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Amaurosis fugax as the presenting symptom of metastatic lung adenocarcinoma

Published:October 18, 2018DOI:https://doi.org/10.1016/j.jcjo.2018.08.012
      An 80-year-old Caucasian female with a remote history of nonarteritic ischemic optic neuropathy of the left eye presented with transient vision loss in the right eye, occurring once or twice per week, for the month before presentation. The onset of each episode was abrupt, rather than gradual, and described as “things fading in the right eye,” and “objects looking duller than usual” over the entire visual field. She had no positive visual phenomena with these episodes, which often lasted approximately 1–5 minutes. Each episode was neurologically isolated, without headache or focal neurologic symptoms. After each episode, the vision slowly returned to her previous baseline. She identified no precipitating factors related to her symptoms.
      She had a negative review of systems, including fevers, chills, weight loss, fatigue, headache, jaw claudication, scalp tenderness, weakness, numbness, vertigo, diplopia, oscillopsia, slurred speech, facial droop, chest pain, palpitations, dyspnea, cough, or hemoptysis.
      Examination at presentation was notable for a visual acuity of 20/40 OD and count fingers OS, as well as a left afferent pupillary defect, which was unchanged from baseline with her left ischemic optic neuropathy. Intraocular pressures were 14 mm Hg OU. Slit-lamp and fundus examination of the right eye showed no anterior segment disease, vessel occlusion, Hollenhorst plaques, or other retinal or vascular abnormalities. Her temporal artery pulses were strong bilaterally and she had no scalp tenderness. She had no other focal neurologic defects and the rest of her physical examination was unremarkable.
      She was hospitalized for urgent evaluation of transient monocular vision loss. Laboratory work-up was notable for a troponin elevation, as well as mild anemia, thrombocytopenia, and hyponatremia. Erythrocyte sedimentation rate and C-reactive protein were unremarkable. Head computed tomography (CT) was negative for intracranial hemorrhage. Brain magnetic resonance imaging (MRI) was obtained and revealed multiple punctate cortical and juxtacortical areas of diffusion restriction, involving all vascular territories (Figure 1).
      Fig 1
      Fig. 1Diffusion-weighted sequences of brain magnetic resonance imaging showing multiple, punctate areas of hyperintensity in the bilateral hemispheres (A) and posterior fossa (B).
      Carotid Dopplers showed smooth plaques in the internal carotid arteries causing less than 50% stenosis, but were otherwise unremarkable.
      Given the involvement of multiple vascular distributions, a trans-thoracic echocardiogram was performed, which was negative for valvular abnormalities or right-to-left shunt. A trans-esophageal echocardiogram was then performed, which showed characteristic mobile echodensities on both leaflets of the mitral valves, including a 6 × 5 mm lesion on the posterior leaflet and 4 × 1 mm lesion on the anterior leaflet, without significant regurgitation or valve destruction (Figure 2). Blood cultures were obtained and negative for bacterial or fungal growth.
      Fig 2
      Fig. 2Trans-esophageal echocardiogram showing mobile echodensities. LA, left atrium; PMVL, posterior mitral valve leaflet; AMVL, anterior mitral valve leaflet; LV, left ventricle. Arrow, posterior leaflet vegetation; arrowhead, anterior leaflet vegetation.
      A CT of the chest, abdomen, and pelvis was performed that showed spiculated lesions in the lingula and right upper lobe of the lung, as well as mediastinal lymphadenopathy.
      Positron emission tomography–CT showed increased uptake in the spine, pelvis, sternum, and thoracic wall, consistent with metastatic osseous disease. An ultrasound-guided biopsy of a paratracheal lymph node was performed. Pathology revealed malignant cells, strongly positive for thyroid transcription factor (TTF-1) and NapsinA, consistent with metastatic pulmonary adenocarcinoma.

      Discussion

      “Transient monocular vision loss” (TMVL) is a broad term used to describe sudden, nonpermanent vision loss in one eye. The etiology of TMVL comprises a wide range of ophthalmic, neurologic, and systemic disease. Commonly, “amaurosis fugax” is the term used when TMVL is secondary to vascular insufficiency or ischemia.
      The Amaurosis Fugax Study Group
      Current management of amaurosis fugax.
      The causes of amaurosis are extensive and include both embolic and thrombotic etiologies.
      • Pula JH
      • Kwan K
      • Yuen CA
      • Kattah JC
      Update on the evaluation of transient vision loss.
      Identifying the cause is of critical importance in the correct diagnosis and subsequent management of the underlying condition.
      In this case, we believe that the patient's symptoms were attributable to an embolic source, from nonbacterial thrombotic endocarditis (NBTE) associated with metastatic lung adenocarcinoma. Anterior segment and dilated fundus examination findings were normal, not supporting retinal or other ocular pathologies, including intermittent angle closure glaucoma or ocular surface disease. Carotid Dopplers were negative for clinically significant stenosis or plaque rupture. There were no cardinal symptoms of giant cell arteritis, and inflammatory markers were within normal limits. She also had no history of migraine, and the characteristics of the episodes, including the frequency and duration, would be unusual for retinal migraine or migraine aura with headache. Indeed, many cases of the so-called retinal migraine are vascular in origin.
      • Hill DL
      • Daroff RB
      • Ducros A
      • Newman NJ
      • Biousse V
      Most cases labeled as “retinal migraine” are not migraine.
      NBTE is a rare condition that refers to noninfectious vegetations of cardiac valves, most commonly associated with advanced malignancy or autoimmune disease. Rates in autopsy series range from 0.6% to 1.6%.
      • Gonzalez Quintela A
      • Candela MJ
      • Vidal C
      • Roman J
      • Aramburo P
      Non-bacterial thrombotic endocarditis in cancer patients.
      • Llenas-Garcia J
      • Guerra-Vales JM
      • Montes-Moreno S
      • Lopez-Rios F
      • Castelbon-Fernandez FJ
      • Chimeno-Garcia J
      Nonbacterial thrombotic endocarditis: clinicopathologic study of a necropsy series.
      It is characterized by deposition of sterile platelet-fibrin thrombi, immune complexes, and mononuclear cells, most frequently on the mitral or aortic valves.
      • Eiken PW
      • Edwards WD
      • Tazelaar HD
      • McBane RD
      • Zehr KJ
      Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985–2000.
      The pathogenesis is thought to be related to endothelial injury caused by circulating cytokines in the setting of a hypercoagulable state.
      • Dipasco PJ
      • Misra S
      • Koniaris LG
      • Moffat Jr, FL
      Thrombophilic state in cancer, part I: biology, incidence, and risk factors.
      Vegetations associated with NBTE are particularly prone to embolization, due to the relative lack of inflammation at the site of attachment, and can cause multiple embolic events.
      • Roldan CA
      • Sibbitt Jr., WL
      • Qualls CR
      • et al.
      Libman-Sacks endocarditis and embolic cerebrovascular disease.
      Initial evaluation is with transthoracic echocardiography (TTE) but transesophageal echocardiography (TEE) has increased sensitivity for small vegetations.
      • Dutta T
      • Karas MG
      • Segal AZ
      • Kizer JR
      Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia.
      Characteristically, vegetations associated with NBTE are typically small, <1cm in diameter, broad based, and not associated with overt destruction of valve tissue or positive blood cultures,
      • Asopa S
      • Patel A
      • Khan OA
      • Sharma R
      • Ohri SK
      Non-bacterial thrombotic endocarditis.
      as in this case.
      Hypercoagulability disorders as a group are rare as the initial presentation of occult malignancy. Furthermore, NBTE as the presenting sign of occult malignancy is rarely reported in the literature.
      • Lee JM
      • Lim JH
      • Kim JS
      • et al.
      Multiple hypercoagulability disorders at presentation of non-small-cell lung cancer.
      • Orfanelli T
      • Sultanik E
      • Shell R
      • Gibbon D
      Nonbacterial thrombotic endocarditis: a rare manifestation of gynecologic cancer.
      Amaurosis fugax as the presenting symptom of NBTE associated with lung adenocarcinoma has not been previously reported.
      There is increasing evidence that silent cerebral ischemia can accompany episodes of thromboembolic TMVL, highlighting the importance of a comprehensive investigation for an embolic source.
      • Helenius J
      • Arsava EM
      • Goldstein JN
      • et al.
      Concurrent acute brain infarcts in patients with monocular visual loss.
      In particular, diffusion-weighted MRI can guide work-up, because ischemic strokes in multiple distributions suggest a cardioembolic source. Carotid sources of TMVL are more common than cardiac emboli, but consideration of a cardiac source is important when clinical suspicion is high. TEE is more sensitive in identifying small lesions and can be pursued when TTE is negative, as in this case. In our case, the discovery of NBTE led to the diagnosis of lung adenocarcinoma. In cases where there are no obvious traditional causes of amaurosis, NBTE should be considered, even in the absence of a history of malignancy or hypercoagulability.

      Appendix. Supplementary materials

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