Neurologic manifestations of intravascular lymphomatosis

Intravascular lymphomatosis is a rare fatal neoplasm characterized by malignant cells of lymphocytic lineage producing vascular occlusions. The cerebral vasculature is particularly affected. Two patients seen at our institution presented with progressive neurologic deficits including dementia, hemiparesis and myelopathy. Review of an additional 64 reported cases with neurologic involvement indicates that patients developed intermittent fevers, an encephalopathy ranging from acute disorientation to rapidly progressive dementia, and focal signs such as hemiparesis and myelopathy. Common laboratory abnormalities include elevated cerebrospinal fluid protein and a lymphocytic pleocytosis, elevated blood erythrocyte sedimentation rate and serum lactate dehydrogenase. Malignant cells are rarely seen in cerebrospinal fluid, blood or bone marrow. Neuroimaging is usually abnormal with parenchymal lesions seen on cerebral tomography and magnetic resonance imaging along with an occasional meningeal pattern of contrast enhancement. Treatment with corticosteroids, chemotherapy, radiation therapy, or plasmapheresis provided limited benefit. Intravascular lymphomatosis should be considered in the differential diagnosis of unexplained progressive encephalopathy with superimposed focal deficits.     

Diagnosis and treatment of intravascular lymphomatosis

OBJECTIVE: To describe a patient with unusually good outcome of a rare, high-grade lymphoma that often involves the nervous system. DESIGN: Case report. SETTING: University hospital. CASE: A 70-year-old pharmacist first presented with meningoencephalitislike symptoms and 6 months later with acute confusional state followed by complex partial status epilepticus. Diagnosis of intravascular lymphomatosis was made using detection and biopsy of a bilateral adrenal tumor. MAIN OUTCOME AND RESULTS: Polychemotherapy consisting of CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) led to complete remission. The patient's survival time currently exceeds 21/2 years. CONCLUSIONS: The possibility of intravascular lymphomatosis should be considered in adult patients with unclear meningoencephalitic syndrome, acute confusional state, dementia, or other unexplained neurologic conditions with signs of a systemic disease. In intravascular lymphomatosis, as in other high-grade non-Hodgkin lymphomas, CHOP polychemotherapy should be the standard treatment.     

The neurological masquerade of intravascular lymphomatosis

BACKGROUND: Intravascular lymphomatosis (IVL) is an uncommon systemic disease characterized by occlusion of small vessels by malignant lymphomatous cells. Central nervous system involvement usually presents as subacute encephalopathy, dementia, seizures, or multifocal cerebrovascular events. OBJECTIVE: To increase awareness about IVL, an uncommon cause of neurological disease. DESIGN: This is a retrospective case series of 8 pathologically proved cases of IVL with neurological disease. Patients were part of a pathological series collected between April 1962 and October 1998 at Indiana University School of Medicine and the Armed Forces Institute of Pathology, Washington, DC. SETTING: Neurological and neuropathological examinations were performed at tertiary referral hospitals. PATIENTS: Eleven patients were diagnosed pathologically as having IVL, but 3 were not included in this evaluation because of a lack of appropriate clinical information. Of the final sample (n = 8), there were 4 men and 4 women (mean +/- SD age, 62.9 +/- 9.9 years). RESULTS: All 8 patients had focal neurological deficits, 7 had encephalopathy or dementia, 5 had epileptic seizures, and 2 had myelopathy. Death occurred at a mean of 7.7 months (range, 1-24 months) after the onset of symptoms. All patients had elevated cerebrospinal fluid protein levels, 4 had pleocytosis, and 2 had an elevated IgG level in their cerebrospinal fluid. Of the 4 patients who underwent a brain biopsy, 1 was diagnosed as having IVL before death. CONCLUSIONS: Intravascular lymphomatosis is an uncommon disease with a myriad of potential neurological manifestations. Diagnosis requires a high index of suspicion and a pathological examination. If diagnosed early, aggressive chemotherapy is potentially curative, although the overall prognosis remains dismal.     

Illusion of stroke: intravascular lymphomatosis

We describe an unusual case of cerebral intravascular lymphomatosis wherein the patient presented with multiple embolic strokes predominantly in the posterior circulation. Using this case as an illustration, we review the literature of this malignancy, which consists of extranodal diffuse large B-cell lymphoma. For patients with recurrent stroke-like events without cardiac risk factors, the accurate diagnosis requires a high index of suspicion by the neurologist and a brain biopsy specimen demonstrating lymphoma cells within the lumen of cerebral blood vessels. Intravascular lymphomatosis can be treated with systemic chemotherapies, but the response rate and pattern of relapse remain unknown.     

Presentation of intravascular lymphomatosis as lumbosacral polyradiculopathy

A 53-year-old man developed progressive sensory disturbance and weakness in the legs, sphincter disturbance, back pain, systemic symptoms, and pancytopenia. Electrophysiological tests indicated a widespread lumbosacral polyradiculopathy. Spinal magnetic resonance imaging and routine cerebrospinal fluid analysis showed minor nonspecific abnormalities. Bone marrow and liver biopsies showed hemophagocytosis; and polymerase chain reaction of cerebrospinal fluid, bone marrow, and serum suggested active infection with human herpesvirus-6. Autopsy revealed that his neurological symptoms resulted from intravascular lymphomatosis (angiotropic large cell lymphoma), a rare variant of lymphoma with predilection for the nervous system.     

Mitotic activity in cerebrospinal fluid cells

Mitotic figures were observed in 38 cases of a series of 3200 CSF cytograms. Their relative incidence was the highest in cases of tumoural invasion of the CSF, but they also occurred in inflammatory and reactive fluids and did not necessarily indicate tumoural origin. In bacterial infections of the central nervous system they were mainly present during the repair phase of the disease. In haemorrhagic spinal fluid they were absent. These findings suggest that cell division in spinal fluid tends to develop in conditions in which the viability of the cells is not affected by introduction of foreign material such as blood and bacteria.     

Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor

Inhibitory antibody to von Willebrand factor (vWF)-cleaving protease (ADAMTS13) was detected in a patient with intravascular lymphomatosis. The increased serum level of the antibody paralleled an increase in the expression of uncleaved vWF, which might cause microvascular thrombosis and platelet consumption. Malignant cell proliferations with superimposed thrombosis within the lumina throughout the entire vasculature account for diffuse neurodeficits observed in the patient.     

Alpha-naphthyl-acetate-esterase activity in cerebrospinal fluid cells

Mono-histiocytes and T-lymphocytes were assessed by the cytochemical alpha-naphthyl-acetate-esterase (ANAE) stain in 50 CSF samples of patients with various neurological diseases. The ANAE-activity of lymphocytes was decreased in multiple sclerosis and subacute sclerosing panencephalitis, while the activity of mono-histiocytes was increased in the group of infarctions and bacterial and viral infections of the central nervous system. In bacterial meningitis and viral meningo-encephalo-radiculitis the number of ANAE-positive lymphocytes increased after treatment and clinical improvement. ANAE staining appears to be a useful additional tool in CSF cytology in these conditions.     

Signs of rapidly progressive dementia in a case of intravascular lymphomatosis

Intravascular lymphomatosis (IVL), a rare type of non–Hodgkin’s lymphoma, is an uncommon cause of progressive dementia, usually followed by death within a few months of onset of clinical disease. Often this aggressive tumor is only diagnosed at autopsy, because of misleading clinical features mimicking a broad spectrum of syndromes and the absence of circulating lympoma cells in the blood, bone marrow or cerebrospinal fluid in many cases. Here we present IVL in a 78–year–old woman with findings leading to the clinical diagnosis of vascular dementia with sudden beginning and positive 14–3–3 protein in the CSF, commonly reported in Creutzfeldt–Jakob disease (CJD).     

Meningothelial cells participate in immunological processes in the cerebrospinal fluid

Meningothelial cells (MECs) form the innermost layer of the meningeal sheath and as such are in direct contact with the cerebrospinal fluid (CSF) likely influencing CSF composition. The CSF space is a site of active immunological processes. To investigate an immunological role of MECs, cytokine and chemokine secretion, phagocytotic and pinocytotic activity by MECs was analyzed following stimulation with lipopolysaccharide, phorbol ester or rotenone. Secretion of IL-6 and IL-8 by MECs increased in a dose dependent manner after stimulation concomitant with NF-κB activation. In addition, phagocytotic clearance by MECs was enhanced suggesting an immunological role for MECs in the CSF compartment and pointing to a possible connection to neurodegenerative processes.     

Myeloma cells in the cerebrospinal fluid in plasma cell neoplasia

Myeloma cells were detected in the cerebrospinal fluid of two patients with plasma cell neoplasia during the myelographic studies of 38 patients whose myeloma was associated with extensive neurological complications. The myeloma cells were looked for in Wright stained centrifuged deposit of 2–5 ml samples of the cerebrospinal fluid obtained during myelography. The possibility that occult traumatic lumbar puncture had allowed entry of circulating myeloma cells from the peripheral blood into the subarachnoid space was excluded by the absence of myeloma cells in smears of peripheral blood and its buffy coat. Up to the end stages of the disease the meningeal myeloma lesions remained microscopical and no signs of raised intracranial tension were manifested by either patient.