Download Acute Cranial Nerve VI Palsy Secondary to Paraneoplastic Syndrome

Acute Cranial Nerve VI Palsy Secondary to Presumed Paraneoplastic
Syndrome
Brittany McNeely, O.D.; Anthony Van Alstine, O.D., M.S., FAAO
Abstract:
Complex cancer patient presents with acute onset diplopia and severe headache. Ocular
examination reveals isolated cranial nerve VI palsy OS. After thorough workup, paraneoplastic
syndrome is the most likely etiology.
I. Case History
1) Patient demographics: 69 year old Native American male
2) Chief complaint: Sudden onset diplopia and new, severe headache in the orbital and temporal
region OS for 3 days
3) Ocular history: Negative. The patient had a completely normal eye exam 3 weeks prior to
presentation.
4) Medical history: The patient has a history of colon cancer with metastasis to the lung
evidenced on CT. At the time of presentation, the patient was not undergoing treatment with
chemotherapy. Despite prior chemotherapy treatment with Folfiri and Panitumumab, the
pulmonary mass was continuing to enlarge as evidenced on serial CT exams. The patient also
had rising CEA-mono levels, indicating increased antigen secretion by the tumor. A new
chemotherapy treatment regimen was to be initiated in the coming weeks. The patient also has a
history of Hypertension, Hyperlipidemia, Cholecystitis, and Anemia.
5) Medications: Lorazepam, Loperamide, Ondasetron, Aspirin, Hydrochlorothiazide, Losartan,
Ibuprofen
6) Other salient information: This patient has no history of diabetes, and his hypertension had
been well-controlled with systemic medication over the last several months. The patient reported
the worst headache of his life surrounding the left orbit and temporal region. History was
positive for malaise, but negative for jaw claudication and painful palpation of the temporal
artery. The patient was taking a reprieve from chemotherapy due to significant cutaneous side
effects and general improved well-being without chemotherapy.
II. Pertinent findings
1) Clinical: Presenting VA was 20/25+ OD and 20/20 OS. Pupil testing was normal.
Extraocular motility testing and cover test revealed a cranial nerve VI palsy OS. The patient did
not report a significant increase in pain with abduction OS. Anterior segment findings were
unremarkable. Posterior segment examination revealed a healthy retina and normal optic nerves.
2) Physical: The patient reported the worst headache of his life, and the patient’s affect was
consistent was consistent with this complaint.
3) Laboratory studies: Following presentation in the eye clinic, ESR and CRP were ordered to
rule out giant cell arteritis. Both the ESR and CRP were slightly elevated, with an ESR of 35
mm/hr and CRP of 1.44mg/dL. Hemoglobin A1c was 5.9. Blood pressure reading was slightly
elevated at 146/86 mmHg. Over the next several days, extensive laboratory tests were ordered.
CBC showed elevated lymphocytes and granulocytes. MRSA screening, ANA, and Rheumatoid
factor were negative. Urinalysis and Thyroid testing with TSH and T3 were normal. CEA-mono
levels had elevated significantly from 2.84 to 3.33 over the previous 6 weeks. Previously, the
CEA-mono level had been steadily increasing by 0.1-0.2 every 2-3 months or remaining stable
between measurements.
4) Radiology studies: MRI studies showed no compressive etiology of the brain or orbits. Chest
X-ray showed a mass in the left lung measuring 3.2mm x 2.9mm. Previous mass measurement
was 3.1mm x 2.8mm 6 weeks prior. The tumor had been steadily increasing in size since
diagnosis 9 months prior.
5) Others: Ophthalmology and Thoracic Surgery were consulted for a potential temporal artery
biopsy due to the patient complaint, location of the pain, cranial nerve VI palsy, and slightly
elevated ESR and CRP. It was determined that artery biopsy would be performed if imaging and
further lab testing showed no other etiology for the presentation.
The patient was admitted to the hospital the day after presentation due to dizziness while
at the hospital for further evaluation. During his stay, the patient was evaluated extensively by
Neurology. MRI and CT showed no brain or orbit malformations, and all other testing for
ischemic and compressive etiology was normal. Rapid CEA-mono elevation, indicating rising
cancer enzymes, was the only significant change in the patient’s medical history. The patient did
not have a history of recent illness or any other new neurological symptoms. While ESR and
CRP were slightly elevated, the patient has a history of complex cancer, and the levels were not
elevated to sufficient levels that would indicate Giant Cell Arteritis. As a result, the temporal
artery biopsy was deemed unnecessary and cancelled. The neurologist indicated the etiology was
presumed paraneoplastic syndrome due to the complex cancer history, the absence of ischemic or
mass etiology, and the rapid increase in CEA-mono measurements. Laboratory testing for
paraneoplastic antibodies is pending. The presence of paraneoplastic antibodies can be used to
confirm a diagnosis paraneoplastic syndrome; however, literature review indicates that less than
50% of patients with paraneoplastic syndrome will test positive for antibodies. As a result, the
absence of these antibodies cannot rule out paraneoplastic syndrome. Lumbar puncture to
evaluate elevated white blood cell count can also aid in the diagnosis; however, at this time, the
patient has postponed chemotherapy and declined invasive procedures.
III. Differential diagnosis
1) Primary/leading: Post viral etiology. However, the patient has no recent history of illness.
2) Others: Giant Cell Arteritis, malignant neoplasm of the brain or orbit, vasculopathy from
Hypertension
IV. Diagnosis and discussion
Elaborate on the condition:
1) Paraneoplastic syndrome is a group of syndromes in which there are neurological
abnormalities as a result of a benign or malignant tumor. These syndromes specifically refer to
neurological deficits in cancer patients that are not related to metastasis, infection, or side effects
of treatment. Paraneoplastic syndromes most commonly result from an immune response to
enzymes released by a primary mass, and they can affect any part of the neurological system. In
some cases, the patient may not have a formal cancer diagnosis at initial presentation, and
paraneoplastic syndrome may be the presenting sign of malignancy. While hematology can
reveal antibodies to certain cancer enzymes, over 50% of patients with paraneoplastic syndrome
will have no related antibodies found on laboratory testing. As a result, diagnosis is most
commonly made based on the patient complaint and clinical presentation. Paraneoplastic
syndromes are most common in lung cancer, ovarian cancer, breast cancer, and Hodgkin’s
disease.
Because any part of the nervous system can be affected by paraneoplastic syndrome,
neuro-ophthalmologic findings can be common in this condition. Neuro-ophthalmologic findings
can include cranial nerve palsies, opsoclonus, myoclonus, nystagmus, gaze palsies, pupil
abnormalities, and optic neuropathy. There are several different mechanisms that can result in
neuro-ophthalmological symptoms; however, the most common etiology is encephalitis.
2) Expound on unique features: Cranial nerve VI palsy of uncommon cause in a complex cancer
patient with evidence of mass progression with CT and rising cancer enzymes. Most cranial
nerve VI palsies are due to ischemic etiology from uncontrolled diabetes or hypertension. Less
commonly, these palsies can arise from an intracranial or intraorbital mass or viral etiology.
Cranial nerve palsies due to the immune reaction to cancer enzymes in paraneoplastic syndromes
are rare, with few cases reported in the literature.
V. Treatment, management
1) Treatment and response to treatment:
The patient was prescribed Hydrocodone/APAP to help with his headaches, and the patient
was given an eye patch to alleviate diplopia. Oncology was consulted due to presumed
paraneoplastic etiology. Lab results for paraneoplastic antibodies are pending. At this time, the
oncologist has decided to defer treatment due to patient request. The patient has further
evaluation with oncology in 1 month, with complete blood work and CT exams. The cranial
nerve palsy will continue to be monitored in Optometry for resolution and possible prismatic
correction if the palsy does not resolve.
2) Research/Literature review/ Bibliography
Ko, M.W., Dalmau, J., Galetta, S.L. Neuro-Ophthalmologic Manifestations of Paraneoplastic
Syndromes. J Neuro-Opthalmol. Vol 28., No 1., 2008
Flemmons, M.S., Schiffman, J.S. Cranial Nerve III, IV, and VI palsies in the Cancer Patient.
Ophthalmic Oncology. M.D. Anderson Solid Tumor Oncology Series: 6. 2010
Hammon, T.H., McFadzean, R.M., Ironside, J.W. Anti-Hu Paraneoplastic Syndrome Presenting
as Bilateral Sixth Cranial Nerve Palsies
VI. Conclusion
Most cases of cranial nerve VI palsies can be attributed to ischemic etiology, intracranial
mass, or intraorbital mass. However, it is critical to consider paraneoplastic syndrome in patients
with a known history of cancer, or in the absence of ischemic or mass etiology.