation, HERF, Hyderabad, Andhra Pradesh, India,

Conflict of Interest: None declared.


Abducens nerve palsy; hyperhomocysteinemia; isolated abducens nerve palsy; nontraumatic

© 2013 Indian Journal of Ophthalmology | Published by Wolters Kluwer – Medknow