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A 56-year-old man with acute vision loss
Digital Journal of Ophthalmology 2016
Volume 22, Number 3
August 18, 2016
DOI: 10.5693/djo.03.2015.05.006
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Fani Akritidou | General Hospital of Kavala
Maria Karafyloglou | General Hospital of Kavala
Dimitrios Karamanis | General Hospital of Kavala
Diagnosis and Discussion
The MRI and CT results, combined with a negative laboratory work-up for other possible causes of optic disc edema and the development of neurological symptomatology, led to the decision to perform a lumbar puncture. CSF analysis confirmed the diagnosis of meningeal carcinomatosis, because the examination was positive for malignant cells and dysplastic/atypical cells were present.

Meningeal carcinomatosis is a rare condition, but it is associated with devastating complications and high mortality. Ocular involvement is a frequent and early clinical manifestation of meningeal carcinomatosis and may mimic different diseases. Our patient manifested optic disc edema as the first sign of meningeal carcinomatosis. The exclusion of the most common causes of optic nerve head swelling, his medical history, and the close monitoring led to an early diagnosis of this condition.

Meningeal carcinomatosis should be included in differential diagnosis and CSF analysis should be requested in any patient with ocular symptoms when the most common causes of ocular symptomatology are excluded, especially in patients who have a known history of malignancy.

Meningeal carcinomatosis is defined as a diffuse infiltration of the meninges by metastatic cancer.(3,4) It is the first manifestation of systemic cancer in only 5%-10% of patients, although it is frequently seen in patients with disseminated systemic disease.(5,6)

Hematologic tumors are the most frequent cause of meningeal carcinomatosis, particularly acute lymphoblastic leukemia and non-Hodgkins lymphoma.(5) The incidence of clinically diagnosed meningeal carcinomatosis in patients with solid tumors is approximately 5%, but the incidence of undiagnosed or asymptomatic meningeal carcinomatosis may be higher.(7) Although any cancer can metastasize to the leptomeninges, breast cancer (12%-35%), lung cancer (10%-26%), melanoma (5%-25%), gastrointestinal cancer (4%-14%), and cancers of unknown primary origin (1%-7%) are the most common causes of solid-tumor-related meningeal carcinomatosis.(6-8)

Neoplastic cells may spread to the subarachnoid space through arterial circulation or, less frequently, through retrograde flow in venous systems or as a direct consequence of preexisting brain metastasis or through migration of neoplastic cells from the original tumor along perineural or perivascular spaces.(9-11) Clinical presentation is highly variable and may affect both central and peripheral nervous system. It is usually organized into three categories: cerebral, cranial nerve, and spinal.(6) Central nervous system involvement may lead to generalized symptoms such as seizures, confusion, encephalopathy, or intracranial hypertension as well as, less frequently, focal neurological symptoms, mainly consisting of hemiparesis or aphasia; peripheral nervous system involvement may present with lumbar and cervical radiculopathies or cranial neuropathies.(7,9) The most common manifestation of cranial nerve involvement is diplopia due to abducens nerve palsy, followed by oculomotor and trochlear nerve involvement. The trigeminal and vestibulocochlear nervew may also be affected.(9,12)

Ocular involvement represents a frequent manifestation of meningeal carcinomatosis.(13,14) Visual impairment as an important component of the syndrome received little attention in ophthalmological and neurological literature until 1955, when Fischer-Williams et al reported that partial or complete blindness occurs in one-third of such patients.(15,16) In 1961 Katz et al in a review of the neuro-ophthalmological findings of meningeal carcinomatosis, described decreased vision in 44% of cases.(17,15) The most common ocular manifestation was visual loss (70%), followed by diplopia (41%), ptosis (19%), papilledema (10%), anisocoria (7%), exophthalmos (5%), orbital pain (5%), scotomas (5%), hemianopsia (2%) and nystagmus (2%).(9)

The exact mechanism by which meningeal carcinomatosis produces visual impairment is not well defined. The implicated mechanisms could be direct infiltration of the optic nerve, tumor cuffing of the leptomeninges with compression of the nerve, compromised vascular supply, humoral toxin, or retinal photoreceptor degeneration as a remote effect of cancer. Some cases, however, remain inadequately explained by any of these mechanisms.(18-20)

Because ocular involvement is a frequent and early clinical manifestation of meningeal carcinomatosis and may mimic different diseases, early diagnosis is challenging. Clinical suspicion of the condition is based on the finding of neurological signs and symptoms at more than one level of the neuraxis. Multifocal neurological symptoms and signs are strongly suggestive of the diagnosis of meningeal carcinomatosis in patients with known cancer, but patients may also present with isolated and subtle neurologic symptoms.(7)

Currently, the diagnostic approach includes neuroimaging studies (cranial and spinal CT and MRI), which allow identification of the pathological process eventually involving the leptomeninges, and CSF analysis. Although the presence of malignant cells in CSF is the pathognomonic laboratory examination for meningeal carcinomatosis, the sensitivity of this test is suboptimal. Wasserstrom et al reported that the sensitivity of single lumbar puncture is only 54%, and 91% sensitivity could be achieved with repeated tests.(8,10,14)

The diagnosis of meningeal carcinomatosis may be ascertained according to the National Comprehensive Cancer Network guidelines.(21) The guidelines suggest that any one of the following diagnostic criteria are sufficient to diagnose meningeal carcinomatosis; CSF positive for tumor cells (positive CSF cytology); radiologic findings in the central nervous system consistent with meningeal carcinomatosis irrespective of supportive clinical findings or alternatively and more controversial, clinical signs and symptoms consistent with meningeal carcinomatosis, and a nonspecific but abnormal CSF analysis (high white blood cell count, low glucose <60 mg/dl, and elevated protein >50 mg/dl) in a patient known to have a cancer.(4,7)

Although meningeal carcinomatosis occurs in only 3%-8% of all cancer patients, it is associated with devastating neurologic complications and high mortality.(10) The median survival of patients with this disorder is 4-6 weeks without treatment; even in response to therapy, median survival in these patients is limited to 18.6 weeks.(7,22)

Early diagnosis is important, although treatment is intended to reduce the symptoms and at best extend survival, especially when neurologic symptoms are already present.(5) Because there are no well-established regimens, the treatment of meningeal carcinomatosis varies, and treatment options are very limited. Options are intrathecal (IT) chemotherapy, radiotherapy, and best supportive care. IT chemotherapy is the mainstay of treatment because it is a more selective and relatively less toxic. Methotrexate, cytosine arabinoside, and thiotepa in combination with hydrocortisone are the most frequently used drugs, although there are other substances tested in several clinical trials.(5,10,14)

Treatment is only palliative and cannot provide lasting clinical benefit for the majority of cases. Patients with meningeal carcinomatosis have a guarded prognosis with a mean survival rate of 3-6 months.(4,5,22)