| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (T.M.B., J.D.B., A.A.R., J.H.U.), Radiology (J.H.), and Neurosurgery (G.L.), Mayo Clinic College of Medicine, Rochester, MN.
Address correspondence and reprint requests to Dr. Joseph D. Burns, Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905 Burns.Joseph{at}mayo.edu
 |
SECTION 1 |
|---|
 Top. SECTION 1 SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
Further questioning revealed additional symptoms. After the first episode of altered consciousness, his personality changed. His wife described him as "vacant" and "not as active and happy-go-lucky" as usual. He developed a slowly progressive, mild dysarthria; difficulty walking due to frequent "buckling" of the right knee; and numbness in the right medial forearm and little finger. He also described difficulty in using his hands to perform tasks such as putting toothpaste on a toothbrush, which he described as being like "putting two magnets together." Finally, he had lost about 25 pounds over the preceding 3 months.
In addition to the childhood seizures, his past medical history was notable for a fungal infection of the lung in 1997 for which he had been admitted to an intensive care unit. The details of this illness were not known beyond the fact that he was treated for several months with an antibiotic. He had a remote smoking history.
Questions for consideration: 1. What is the differential diagnosis for this clinical presentation?
2. What features of the history are most useful in narrowing the differential diagnosis?
|
SECTION 2 |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
Equally crucial to formulating a neurologic differential diagnosis is to begin to localize the disease process within the nervous system from the history. Doing so allows one to narrow the list of possible etiologies. This patient's clinical syndrome points to a multifocal or diffuse disease process. Complex partial seizures localize to the frontal or temporal lobe. While the long duration of the event and the postictal period suggests a temporal lobe focus, it is impossible to precisely localize the seizure focus in this case solely from the history. The personality change suggests dysfunction of anterior portions of the frontal lobe, caudate nucleus, or the anterior thalamus, while the difficulty with hand coordination suggests a cerebellar or parietal lobe lesion. Numbness in the medial right arm and little finger suggests a lesion of the ulnar nerve or C8 root, while the knee buckling may localize to the femoral nerve, lumbar roots, thoracic spinal cord, or medial left frontal lobe. Without further semiologic characterization, the dysarthria could localize to a number of structures and therefore is of little localizing value.
On examination, the patient was afebrile and had normal vital signs. He was thin and appeared chronically ill. There was no meningismus. The remainder of the general medical examination was unremarkable. On neurologic examination, he was listless, somewhat inattentive, and seemed unconcerned with his illness. The cranial nerves were normal and there was no papilledema. Motor examination revealed a right pronator drift and a low-amplitude, high-frequency action tremor in the arms. Muscle stretch reflexes were normal with the exception of brisk knee reflexes. Plantar responses were equivocal on the right and extensor on the left. Pinprick sensation was reduced on the medial aspect of the right hand, including the little finger. Sensation of light touch and vibration as well as cortical sensory function were normal. There was no appendicular ataxia.
Questions for consideration: 1. Based on the history and examination, what is your clinical formulation?
2. What diagnostic tests would be useful to test this hypothesis?
|
SECTION 3 |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
While other localizations are possible, this combination of findings best localizes simultaneously to the frontal lobe cortex and the meninges. When considered along with the history of weight loss and remote history of a fungal lung infection, likely etiologies include subacutely progressive meningoencephalitides such as those caused by fungi and mycobacteria, autoimmune inflammatory conditions, and neoplastic processes such as lymphoma and metastatic carcinoma. To narrow this list down, imaging and CSF analysis are necessary.
Results of complete blood count, electrolytes, renal function, and coagulation studies were normal. C-reactive protein and erythrocyte sedimentation rate were not elevated and testing for antinuclear and antineutrophil cytoplasmic antibodies as well as rheumatoid factor was negative. Blood cultures and serologic testing for numerous fungi, HIV, and syphilis were negative. The purified protein derivative test was nonreactive. CT of the chest, abdomen, and pelvis were unremarkable.
Brain imaging revealed a lesion in the anteroinferior right frontal lobe. The CT examination without contrast showed a hypodense mass with a thin, slightly hyperdense rim. On MRI (figure), the lesion was heterogeneous, with mixed T1 and T2 signal intensity. The center had increased signal on both T1 and T2 sequences, while the rim was hypointense on T1 and T2. There was mild, heterogeneous enhancement along the lesion's rim and diffuse leptomeningeal enhancement. The gradient echo sequence revealed increased susceptibility artifact primarily along the rim. Diffusion-weighted imaging displayed restricted diffusion in the center of the lesion.
|
MRI of the spine with contrast can be helpful in distinguishing among inflammatory, infectious, and neoplastic diseases and can provide valuable anatomic information. For example, focal enhancing lesions of the leptomeninges at the right C8 nerve root would be supportive of a multifocal neoplastic process and would confirm the findings of our history and physical examination. However, because the patient's severe headaches were provoked by supine positioning and his condition was rapidly deteriorating, a spine MRI was not performed.
CSF was obtained by lumbar puncture performed after brain imaging. The opening pressure was 360 mm H2O and the unspun fluid was yellow and viscous. After centrifugation, xanthochromia was present. The protein level was 1,991 mg/dL and the glucose concentration 48 mg/dL. Although a simultaneous serum glucose was not checked, it was never less than 100 mg/dL during the entire admission. The erythrocyte count was 13/µL and there were 34 leukocytes/µL (34% lymphocytes, 42% monocytes, 4% atypical cells). There was no evidence of malignant cells on cytology and flow cytometry. No organisms were apparent on the gram stain or fungal smear, and cultures for bacteria, fungi, and mycobacteria as well as PCR for herpes simplex virus, Epstein-Barr virus, cytomegalovirus, and varicella zoster virus were negative.
Question for consideration: 1. How does the information provided by the imaging and CSF analysis help your diagnostic process?
|
SECTION 4 |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
The signal characteristics of the lesion on MRI provide important information. The T2 hypointense rim is caused by hemosiderin, while the high T1 and T2 signal intensity in its center is indicative of subacute blood. The subacute blood is also responsible for the restricted diffusion. This combination of findings can be seen in a relatively limited number of conditions, including cavernous malformations, arteriovenous malformations, subacute intracerebral hemorrhages, contusions, abscesses, and tumor (primary or metastatic). The intense enhancement of the leptomeninges on the postcontrast images indicates the presence of leptomeningeal inflammation. The combination of hemorrhage and restricted diffusion with diffuse leptomeningitis further narrows the list of possible etiologies to the following: abscess with associated meningitis (bacterial, fungal, or mycobacterial), focal tumor with diffuse neoplastic meningeal infiltration (metastatic tumors from a variety of tissues, lymphoma, or glioblastoma), infarct or hemorrhage with associated meningitis (primary CNS vasculitis, systemic vasculitis with CNS involvement, or meningovascular syphilis), or a focal inflammatory mass with associated meningitis (sarcoidosis).
The highly elevated protein level, slightly low glucose concentration, mild lymphocytic-monocytic pleocytosis, and elevated opening pressure found on CSF analysis are all indicative of an inflammatory process, providing support to the differential diagnosis formulated on the basis of the clinical and imaging findings. However, due to the absence of a more specific finding, such as identification of a pathogen or malignant cells in the fluid, these results do not help to narrow down the list of possible diagnoses.
Question for consideration: 1. Are any other useful diagnostic tests available for this patient?
|
SECTION 5 |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
Dexamethasone 2 mg every 6 hours was started once the pathologic diagnosis was made. The patient's postoperative course was unremarkable. He was transferred to a hospital closer to his home on postoperative day 6 and was scheduled to begin treatment with whole brain radiation and temozolomide 4 weeks after the resection. However, his health declined precipitously after transfer, and he died 4 weeks later.
|
DISCUSSION |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
Autopsy studies have shown that as many as 20% of patients with high-grade cerebral gliomas have leptomeningeal metastases.3,4 Only approximately 4% of patients with supratentorial malignant gliomas, however, exhibit symptoms referable to this process.5 Furthermore, meningeal metastases from glioblastomas most often present late in the course of the disease, after the primary tumor has been diagnosed.6 Few cases have been reported in which meningeal metastases were responsible for the presenting symptoms in patients with glioblastomas.7 Interestingly, younger patients with glioblastomas may be at relatively higher risk for this secondary leptomeningeal seeding.3,4
Meningeal metastatic disease from glioblastomas responds poorly to radiation or chemotherapy and carries a grave prognosis. The average survival after the onset of symptoms due to meningeal involvement was 2–3 months in one study.6 These survival data are derived largely from patients in whom meningeal disease was a late manifestation and therefore may not apply to patients in whom meningeal disease manifests early in the course of the disease.
When clinically apparent, leptomeningeal metastases from glioblastomas most often cause a syndrome similar to subacute meningitis with headache, confusion, and neck and back pain.4,7,8 A wide variety of focal neurologic symptoms can be seen, the most common being cranial nerve palsies, radiculopathies, and myelopathy. These symptoms are probably caused by infiltration, mass effect, and inflammation at the sites of leptomeningeal tumor deposits.8 In addition, symptomatic hydrocephalus can occur.4,8 Finally, a vasculopathic syndrome with multifocal infarctions caused by occlusion of small, leptomeningeal-based blood vessels encased by tumor cells has been described.8
The CSF in patients with leptomeningeal metastases from a glioblastoma is typically abnormal, with a lymphocytic pleocytosis, elevated protein, and sometimes hypoglycorrhachia.7 CSF cytology, however, is negative in more than 50% of patients.5 Staining cells found in the CSF for glial fibrillary acidic protein may increase the diagnostic yield of cytology when gliomatosis is suspected.9 Imaging findings associated with glioblastoma leptomeningeal metastases include hydrocephalus, periventricular and leptomeningeal enhancement, and sulcal effacement.10 Unfortunately, with the exception of cytology, none of these findings clearly differentiates glioblastoma leptomeningeal metastases from other causes of subacute meningitis.
The rarity and nonspecific nature of its clinical, laboratory, and imaging manifestations makes the diagnosis of leptomeningeal metastases from glioblastoma difficult when a primary tumor is not apparent. As illustrated by this case, this difficulty can be overcome by the use of a disciplined diagnostic approach that includes systematic consideration and synthesis of all elements of the case, including the history, physical examination, laboratory, and imaging data. Finally, this case demonstrates the utility of brain biopsy when less invasive diagnostic modalities have failed to confirm a diagnosis.
*Dr. Burrus and Dr. Burns contributed equally.
Disclosure: The authors report no disclosures.
|
REFERENCES |
|---|
|
Top.SECTION 1SECTION 2SECTION 3SECTION 4SECTION 5DISCUSSIONREFERENCES |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
