Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Georgios Rigakos, MD; Chrysoula I. Liakou, MD; Naillid Felipe, Dennis Orkoulas-Razis, MHS; Evangelia Razis, MD, PhD

Disclosures

Cancer Control. 2017;24(1):9-21. 

In This Article

Clinical Presentation

Pathogenesis of Symptoms

Neoplastic meningitis has a variable clinical presentation with multifocal and multilevel CNS involvement caused by multiple pathophysiological mechanisms, including the mass effect of tumor presence in the subarachnoid space, direct invasion of the leptomeninges and brain parenchyma, CSF circulation obstruction leading to increased intracranial pressure, and cranial or spinal nerve root impingement.[8]

The types of symptoms in neoplastic meningitis arise because of involvement of the different anatomical areas and may, at times, depend on the type of primary cancer. A normal reduction of CSF circulation and the effect of gravity may be why CSF obstruction is seen in the lumbar region and may explain why gross tumor involvement is typically present at the base of the brain (basilar cisterns or posterior fossa), the Sylvian fissures, and the cauda equina.[3] Tumor cells can also reach the leptomeninges through the blood or by invasion into the perineural or perivascular spaces and vascular alterations due to tumor growth.[3,9] Parenchymal metastases may be present, but neurological symptoms that cannot be attributed to a single area of the CNS may be the result of neoplastic meningitis; thus, the clinician must have a high index of suspicion.

Patients with neoplastic meningitis subacutely present with symptoms that can emerge over days or weeks and can include multifocal neurological impairment, meningismus with headache, vomiting, and nuchal rigidity.[10] These symptoms may be difficult to attribute to neoplastic meningitis because they are nonspecific. Signs and symptoms of neoplastic meningitis can be categorized according to where the disease manifests within the 3 anatomical areas of the CNS: cerebrum (15%), cranial nerve/brainstem (35%), and spinal cord (60%).[8,10,11] A retrospective study of 187 patients found that 34% of study patients had signs in 1 anatomical area, 39% in 2 anatomical areas, and 25% in all 3 anatomical areas. Two percent of those study patients had no clinical features,[10] although other researchers have shown that an even higher percentage of patients are asymptomatic.[12]

In all anatomical areas combined, the most common symptoms are headache, nausea, vomiting, paresis, paralysis, confusion, diplopia, cerebellar dysfunction, and back pain (Table 1).[3,6,8–10,12–18]

Cerebral Symptoms

Cerebral symptoms include headache, dizziness/vertigo, confusion, fatigue, gait instability, aphasia, altered mental status, seizure (although rare), hemiparesis, and numbness.[16,19,20] Of these, headache is the most common among all 3 anatomical areas of the CNS.[16,19,20] These symptoms are attributed to high intracranial pressure and may be associated with papilledema. Headaches are often described as worse when awakening or lying down and can interfere with sleep.[19] Other patients present with seizure and altered mental status.[13,16] Nausea and vomiting represent the most common symptom cluster following headache.[8,16] Symptoms are frequently related to intracranial pressure, either with or without evidence of an actual block to the flow of CSF or direct meningeal irritation. Photophobia can also exist but is rare. Involvement of the pituitary stalk can rarely lead to diabetes insipidus or panhypopituitarism.

Cranial Nerve and Brainstem Symptoms

Cranial nerve and brainstem symptoms include visual disturbances (eg, loss of visual acuity, diplopia), facial muscle weakness, hearing loss, nausea and vomiting, dysphagia and dysarthria, hoarseness, decreased hearing, and facial pain or numbness.[8] A related symptom encountered in breast cancer is that of a "numb" or "frozen chin" (ie, presence of hypesthesia in the chin). Visual loss and ocular mobility deficits with diplopia are the most frequently occurring ocular symptoms.[9]

Cerebellar involvement can cause an unsteady gait, diplopia, ataxia, and falls. Such symptoms are present in 65% of patients; nausea, vomiting, and diplopia are the most frequent symptoms.[8]

Spinal Cord Symptoms

Spinal nerve root involvement may cause lumbar pain, limb paresis or paralysis, bowel and bladder dysfunction, and loss of reflexes that may lead to cauda equina or cauda medullaris syndrome.[8,14,15] Paresis or paralysis was the initial finding in 41% of patients presenting with neoplastic meningitis secondary to breast cancer and is a commonly seen symptom.[8,14,16] At our clinic, 1 patient presented with painful, unprovoked muscle spasms who, after investigation, was diagnosed with neoplastic meningitis.

Physical Examination

Findings on physical examination may reflect the multilevel CNS involvement and typically consist of neurological signs. Neurological examination may show visual loss or ocular motor nerve palsies, with abducens nerve being the most commonly affected followed by oculomotor and trochlear nerves.[5]

Oculomotor nerve palsy causes diplopia accompanied with ptosis and mydriasis, whereas the patient with trochlear palsy diplopia may notice it when descending stairs; abducens palsy causes horizontal diplopia. Facial and trigeminal palsy may cause facial weakness and hypesthesia, and vestibular and cochlear nerve involvement may cause hearing impairment, vertigo, and instability. Lower cranial nerve (IX, X, XI, XII) palsies lead to impaired speech and swallowing.

Findings on neurological examination may also reveal weakness in the extremities, hypesthesia, deficits of higher mental functions with altered mental status (confusion, lethargy, personality changes), gait instability, ataxia and dysmetria in cerebellar tests, and asymmetry in tendon reflexes. Funduscopy may or may not reveal papilledema. Nuchal rigidity and the presence of the Lhermitte sign — although considered to be typical signs — are not common.

Patient performance status is important in the setting of neoplastic meningitis. In a study of leptomeningeal metastases from breast cancer and a study of neoplastic meningitis due to several different primary tumors, researchers found that the median Karnofsky performance status was approximately 70%.[8,16]

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