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We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.

We reacted dispersed cultures of newborn rat cerebellar granule cells with serum, purified IgG, and CSF from patients with type IIa ("anti-Hu") antibody response accompanying paraneoplastic neurologic syndromes. All type IIa sera, IgGs, and CSFs, but not those of normal or cancer controls, produced bright nuclear immunofluorescence of cultured granule neurons. Type IIa serum and CSF labeled proteins of 35-42 kd in rat granule cell blots, identical in molecular weight to proteins labeled by type IIa antibodies in blots of human granule cells. IgGs eluted from the 35-42 kd band in blots of rat granule cells labeled proteins of similar molecular weights in blots of human granule cells and produced typical type IIa immunostaining of human cerebellar sections. Human IgG could be identified in nuclei and cytoplasm of neurons incubated for 72 hours with 2/4 type IIa sera tested, but not with normal sera. Type IIa sera or IgGs from 4/7 patients produced specific lysis of rat granule cells in the presence of complement, as compared with controls using normal serum or heat-inactivated complement. Prolonged (7-day) incubation of cultures with type IIa antibody without complement also resulted in specific lysis, whereas incubation with normal serum or serum from neurologically normal patients with small-cell carcinoma of the lung did not. Rat granule cell cultures provide a valuable in vitro system with which to study the interaction of type IIa antibody with neurons. The present study provides the first reported evidence that type IIa antibodies may cause cell injury directly, in the absence of lymphocyte-mediated immune response.

A 61-year-old woman presented with two paraneoplastic neurologic disorders--Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD)--that antedated the diagnosis of small-cell carcinoma of the lung by 15 months. Plasmapheresis initiated before the identification of the tumor had a beneficial effect on LEMS but did not affect the SCD. Chemotherapy administered for treatment of the primary tumor was also associated with improvement of LEMS but, like plasmapheresis, had no effect on SCD. While the pathogenesis of both LEMS and SCD is thought to be mediated predominantly by humoral immune factors, a differential therapeutic response indicates that mechanisms of tissue damage or susceptibility to tissue injury, or both, differ in these two disorders.

We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity "primary leptomeningeal lymphoma" (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis.

Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH.

We studied 85 cancer patients with lumbosacral plexopathy and documented pelvic tumor by CT or biopsy. Three clinical syndromes were delineated: lower (L4-S1), 51%; upper (L1-L4), 31%; and pan-plexopathy (L1-S3), 18%. Seventy percent of patients had the insidious onset of pelvic or radicular leg pain, followed weeks to months later by sensory symptoms and weakness. The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer. CT showed pelvic tumor in 96%. On myelography, epidural extension, usually below the conus medullaris, was seen in 45%. With treatment, only 28% of patients had objective responses on CT and 17% on examination.

Several groups of investigators have confirmed the occurrence of antibodies to Purkinje and other cerebellar neuronal populations in the serum and spinal fluid of patients with paraneoplastic cerebellar degeneration. Although this antibody response suggests that paraneoplastic cerebellar degeneration may have an autoimmune basis, it is not known what role anticerebellar antibodies play in the pathogenesis of this disorder or whether the presence of antibodies invariably results in cerebellar injury. We identified 3 patients with ovarian malignancies in whom high titers of circulating anticerebellar antibodies were present without clinical evidence of cerebellar disease. We followed these patients clinically and serologically until their deaths from their neoplasms. All 3 patients remained neurologically normal. In 2 of the patients, anticerebellar antibodies persisted at high titer. CSF obtained from 1 of these patients postmortem did not contain detectable levels of anticerebellar antibody, but histopathologic examination of her cerebellum revealed patchy loss of Purkinje cells. In the 3rd patient, antibody titers fell with removal of the primary tumor and chemotherapy but did not rise with tumor recurrence. Indirect immunofluorescence did not reveal anticerebellar antibodies in the serum or CSF of other patients with neoplasms, patients with other cerebellar disease, or normal controls. The present study demonstrates that patients with ovarian malignancies may occasionally develop antibodies that react with cerebellar neuronal antigens and can maintain this antibody response for protracted periods of time without clinically evident cerebellar injury. Tumor recurrence may not be accompanied by rise in titers of anticerebellar antibodies.