Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma.

We evaluated the cerebrospinal fluid (CSF) levels of the B-cell activating factor of the tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) in two cases of primary central nervous system B-cell lymphoma (PCNSBL) before and after treatment. One patient achieved clinical remission, and demonstrated decrease in the CSF levels of both BAFF and APRIL after treatment. Meanwhile, the other patient with insufficient therapeutic response showed increase in the BAFF levels despite decrease in APRIL levels. This report suggests that the combination of BAFF and APRIL levels could be useful in estimating the therapeutic efficacy in treating PCNSBL as reliable CSF markers.

An elderly patient presenting with a primary spinal multifocal intradural extramedullary pilocytic astrocytoma: a case report and review of the literature.

BACKGROUND: Pilocytic astrocytoma is a low-grade central nervous system tumor most commonly seen in children. Dissemination from a primary intracranial tumor along the neuroaxis has been described at both presentation and disease progression. However, the development of an intradural extramedullary pilocytic astrocytoma independent of a primary intraparenchymal tumor in an adult patient with no history of pilocytic astrocytoma has rarely been reported. CASE PRESENTATION: A 69-year-old woman presented with progressive myelopathic symptoms and thoracic radicular pain. MRI imaging of the whole spine showed an enhancing intradural extramedullary lesion extending from the cervical cord to T11 causing cord compression. Laminectomies were performed for surgical decompression and histopathology was consistent with pilocytic astrocytoma. Complete staging was done that included imaging of the brain and cerebrospinal fluid cytology. No other tumor was found by these methods. Postoperatively the patient was treated with large field spinal radiation and concurrent chemotherapy followed by adjuvant chemotherapy. She has thus far been clinically and radiographically stable. CONCLUSION: This is a rare case of an adult with multiple spinal pilocytic astrocytomas in an intradural extramedullary location, typically the result of cerebrospinal fluid dissemination of neoplastic cells from a primary intracranial tumor site (i.e. drop metastasis). No conventional primary tumor was identified in this patient, suggesting these tumors may arise from heterotopic gliomas.

A Case of a 4-Year-Old Female with a Primary Spinal Malignancy Presenting with Froin's Syndrome.

We report the case of a 4-year-old female with a primary extradural intramedullary atypical teratoid/rhabdoid tumor (AT/RT) leading to a middle cerebral artery (MCA) infarct and Froin's syndrome. She presented with a 6-pound weight loss over the previous week, as well as a decreased urinary output and an altered mental status. She underwent a brain MRI that revealed a left MCA infarct, mild ventriculomegaly, and bilateral internal carotid artery, M1, and A1 stenosis. An external ventricular drain (EVD) was placed due to increased intracranial pressure. Cerebrospinal fluid (CSF) was analyzed via lumbar puncture that revealed extremely elevated protein. However, CSF sampled from the EVD was completely normal, a phenomenon called Froin's syndrome. The following day, she developed a right MCA infarct. Her grim prognosis was discussed with her family and care was eventually withdrawn. The patient underwent an autopsy which confirmed a spinal AT/RT. To our knowledge, this is the first reported case of stroke and Froin's syndrome as the initial manifestations of a primary spinal AT/RT with a late onset of spinal cord compression due to tumor obstruction.

Antineuronal Nuclear Autoantibody Type 1/Anti-Hu-Associated Opsoclonus Myoclonus and Epilepsia Partialis Continua: Case Report and Literature Review.

BACKGROUND: Opsoclonus-myoclonus syndrome is a rare clinical condition that has been associated with neuroblastoma. There are few reported examples of ANNA-1/anti-Hu antibodies in children with neuroblastoma and opsoclonus-myoclonus, all in children aged less than three years of age. METHODS: We describe the new onset of focal seizures without alteration of consciousness and opsoclonus-myoclonus in an 11-year-old girl with ANNA-1/anti-Hu positivity and a paraspinal ganglioneuroblastoma. A systematic review of the literature of children with ANNA-1/anti-Hu positivity and malignancy was also performed. RESULTS: Fourteen patients were identified, eight of whom had opsoclonus-myoclonus. Although epilepsia partialis continua has been described in association with several neuronal autoantibodies, association with ANNA-1/anti-Hu has not been reported. CONCLUSIONS: We describe epilepsia partialis continua in a child with ANNA-1/anti-Hu antibodies and neuroblastoma. Testing for antineuronal antibodies should be considered in children presenting with either opsoclonus-myoclonus or epilepsia partialis continua.

Complete response and long-term survival of leptomeningeal carcinomatosis from breast cancer with maintenance endocrine therapy.

Leptomeningeal carcinomatosis carries a poor prognosis in breast cancer. Treatment modalities are geared towards tumour molecular characteristics, as well as symptoms and patient performance status. It has previously been postulated that endocrine treatments used for the treatment of metastatic breast cancer do cross the blood-brain barrier and can achieve antineoplastic effects in the central nervous system. We report a case of metastatic breast cancer in a 65-year-old woman who developed leptomeningeal carcinomatosis. She was initially treated with intrathecal methotrexate, which was stopped due to toxicity, followed by maintenance endocrine therapy. She achieved a sustained complete radiological and cerebrospinal fluid cytological response for over 9 years. She eventually passed away of ischaemic bowel unrelated to her cancer.

Atypical teratoid/rhabdoid tumor involving cerebrospinal fluid: a case report.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive tumor of the central nervous system. It is primarily seen in younger age-groups, and the cytomorphology has only been infrequently described. CASE: We present a case of AT/RT arising in the cervical spine of a 6-month-old boy. The cerebrospinal fluid (CSF) cytology and correlating findings are described. The CSF cytomorphologic findings of the AT/RT cells are most notably large cells, eccentrically placed pleomorphic nuclei, prominent nucleoli and, commonly, cytoplasmic inclusions, as well as a second population of smaller mononuclear cells with minimal cytoplasm. CONCLUSION: The cervical spine is a rare site for AT/RT to arise. It is important for pathologists to recognize the cytomorphologic features of AT/RT in the CSF of patients with this tumor to help determine prognosis and disease progression.

Intrathecal betamethasone pain relief in cancer patients with vertebral metastasis: a pilot study.

BACKGROUND: We have reported previously the usefulness of intrathecal betamethasone for pain relief in cancer patients who suffer from intractable pain caused by vertebral metastasis. The mechanism by which betamethasone relieves pain may be related to alterations in cerebrospinal fluid (CSF) concentrations of pro-inflammatory cytokines and prostanoids. METHODS: Thirteen cancer patients with intractable pain caused by vertebral metastasis received 2-3 mg betamethasone in the lumbar subarachnoid space. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and prostaglandin E(2) (PGE(2)) were measured with an enzyme-linked immunosorbent assay (ELISA) and a chemiluminescence enzyme immunoassay. Pain was measured using a numerical pain score (range, 0-10; 0, no pain; 10, worst pain imaginable). RESULTS: Intrathecal betamethasone was associated with a significant decrease in the pain score in six patients. In these cases, the pain score decreased from 6.7 +/- 0.5 (mean +/- standard error of the mean) to 3.3 +/- 0.3 (P < 0.05), and the CSF concentrations of IL-8 and PGE(2) decreased significantly compared with pre-treatment levels (IL-8, 183.3 +/- 21.2 to 116.5 +/- 10.6 pg/ml; PGE(2), 43.8 +/- 10.3 to 14.7 +/- 3.0 pg/ml). There were no significant changes in the CSF concentrations of cytokines and PGE(2) in the remaining seven patients. CONCLUSION: Pain relief with intrathecal betamethasone is related to decreases in the CSF concentration of IL-8 and PGE(2).

Cerebrospinal fluid prostate specific antigen (CSF PSA) in prostate cancer patients with lower spine metastasis.

AIM: In this prospective study, our aim was to investigate the CSF PSA levels and CSF/Serum PSA ratios in patients with prostate cancer with lower spine metastasis. METHODS: The study involved patients with prostate cancer (n = 15), benign prostatic hyperplasia (n = 17) and non-prostatic disease (n = 9). Serum and CSF were obtained prior to spinal anesthesia for urological surgery. Total PSA levels in the serum and CSF were measured by electrochemiluminescence immunoassay. The results were tested statistically using the Mann-Whitney U test. RESULTS: The mean serum PSA levels were 20.36 ng/ml in the prostate cancer patients, 5.37 ng/ml in the BPH patients and 0.76 ng/ml non-prostatic disease. The mean CSF PSA levels in groups were 0.127, 0.051 and 0.027 ng/ml, respectively. The mean CSF PSA/serum PSA ratios in groups were 0.007, 0.018 and 0.042, respectively. This result is statistically significant (P < 0.001). CONCLUSIONS: Although mean serum PSA and CSF PSA levels in the patients with cancer of the prostate and lower spine metastasis are higher than those in the others, the mean CSF PSA/serum PSA ratio is lower. However, clinical usefulness of CSF PSA value and CSF PSA/ Serum PSA ratio can be limited because CSF PSA values are usually very low, and CSF PSA/Serum PSA ratio of 4 prostate cancer patients are as high as 1 BPH patient.

Spontaneous rupture of spinal dermoid cyst with disseminated lipid droplets in central canal and ventricles.

Free fat in the ventricular space is a rare but well recognized complication of ruptured tumour of dermal origin. However, only 1 patient of spontaneous rupture of spinal dermoid tumour with disseminated fat in the central canal and ventricles has been described in the literature. The authors report an extremely rare case of ruptured intraspinal dermoid and passage of free fatty droplets via the patent central canal to the intracranial CSF space. The detailed clinical presentation, radiological findings, and review of the literature are presented. Despite being rarely reported, spinal dermoid cyst can rupture spontaneously, and free fat disseminate into the ventricles, and in extremely rare cases, fat can enter into the central canal. It is underlinerd that a prompt detection, with the help of MRI is essential in cases of spinal dermoid tumour cyst, with sudden deterioration in neurological condition, keeping in mind, the possibility of free fat in the central canal.

Detection of craniospinal dissemination of intracranial germ cell tumours based on serum and cerebrospinal fluid levels of tumour markers.

Nineteen intracranial germ cell tumours treated during the past 11 years were evaluated retrospectively. The tumours were classified into three groups according to the level of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) in serum and cerebrospinal fluid, and the optimal treatment for each group was determined. Group A consisted of patients with normal titres of AFP and HCG, group B of patients with relatively high titres (< 10 times normal), and group C comprised patients with higher titres ( 10 times normal levels). In group A, an appropriate field and dose of irradiation was necessary to prevent craniospinal dissemination. In group B, none of four patients who underwent total or subtotal resection of the tumour had craniospinal disseminatio n or tumour recurrence, whereas dissemination occurred in four further patients, including two who had received radiochemotherapy only, and two who had undergone partial resection of the tumour. While patients in group C had dissemination at the time of initial diagnosis, most patients in group B developed dissemination more than 10 months after initial treatment, suggesting that the type of treatment received as first line therapy is important in patients in this group. The prognosis of patients in group C, however, was unaffected by the priority given to either surgery, radiation or chemotherapy as first line treatment. Craniospinal dissemination can be prevented in patients with germ cell tumours who have a relative increase in levels of AFP and HCG by aggressive removal of the tumours as first line therapy, regardless of the type of adjuvant therapy given.

A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases.

Leptomeningeal metastases (LMs) are common metastatic complications, occurring in at least 5% of patients with disseminated cancer. Cerebrospinal fluid (CSF) cytology remains the standard for diagnosis and assessment of treatment response, but may be inadequate. Our objective was to compare ventricular and lumbar CSF cytology in patients who had cytologically proven LM and were receiving intra-CSF chemotherapy. Sixty patients with LM, positive lumbar CSF cytology documented at diagnosis, limited extent of CNS disease, and no evidence of CSF flow obstruction were treated with a variety of intra-CSF chemotherapies. All patients underwent a single simultaneous ventricular and lumbar CSF sampling (mean volume of CSF per site examined, 10 ml) to assess response to therapy at either 1 or 2 months after treatment initiation. Ventricular CSF cytology was positive in 44 patients (73%), 35 of whom were also positive by lumbar CSF cytology. Lumbar CSF cytology was positive in 45 patients (75%), of which 35 were also positive by ventricular CSF cytology. Samples were negative at both ventricular and lumbar sites in 6 patients (10%). Paired CSF cytologies were discordant in 19 (32%) patients. The lumbar cytology was negative in 9, whereas the ventricular cytology was positive (lumbar false-negative rate of 17%); the ventricular cytology was negative in 10, whereas the lumbar cytology was positive (ventricular false-negative rate of 20%). In the presence of spinal signs or symptoms of LM, the lumbar CSF cytology was more likely to be positive than was the ventricular (odds ratio = 2.86; 95% confidence interval, 0.86-9.56). Conversely, in the presence of cranial signs or symptoms, the ventricular CSF cytology was more likely to be positive than was the lumbar (odds ratio = 2.71; 95% confidence interval, 0.76-9.71). In this cohort of patients, whose LM was documented initially by positive lumbar CSF cytology, ventricular and lumbar CSF samples obtained during treatment had similar false-negative rates, depending on the site of clinical or radiologic disease. This suggests that both lumbar and ventricular sites must be sampled when assessing treatment response. If clinical or radiographic disease is present only at 1 site, then CSF from that site is more likely to be positive than is CSF obtained from the more distant site.

Leptomeningeal metastases: evaluation by gadolinium enhanced spinal magnetic resonance imaging.

BACKGROUND: Leptomeningeal metastases are common in patients with metastatic systemic cancer or certain primary brain tumors. They may be unsuspected clinically and may be missed by cerebrospinal fluid (CSF) cytology. We undertook a retrospective study of the diagnostic value of gadolinium enhanced spinal MR imaging in patients with known or at high risk for leptomeningeal metastases (LM). MATERIAL AND METHODS: Ninety-six gadolinium enhanced MR examinations of the whole spine were performed in 61 patients (26 primary central nervous system tumors, 20 solid tumors and 15 lymphoproliferative neoplasms). All patients had detailed neurological evaluation and concomitant CSF examination. RESULTS: Sixty-one MR's (62%) were positive, mostly in the lumbar spine. MR's were positive in 92% of patients with positive initial CSF cytology and in 60% of patients with negative CSF cytology. The MR examination was positive in 49% of those without clinical findings related to the spinal region. It showed disease beyond the symptomatic level in 42% of patients with spinal symptomatology. Multi-level spinal involvement was present in 57% of positive MR exams. CONCLUSION: Enhanced spinal MR is sensitive for the detection of neoplastic spinal seeding. It detects LM in about 50% of high risk patients with negative initial CSF cytology or no spinal symptoms.

Long-term outcome after removal of spinal neurofibroma.

Spinal neurofibromas are uncommon, comprising approximately 3% of all spinal tumors. They occur both sporadically and in association with neurofibromatosis 1 (NF1; von Recklinghausen's disease). This study presents the clinical characteristics of 32 patients who underwent surgery for symptomatic spinal neurofibromas. Twenty-two of these patients showed clinical signs of NF1. The patients were typically younger (median age 31 years) than those with spinal schwannomas. The tumors were located mainly in the cervical region and tended to grow both extra- and intradurally. Patients with NF1 were prone to develop new spinal neurofibromas. A life-table analysis showed a reduced survival rate for these patients compared to that of the general population.

High-resolution 1H NMR spectroscopy of cerebrospinal fluid in spinal diseases.

Twenty-nine patients with disk herniations, 7 patients with intraspinal tumors, 4 patients with multiple sclerosis and one patient with infection by borrelia have been studied by CT, myelography and/or MR. To gain information on the metabolism of central nervous system disease (CNS), and thus, to improve diagnosis the cerebrospinal fluid (CSF) was studied in all cases using high-resolution 1H NMR spectroscopy at 360 MHz. Seventeen metabolites could be identified in CSF in addition to the usual clinical chemical parameters. As compared to a control group discrimination of tumors from inflammation was possible by means of different metabolites and/or metabolite concentration. The CSF in disk herniations differed in the concentration of acetate from the control group. In CSF of tumors, multiple sclerosis and of infection by borrelia distinct differences in the concentrations of putrescine, citrate, valine, alpha-alanine, acetate, creatinine, glucose, beta-hydroxy-butyric acid, glutamine and creatine have been observed both as compared directly and in comparison to the control group. Thus, high-resolution 1H NMR spectroscopy of CSF gives speedy information on metabolism, since a variety of metabolites, usually examined only in different tests, can be studied in one single step. Thus, high-resolution 1H NMR spectroscopy supports imaging, especially MR, as morphological changes in diseases may be differentiated by means of different metabolite profiles. This assumption needs further confirmation on a prospective study with a larger patient population.

Medulloblastomas in childhood: postsurgical evaluation with myelography and cerebrospinal fluid cytology.

Thirty-one children with medulloblastoma treated at the Children's Memorial Hospital have been evaluated with both postoperative myelography and cerebrospinal fluid (CSF) cytological studies. Computed tomography of the spine following myelography was used in an attempt to increase sensitivity. Each study was done 30 days after radical resection of the posterior fossa tumor, and just prior to the spinal irradiation. Only 3 (9.6%) showed positive results for spinal subarachnoid seeding by both myelography and CSF cytology. In 2 of these patients, preoperative head CT showed evidence of intracranial subarachnoid seedings. The incidence of positive myelographic finding in our series is lower than reported ones, and neoplastic cells are detected in the CSF only when the myelography shows visible disease.

[Normal cerebrospinal fluid findings in spinal tumors--an analysis of 503 cases]. / Normale Liquorbefunde bei spinalen Tumoren--Eine Analyse von 503 Fällen.

Till now almost nothing has been published about normal liquor findings in spinal cord tumours. Out of 503 cases there were normal findings of total proteins and cells in 30 cases (6 per cent). A connection with the severity of the compression-syndrome was not evident. Nevertheless liquor examinations are important in diseases of the medulla spinalis. This is especially useful in the differential diagnostical demarcation of inflammable spinal cord diseases, accompanying reactions or bleedings into the spinal channel.

Characterization of CNS lesions by using high-resolution 1H MR spectroscopy of CSF: preliminary results.

Sixty-six samples of CSF from 66 patients with a variety of diseases, including tumors, arteriovenous malformations, aneurysms, brain infarctions, and lumbar back pain, were studied with 1H MR spectroscopy at 360 MHz. 1H MR spectroscopy offers a simple means to obtain fast information about different metabolites simultaneously. As compared with the control group, which consisted of 19 CSF samples from the same group of 66 patients, but from individuals who had no abnormal findings on neurologic examination, common clinicochemical tests, or neuroradiologic studies, our preliminary results suggest that tumors and hemorrhages may be differentiated by 1H MR spectroscopy. MR peak intensities relative to lactate peak intensity were used as variables in a statistical analysis to determine the significance of individual resonance intensities in predicting CNS abnormalities. The most important factors for diagnosis were analyzed by means of a multivariate general linear hypothesis and a principal component method. The most important factors for predicting CNS abnormalities in the studied diseases were creatinine, glucose, creatine, citrate, protein content, glutamine, amount of cells, and valine. By using this model for discriminant analysis, we could predict hemorrhages correctly in 88% of cases and tumors in 75% of cases. All samples of controls were determined correctly. In cases of brain infarctions, different signals were observed, which may lead to further characterization of such lesions. 1H MR spectroscopy may offer a simple means for further characterizing CNS lesions. However, this needs confirmation by a prospective study, which would include a larger patient population with different diseases.

Burkitt's lymphoma--a correlated light and electron microscopic study on the malignancy in the CSF.

In a sporadic case of primary maxillar Burkitt's lymphoma and secondary spinal epidural dissemination, the massive malignancy in the CSF was investigated by light and electron microscopy. At both levels the CSF tumor cells were strikingly similar, with the undifferentiated lymphoblasts that characterize Burkitt's lymphoma in tissue. However, the starry-sky appearance in the CSF was produced more often by degenerating malignant cells than by histiocytes as classically described in tissue with Burkitt's lymphoma.