BMJ 2014;348:g3286 doi: 10.1136/bmj.g3286 (Published 19 May 2014)
Page 1 of 3
Endgames
ENDGAMES PICTURE QUIZ
Sudden onset double vision Nicholas R Plummer academic foundation year 1 doctor, Thomas Thorp specialty registrar, elderly medicine, Sulaiman Sultan consultant cerebrovascular physician Acute Stroke Unit, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston PR2 9HT, UK
An 83 year old woman was admitted to the acute stroke unit with sudden onset double vision that had lasted for three hours. She had a medical history of monoclonal gammopathy of uncertain significance and atrial fibrillation, for which she was not receiving anticoagulation because of an adverse reaction to warfarin. She had no history of transient ischaemic attack or stroke. She had diplopia only when looking through her right. On examination she was unable to adduct her left eye, with nystagmus in her right eye when she attempted to do this. Her neurological examination was otherwise normal. Computed tomography of the head on admission was normal, as was magnetic resonance imaging of the head, which was requested the next day. Figure 1 shows T2 weighted (A) and diffusion weighted (B) sequences at the level of the upper pons.
Questions 1. What is this eye lesion called, and what is its pathological basis? 2. What does the magnetic resonance image show? 3. What are the differential diagnoses? 4. How should this condition be managed further?
Answers
1. What is this eye lesion called, and what is its pathological basis? Short answer Left internuclear ophthalmoplegia. It is caused by impairment of conjugate eye movements owing to injury to the medial longitudinal fasciculus on the side of the impaired eye.
Long answer
Internuclear opthalmoplegia (INO) is caused by a lesion in the medial longitudinal fasciculus, a heavily myelinated tract that connects the ipsilateral sixth nerve nucleus with the contralateral medial rectus subnucleus. This facilitates conjugate eye movements on lateral gaze.1.
Diplopia in internuclear opthalmoplegia is caused by the failure of conjugate eye movements. Abduction is normal in both eyes, whereas adduction is impaired or absent in the affected eye, resulting in dissociation of eye movements, while the abducting eye shows nystagmus, with the quick phase towards the unaffected side. All other eye movements are usually unaffected, except for the horizontal saccade, where the affected eye lags behind the normal eye, and adduction on convergence may be preserved. The medial longitudinal fasciculus also conveys vertical and tortional eye movement signals, and patients with medial longitudinal fasciculus lesions may have skew deviation—a vertical strabismus where the eyes move in opposite directions equally.
2. What does the magnetic resonance image show? Short answer
The diffusion weighted image shows a small hyperintense lesion in the left upper pons, in the region of the medial longitudinal fasciculus.
Correspondence to: N R Plummer [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
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BMJ 2014;348:g3286 doi: 10.1136/bmj.g3286 (Published 19 May 2014)
Page 2 of 3
ENDGAMES
Long answer
The diffusion weighted image shows a small area of restricted diffusion in the left upper pontine tegmentum, in the region of the left medial longitudinal fasciculus (fig 2).2 This is highly suggestive of an acute posterior circulation infarct.3 Diffusion weighted imaging provides a visual representation of the freedom for water to diffuse through tissue, with hyperintensities (bright white lesions) reflecting areas of restricted diffusion. In acute stroke, this is caused by ischaemia related disruption of energy metabolism, which leads to abolition of transcellular ionic gradients and translocation of water into the intracellular compartment.4
Fig 2 Diffusion weighted image showing a small area of restricted diffusion in the left upper pontine tegmentum (box labelled 1), in the region of the left medial longitudinal fasciculus
Diffusion weighted imaging is particularly sensitive (88-100%) and specific (86-100%) for the detection of hyperacute and acute ischaemic stroke,4 when early computed tomography is often negative. Diffusion weighted imaging is therefore routinely used for differentiating acute stroke from other processes that manifest with sudden neurological deficits, especially in posterior circulation lesions.5 Restricted diffusion associated with acute ischaemia can be imaged within minutes of the event, and hyperintensities remain for up to four weeks after an infarct.
3. What are the differential diagnoses? Short answer
In older patients with vascular risk factors, internuclear opthalmoplegia is most commonly caused by a vascular brainstem lesion, with an infectious process affecting the brainstem less likely. In younger patients, multiple sclerosis should be suspected; in such cases internuclear opthalmoplegia is often bilateral.
Long answer
The most common causes of internuclear opthalmoplegia are vascular lesions (brainstem infarctions), which made up 37% of causes in one long term follow-up study,6 multiple sclerosis (32%), and infectious diseases (14%). Other causes include head trauma, tumours of the brainstem and fourth ventricle (including pontine gliomas in very young people), inflammatory encephalitis affecting the brainstem, Arnold-Chiari malformation, hydrocephalus, and systemic lupus erythematosus.7 Bilateral disease in young people is almost pathognomic for multiple sclerosis, with unilateral disease in older people or those with vascular risk factors probably being indicative of posterior circulation stroke.
4. How should this condition be managed further? Short answer
Secondary prevention should be initiated, including anticoagulation for atrial fibrillation with a novel oral anticoagulant. The patient should also be referred to occupational therapy and orthoptic services to aid rehabilitation of any persistent visual deficit.
Long answer
Visual complications are common after stroke, with impairment in eye alignment and movement affecting 68% of patients in one study.8 Such complications can interfere with rehabilitation and return to independence in activities of daily living.9 Options for treating diplopia after stroke include visual retraining therapy; occluding one eye, either completely or over the region creating diplopia only; or use of optic prisms. Strabismus surgery can be performed if orthoptic input does not improve diplopia in the longer term. Atrial fibrillation is a major risk factor for ischaemic stroke. The National Institute for Health and Care Excellence (NICE) recommends warfarin as the first line thromboprophylactic agent in those with cardiovascular risk factors,10 11 although dosing and monitoring can be complicated and adverse drug reactions do occur. NICE has approved several novel oral anticoagulants with a similar efficacy and safety profile to those of warfarin in patients who cannot tolerate warfarin (the direct thrombin inhibitor dabigatran, and direct factor Xa inhibitors rivaroxaban and apixaban).12 Draft guidelines suggest an increasing role for these drugs as first line prevention.
Patient outcome The patient recovered most of her visual function. Carotid Doppler ultrasound was normal and echocardiography showed no definitive thrombus, so it was presumed that this was a cardioembolic stroke secondary to atrial fibrillation. After being started on anticoagulation with dabigatran because of a CHA2DS2-VASc score for stroke risk in atrial fibrillation of 6, she was discharged home after occupational therapy input, with follow-up by the orthoptic service in clinic. Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: None. Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent obtained. 1 2 3 4 5 6 7 8 9 10
For personal use only: See rights and reprints http://www.bmj.com/permissions
Keane JR. Internuclear ophthalmoplegia: unusual causes in 114 of 410 patients. Arch Neurol 2005;62:714-7. Atlas SW, Grossman RI, Savino PJ, Schatz NJ, Sergott RC, Bosley TM, et al. Internuclear ophthalmoplegia: MR-anatomic correlation. AJNR Am J Neuroradiol 1987;8:243-7. Kim JS. Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction. Neurology 2004;62:1491-6. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology 2000;217:331-45. Van Everdingen KJ, van der Grond J, Kappelle LJ, Ramos LM, Mali WP. Diffusion-weighted magnetic resonance imaging in acute stroke. Stroke J Cerebr Circ 1998;29:1783-90. Bolaños I, Lozano D, Cantú C. Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand 2004;110:161-5. Obuchowska I, Mariak Z. [Internuclear ophthalmoplegia—causes, symptoms and management.] Klin Oczna 2009;111:165-7. Rowe F, Brand D, Jackson CA, Price A, Walker L, Harrison S, et al. Visual impairment following stroke: do stroke patients require vision assessment? Age Ageing 2009;38:188-93. Jones SA, Shinton RA. Improving outcome in stroke patients with visual problems. Age Ageing 2006;35:560-5. National Institute for Health and Care Excellence. Atrial fibrillation. CG36. 2006. http:// guidance.nice.org.uk/CG36.
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g3286 doi: 10.1136/bmj.g3286 (Published 19 May 2014)
Page 3 of 3
ENDGAMES
11 12
Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994;343:687-91. Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS, et al. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention
of venous thromboembolism: systematic review and network meta-analysis. BMJ 2013;347:f5133.
Cite this as: BMJ 2014;348:g3286 © BMJ Publishing Group Ltd 2014
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
Page 1 of 3
Endgames
ENDGAMES PICTURE QUIZ
Sudden onset double vision Nicholas R Plummer academic foundation year 1 doctor, Thomas Thorp specialty registrar, elderly medicine, Sulaiman Sultan consultant cerebrovascular physician Acute Stroke Unit, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston PR2 9HT, UK
An 83 year old woman was admitted to the acute stroke unit with sudden onset double vision that had lasted for three hours. She had a medical history of monoclonal gammopathy of uncertain significance and atrial fibrillation, for which she was not receiving anticoagulation because of an adverse reaction to warfarin. She had no history of transient ischaemic attack or stroke. She had diplopia only when looking through her right. On examination she was unable to adduct her left eye, with nystagmus in her right eye when she attempted to do this. Her neurological examination was otherwise normal. Computed tomography of the head on admission was normal, as was magnetic resonance imaging of the head, which was requested the next day. Figure 1 shows T2 weighted (A) and diffusion weighted (B) sequences at the level of the upper pons.
Questions 1. What is this eye lesion called, and what is its pathological basis? 2. What does the magnetic resonance image show? 3. What are the differential diagnoses? 4. How should this condition be managed further?
Answers
1. What is this eye lesion called, and what is its pathological basis? Short answer Left internuclear ophthalmoplegia. It is caused by impairment of conjugate eye movements owing to injury to the medial longitudinal fasciculus on the side of the impaired eye.
Long answer
Internuclear opthalmoplegia (INO) is caused by a lesion in the medial longitudinal fasciculus, a heavily myelinated tract that connects the ipsilateral sixth nerve nucleus with the contralateral medial rectus subnucleus. This facilitates conjugate eye movements on lateral gaze.1.
Diplopia in internuclear opthalmoplegia is caused by the failure of conjugate eye movements. Abduction is normal in both eyes, whereas adduction is impaired or absent in the affected eye, resulting in dissociation of eye movements, while the abducting eye shows nystagmus, with the quick phase towards the unaffected side. All other eye movements are usually unaffected, except for the horizontal saccade, where the affected eye lags behind the normal eye, and adduction on convergence may be preserved. The medial longitudinal fasciculus also conveys vertical and tortional eye movement signals, and patients with medial longitudinal fasciculus lesions may have skew deviation—a vertical strabismus where the eyes move in opposite directions equally.
2. What does the magnetic resonance image show? Short answer
The diffusion weighted image shows a small hyperintense lesion in the left upper pons, in the region of the medial longitudinal fasciculus.
Correspondence to: N R Plummer [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g3286 doi: 10.1136/bmj.g3286 (Published 19 May 2014)
Page 2 of 3
ENDGAMES
Long answer
The diffusion weighted image shows a small area of restricted diffusion in the left upper pontine tegmentum, in the region of the left medial longitudinal fasciculus (fig 2).2 This is highly suggestive of an acute posterior circulation infarct.3 Diffusion weighted imaging provides a visual representation of the freedom for water to diffuse through tissue, with hyperintensities (bright white lesions) reflecting areas of restricted diffusion. In acute stroke, this is caused by ischaemia related disruption of energy metabolism, which leads to abolition of transcellular ionic gradients and translocation of water into the intracellular compartment.4
Fig 2 Diffusion weighted image showing a small area of restricted diffusion in the left upper pontine tegmentum (box labelled 1), in the region of the left medial longitudinal fasciculus
Diffusion weighted imaging is particularly sensitive (88-100%) and specific (86-100%) for the detection of hyperacute and acute ischaemic stroke,4 when early computed tomography is often negative. Diffusion weighted imaging is therefore routinely used for differentiating acute stroke from other processes that manifest with sudden neurological deficits, especially in posterior circulation lesions.5 Restricted diffusion associated with acute ischaemia can be imaged within minutes of the event, and hyperintensities remain for up to four weeks after an infarct.
3. What are the differential diagnoses? Short answer
In older patients with vascular risk factors, internuclear opthalmoplegia is most commonly caused by a vascular brainstem lesion, with an infectious process affecting the brainstem less likely. In younger patients, multiple sclerosis should be suspected; in such cases internuclear opthalmoplegia is often bilateral.
Long answer
The most common causes of internuclear opthalmoplegia are vascular lesions (brainstem infarctions), which made up 37% of causes in one long term follow-up study,6 multiple sclerosis (32%), and infectious diseases (14%). Other causes include head trauma, tumours of the brainstem and fourth ventricle (including pontine gliomas in very young people), inflammatory encephalitis affecting the brainstem, Arnold-Chiari malformation, hydrocephalus, and systemic lupus erythematosus.7 Bilateral disease in young people is almost pathognomic for multiple sclerosis, with unilateral disease in older people or those with vascular risk factors probably being indicative of posterior circulation stroke.
4. How should this condition be managed further? Short answer
Secondary prevention should be initiated, including anticoagulation for atrial fibrillation with a novel oral anticoagulant. The patient should also be referred to occupational therapy and orthoptic services to aid rehabilitation of any persistent visual deficit.
Long answer
Visual complications are common after stroke, with impairment in eye alignment and movement affecting 68% of patients in one study.8 Such complications can interfere with rehabilitation and return to independence in activities of daily living.9 Options for treating diplopia after stroke include visual retraining therapy; occluding one eye, either completely or over the region creating diplopia only; or use of optic prisms. Strabismus surgery can be performed if orthoptic input does not improve diplopia in the longer term. Atrial fibrillation is a major risk factor for ischaemic stroke. The National Institute for Health and Care Excellence (NICE) recommends warfarin as the first line thromboprophylactic agent in those with cardiovascular risk factors,10 11 although dosing and monitoring can be complicated and adverse drug reactions do occur. NICE has approved several novel oral anticoagulants with a similar efficacy and safety profile to those of warfarin in patients who cannot tolerate warfarin (the direct thrombin inhibitor dabigatran, and direct factor Xa inhibitors rivaroxaban and apixaban).12 Draft guidelines suggest an increasing role for these drugs as first line prevention.
Patient outcome The patient recovered most of her visual function. Carotid Doppler ultrasound was normal and echocardiography showed no definitive thrombus, so it was presumed that this was a cardioembolic stroke secondary to atrial fibrillation. After being started on anticoagulation with dabigatran because of a CHA2DS2-VASc score for stroke risk in atrial fibrillation of 6, she was discharged home after occupational therapy input, with follow-up by the orthoptic service in clinic. Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: None. Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent obtained. 1 2 3 4 5 6 7 8 9 10
For personal use only: See rights and reprints http://www.bmj.com/permissions
Keane JR. Internuclear ophthalmoplegia: unusual causes in 114 of 410 patients. Arch Neurol 2005;62:714-7. Atlas SW, Grossman RI, Savino PJ, Schatz NJ, Sergott RC, Bosley TM, et al. Internuclear ophthalmoplegia: MR-anatomic correlation. AJNR Am J Neuroradiol 1987;8:243-7. Kim JS. Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction. Neurology 2004;62:1491-6. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology 2000;217:331-45. Van Everdingen KJ, van der Grond J, Kappelle LJ, Ramos LM, Mali WP. Diffusion-weighted magnetic resonance imaging in acute stroke. Stroke J Cerebr Circ 1998;29:1783-90. Bolaños I, Lozano D, Cantú C. Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand 2004;110:161-5. Obuchowska I, Mariak Z. [Internuclear ophthalmoplegia—causes, symptoms and management.] Klin Oczna 2009;111:165-7. Rowe F, Brand D, Jackson CA, Price A, Walker L, Harrison S, et al. Visual impairment following stroke: do stroke patients require vision assessment? Age Ageing 2009;38:188-93. Jones SA, Shinton RA. Improving outcome in stroke patients with visual problems. Age Ageing 2006;35:560-5. National Institute for Health and Care Excellence. Atrial fibrillation. CG36. 2006. http:// guidance.nice.org.uk/CG36.
Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g3286 doi: 10.1136/bmj.g3286 (Published 19 May 2014)
Page 3 of 3
ENDGAMES
11 12
Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994;343:687-91. Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS, et al. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention
of venous thromboembolism: systematic review and network meta-analysis. BMJ 2013;347:f5133.
Cite this as: BMJ 2014;348:g3286 © BMJ Publishing Group Ltd 2014
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
