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A 51-year-old woman with binocular diplopia and unilateral ptosis
Digital Journal of Ophthalmology 2019
Volume 25, Number 3
August 18, 2019
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Landon J. Rohowetz, BS | University of Missouri – Kansas City School of Medicine, Kansas City, Missouri
Anjulie K. Quick, MD | Department of Ophthalmology, University of Kansas School of Medicine, Prairie Village, Kansas
Diagnosis and Discussion
Central nervous system (CNS) involvement in AML is rare; therefore, AML patients without signs of CNS involvement do not routinely undergo diagnostic evaluation or prophylactic treatment for CNS involvement. The prevalence of CNS involvement in AML, however, is significantly higher at relapse (2.9%) than at initial presentation (0.6%).(4) CNS involvement is also more common in patients with myelomonocytic or monocytic leukemia.(5) The process by which leukemia spreads to the CNS may involve hematogenous spread or direct extension from cranial bone marrow to the dura and/or leptomeninges, termed leptomeningeal lymphomatosis.(6) Tumor cells that reach the CNS before treatment may be protected from stem cell therapy and chemotherapy by the blood-brain-barrier.(7) CNS recurrence is known to occur in hematologic malignancies after successful chemotherapy because of the presence of the blood-brain barrier, which may protect leukemic cells from the cytotoxic effects of treatment.(8)

Involvement of the bone marrow is usually seen in cases of AML CNS relapse, which occurs more often in those who have not undergone allogenic hematopoietic stem cell transplantation.(9) However, even in cases without bone marrow involvement and with prior stem cell transplantation, suspicion for leptomeningeal metastasis must be high in patients with focal neurologic deficits and a history of leukemia or lymphoma. MR imaging should be obtained but may be normal in 29%-88% of patients with leptomeningeal metastasis.(10-12) Thus, CSF sampling should be performed, because it is more sensitive, with a false negative rate as low as 11% (and lower with repeat sampling).(10,13) Current guidelines recommend CSF studies in conjunction with MRI in the initial workup of a patient with suspected leptomeningeal metastasis.(14-16) Once diagnosed, treatment consists of intrathecal chemotherapy with repeat clinical and CSF evaluation after induction therapy.(15)

To our knowledge, this is the first case of AML presenting as an isolated pupil-involving oculomotor nerve palsy due to leptomeningeal metastasis. Similar cases have been reported, but in those cases either the pupil was spared or other cranial nerves were involved in addition to the oculomotor nerve.(17-20) Furthermore, this is the only oculomotor nerve–involving case of AML relapse in which CNS involvement was not apparent on imaging. While similar manifestations of AML relapse have been described, all cases involving the oculomotor nerve presented with imaging findings correlating with clinically observed neurologic deficits.(17-19) Although our patient’s MRI revealed mild proptosis, signs of oculomotor nerve dysfunction as evident on examination were absent on imaging.

A similar case of abducens nerve–involving AML relapse not apparent on imaging was recently described by Fozza et al.(21) That case parallels the present one insofar as it was in a patient in their first AML remission presenting with CNS relapse manifesting as a cranial nerve palsy in the absence of imaging findings that was ultimately diagnosed with CSF evaluation. Our patient had undergone hematopoietic stem cell transplantation, though, whereas the patient reported by Fozza et al had not, making our case somewhat more atypical, because CNS relapse is less common after stem cell transplantation.(9) Moreover, their patient presented with bilateral abducens nerve deficits and systemic symptoms characteristic of intracranial hypertension, including nausea, vomiting, and dizziness. The abducens nerve is particularly susceptible to elevated intracranial pressure, and as such it is possible that generalized intracranial hypertension was the cause of the patient’s deficits rather than localized leptomeningeal invasion, as suspected in our patient, who only presented with an isolated, unilateral oculomotor nerve palsy and fatigue. Both patients illustrate the range of potential presentations and the importance of CSF evaluation in the assessment of a patient with suspected AML CNS relapse.

Literature Search
PubMed was searched on December 9, 2019, without date or language restriction, using the following terms, singly and in combination: acute myeloid leukemia AND leptomeningeal metastasis, oculomotor nerve, oculomotor nerve palsy, relapse, or third nerve palsy; oculomotor nerve OR oculomotor nerve palsy AND cancer, etiology, leukemia, leptomeningeal metastasis, and leptomeningeal lymphomatosis.