Diagnosis Of Central Nervous System Involvement Research Articles

Clinical Course of Adult T-Cell Leukemia-Lymphoma with Central Nervous System Involvement

Background: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma with a highly diverse clinical presentation. Although central nervous system (CNS) involvement is common, the detailed clinical presentation of CNS-ATL needs to be clarified. Objective: This study aims to clarify the clinical course of ATL with CNS involvement. CNS involvement was classified according to the criteria of JALSG202 for acute lymphocytic leukemia as follows: Grade I: no symptoms and cerebrospinal fluid (CSF)cell count less than 5/μl and presence of abnormal lymphocytes; Grade II: asymptomatic and CSF cell count 5-50/μl and presence of abnormal lymphocytes; Grade III: symptomatic or CSF cell counts > 50 cells/μl and presence of abnormal lymphocytes. Results: The analysis included 213 cases of ATL treated at Kagoshima University Hospital from 2002 to 2021. Of these aggressive ATL cases, the clinical subtypes at initial presentation were as follows: acute type 109, lymphoma type 54, chronic type 30, smoldering type 18, and 2 cases were unclassifiable. The median age of the patients was 63 years, and 96 cases (45.1%) were women. Sixty patients had received allogeneic hematopoietic stem cell transplants. During the clinical course, 28 patients (13.1%) with a median age of 61 years and 13 women（46.4%）had CNS involvement. Two cases were classified as Grade I, six as Grade II, and 20 as Grade III. Among them, nine patients (4.2%) showed neurological symptoms at the initial ATL diagnosis, and 1 patient presented with neurological findings at the time of chronic to acute transformation. Of the remaining 203 patients, prophylactic intrathecal chemotherapy was administered in 101 cases, at which time CNS involvement was diagnosed in 9 cases (8.9%). Three patients developed symptomatic involvement while responding to chemotherapy. One patient developed symptomatic involvement when refractory to chemotherapy. Four cases were CNS recurrence with systemic disease progression after remission. Two cases were identified as primary CNS-ATL. The simplified ATL-PI (Prognostic Index) at initial ATL diagnosis for the 28 patients with CNS involvement revealed four cases with high-risk, thirteen with intermediate-risk, two with low-risk, six not eligible due to indolent ATL subtypes, and three cases with unknown risk. The incidence of CNS involvement by ATL subtype was 17.8% (19/107) for acute type, 1.8% (1/54) for lymphoma type, 16.7% (5/30) for chronic type, and 0% for smoldering type (excluding 1 case of unknown subtype and 2 cases of primary CNS-ATL) at ATL diagnosis. At the diagnosis of CNS involvement, 15 (53.6％) patients showed at least 5% of ATL cells in the peripheral blood. During a median observation period of 429 days, the 1-year cumulative incidence of CNS involvement was 12.3% (95% CI 8.3-17.1%). High-dose methotrexate-based therapy was administered to 5 patients with CNS involvement, which had a certain effect on CNS lesions but had limited efficacy for other lesions. All of these cases were treated with concomitant intrathecal chemotherapy. The 2-year overall survival rate after diagnosis of CNS involvement was 16.9% (95% CI 4.9-35.2%). The CNS-IPI (International Prognostic Index) did not predict CNS involvement in ATL. Conclusions: This is the largest study to examine the clinical course of CNS involvement of ATL. The 1-year cumulative incidence of CNS involvement was 12.3%, indicating that CNS involvement is an early complication after diagnosis of aggressive ATL, especially in leukemic subtypes. The prognosis after the diagnosis of CNS involvement was also clarified. The high frequency of CNS involvement during prophylactic intrathecal chemotherapy in patients with ATL without neurological symptoms suggests that it is an important clinical question that needs to be addressed.

Is flow cytometry useful in determining central nervous system involvement in patients with hematological malignancy? Analysis with a prospective cohort

Central nervous system (CNS) involvement occurs in approximately 5–15% of patients in hematological malignancies. Early diagnosis and treatment is essential for a successful approach to CNS involvement. The gold standard method for diagnosis is cytological evaluation, but its sensitivity is low. Flow cytometry (FCM) from cerebrospinal fluid(CSF) is another method used to identify small groups of cells with abnormal phenotype. In our study, we compared FCM and cytological findings in the evaluation of CNS involvement in our patients with hematological malignancies. 90 patients [58 males, 32 females] were included in the study. CNS involvement was positive in 35(%38.9) patients, negative in 48(%53.3) patients, and suspicious (atypical) in 7(%7.8) patients by flow cytometry and ıt was positive in 24(%26.7) patients, negative in 63(%70) patients, and atypical in 3(%3.3) patients by cytology. While the sensitivity and specificity were found to be respectively 68.5% and 100% by cytology, it was found to be 94.2% and 85.4% by flow cytometry. Flow cytometry, cytology and MR findings were significantly correlated with each other in both prophylaxis (p < 0.001) and patients with prediagnosis of CNS involvement. Although the gold standard diagnostic method in the diagnosis of CNS involvement is cytological, its sensitivity is low and it can give false negative results at a rate of 20–60%. Flow cytometry is an ideal objective and quantitative method for identifying small groups of cells with abnormal phenotype. Flow cytometry can be used routinely in the diagnosis of CNS involvement in patients with hematological malignancies with cytology, since it can detect fewer malignant cells, has a higher sensitivity, and provides easy and faster results.

Extremely high levels of central nervous system involvement in miliary tuberculosis

BackgroundMiliary tuberculosis (TB) is one of the severest manifestations of TB that can be lethal when concomitant with the central nervous system (CNS) involvement. Bacteriological, biochemical and radiological methods for find CNS comorbidity in miliary TB was evaluated in this study.MethodsConsecutive miliary TB adults were retrospectively enrolled from two designated TB hospitals in China. The capacities of examinations of cerebrospinal fluid (CSF), cerebral computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis of CNS involvement were assessed.ResultsAssessment of CNS involvement with a lumbar puncture and/or neuroimaging was undertaken in 282 out of 392 of acute miliary TB. Of these 282 patients, 87.59% (247/282) had CNS involvement. Cerebral contrast-enhanced MRI (96.05%, 170/177) and MRI (93.15%, 204/219) yielded significantly higher sensitivities over CSF examination (71.92%, 146/203, P < 0.001) and CT (34.69%, 17/49, P < 0.001). The sensitivity of CSF examination was superior to CT scan (P < 0.001). Although 59.65% (134/225) miliary TB patients acquired bacteriological evidence with sputum examination, the positivity was only 8.82% (21/238) for CSF examination by conventional and molecular tests.ConclusionAlmost all miliary TB had CNS involvement and MRI demonstrated outstanding potential over other methods. Therefore, a routinely screening of CNS TB should be strongly suggested in miliary TB and MRI could be used as the initial approach in resources rich settings.

Central Nervous System Involvement in Extranodal Natural Killer/T-Cell Lymphoma: Case Series

▪Introduction：Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is an aggressive subtype of non-Hodgkin lymphoma that is characterized by extranodal presentation. Central nervous system (CNS) involvement in NKTCL is very rare and carries dismal outcome, but lacks clear consensus on optimal treatment. This study summarized the clinicopathological features, treatment patterns and survival outcomes of NKTCL patients with CNS involvement, in order to improve the understanding of CNS involvement in NKTCL.Methods: 1019 patients diagnosed with extranodal NKTCL, from August 2010 to January 2021 were reviewed, and patients with CNS involvement were included in the analysis. The CNS involvement was diagnosed either pathologically or clinically. Due to the difficulties and potential hazards of brain biopsy, pathologic confirmation of CNS involvement was conducted by identifying malignant cells in the cerebrospinal fluid (CSF) by cytology and flow cytometry analysis. Clinically diagnosed CNS involvement was based upon the characteristic radiographic findings by magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET/CT), Circulating EBV-DNA was detected by quantitative polymerase chain reaction (PCR). Overall survival (OS) was defined as time from confirmation of CNS disease to death from any cause or last follow up.Results: Among 1019 patients diagnosed with NKTCL, 14 cases (1.3%) with CNS involvement were included. The general characteristics of these patients are listed in Table 1. Of these 14 patients, the median age was 40.5 years (range, 14-57 years) at the time of diagnosis of CNS involvement. Approximately 71.4%(10/14）of patients were men. The median time between initial diagnosis of NKTCL and diagnosis of CNS involvement was 3.0 months (range, 0-141.0 months). 5 patients suffered CNS involvement at initial diagnosis of NKTCL. The other 9 CNS involvement were identified as disease progression. All patients underwent radiological examination, which disclosed the lesion location in CNS of 9 patient. The other 5 patients were diagnosed with CNS involvement by the examination of CSF. The elevated protein concentration and leukocytosis in CSF were identified in 8 and 2 patients, respectively. Among these patients with CNS involvement, the median number of treatment lines after the diagnosis of CNS involvement was 1.5 (range, 1-4). The best response was complete response (CR) in 11 patients, partial response (PR) in 1 patient, stable disease in 1 patient and progressive disease in 1 patient. CR was achieved when patients were treated with pegaspargase- containing regimens(n=4), anti-PD-1 antibodies-containing regimens(n=3), chidamide-containing regimens(n=2) and HD-MTX-containing regimens(n=2). After achieving CR, 2 patients received anti-PD-1 antibodies as maintenance treatment, with the duration of response of 26 and 72 months, respectively. With the median follow-up of 24.5 months (range, 4-72 months), 5 patients died of NKTCL, and the median OS was not reached. 9 patients presented with high circulating EBV-DNA level at diagnosis of CNS involvement, and the post-treatment EBV-DNA descended to the normal level in 7 patients, among whom 6 patients achieved CR.Conclusions: The incidence of CNS involvement in NKTCL is low. Compared with previous studies, more patients received anti-PD-1 antibodies- and chidamide-containing regimens, which may contribute to the improved response rate and survival outcomes. Measurement of dynamic changes in EBV-DNA levels during the treatment process can be applied to monitor the treatment response. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract P3-08-41: Central nervous system metastases in breast cancer: The impact of age on patterns of development and outcome

Abstract Background: Breast cancer is the second most common cause of central nervous system (CNS) metastasis, leading to a significant decrease in survival rate. High risk groups for CNS involvement include younger age, human epidermal growth factor 2 (HER2) over-expression, estrogen receptor (ER) and progesterone receptor (PR) negativity, high histologic grade, and presence of systemic metastases. Young age at diagnosis of breast cancer is associated with more aggressive biological behavior and worse prognosis than in the elderly. However, data are limited regarding CNS involvement in this group of patients. Although it could be expected that younger patients would also have a poor prognosis after the diagnosis of CNS metastases, earlier studies have demonstrated conflicting results, some with favorable outcomes for this unique group. In this study we aimed to explore the differences in the patterns and outcome of CNS involvement according to age at diagnosis of breast cancer (≤45 years vs. &amp;gt;45 years). Methods: A retrospective database of consecutive breast cancer patients who were treated in our institute and were diagnosed with CNS metastases during 2006-2019 was generated. Data analyzed included age at diagnosis of breast cancer, age at diagnosis of CNS involvement, histopathological factors (histology, grade, hormone receptor and HER2 status), treatments given before and after CNS involvement, characteristics of CNS involvement (location, number of brain deposits, clinical manifestations), overall survival, time to CNS progression, and survival after diagnosis of CNS disease. Results: Study cohort was comprised of 174 patients: 65 patients were age≤45 and 109 patients were older than 45 at breast cancer diagnosis. The percentage of patients with triple-negative breast cancer was higher among the younger age group (24.6% vs. 14.7%). Median overall survival from breast cancer diagnosis was significantly longer for younger patients [117.1 months (95% CI 67.2-167) vs. 88 months (95% CI 65.6-110.4), p=0.017]. Median time from breast cancer diagnosis to development of CNS metastases was also significantly longer in the younger age group [58.1 months (95% CI 46.5-69.6) vs. 37.5 months (95% CI 22.9-52.2), p=0.021]. Median survival as measured from time of CNS involvement was 18.7 months (95% CI 10.8-26.6) in the younger group vs. 11.1 months (95% CI 7.8-14.5) in the older patients (p=0.341). Survival of patients with triple-negative breast cancer from time of CNS metastases diagnosis was significantly longer for the younger age group [22.5 months (95% CI 1.2-43.8) vs. 7.9 months (95% CI .77-15.1), p=0.033]. The number, location and clinical presentation of CNS metastases were not statistically different between the two groups. Systemic and CNS-directed treatment approaches were also similar. Conclusion: While the presentation of CNS metastasis was similar between the different age groups, younger patients had significantly longer CNS-free interval and longer overall survival. Numerically, after diagnosis of CNS involvement younger patients had longer survival, but the difference was statistically significant only for patients with triple-negative disease. Citation Format: Matan Ben-Zion Berliner, Shlomit Yust-Katz, Inbar Lavie, Alexandra Amiel, Dalia Zoref, Daniel Hendler, Hadar Goldvaser, Michal Sarfaty, Ofer Rotem, Olga Ulitsky, Tali Siegal, Victoria Neiman, Rinat Yerushalmi. Central nervous system metastases in breast cancer: The impact of age on patterns of development and outcome [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-41.

CHRONIC LYMPHOCYTIC LEUKEMIA INVOLVEMENT OF CENTRAL NERVOUS SYSTEM: A SINGLE CENTRE EXPERIENCE

Introduction: Chronic lymphocytic leukemia (CLL) involvement of central nervous system (CNS) is reported to be rare, mainly due to only occasional appear of predominantly non-specific neurological symptoms. Neurologic complications arising from direct leukemic involvement of CNS is stated in only 1% of patients (pts) with CLL. There is no treatment consensus with similar results of intrathecal chemotherapy or whole-brain irradiation, but some more recent studies reported more encouraging data with application of immunochemotherapy or tyrosine kinase inhibitor, ibrutinib. CLL with CNS involvement is related with poorer outcome, especially for pts with unfavorable cytogenetic (17p deletion). Methods: We presented a small series of four pts that were diagnosed and treated in our Institution. All pts met the International Workshop on CLL diagnostic criteria (2008). Diagnosis of CNS involvement was established via neuroimaging methods such as MRI, as well as cerebrospinal fluid (CSF) cytology, and CSF multiparameter flow cytometry immynophenotyping method (CSF FCM). Results: All pts were men with average age of 55.25 years (yrs). On CNS onset, all had disseminated disease and 17p deletion was registered in one case. Average latency period from CLL to CNS onset was 2.91 yrs. We registered heterogeneous neurological symptoms on CNS onset, including bradypsyhia, headaches, nausea, vomiting, dysphasia, repeated unconsciousness, urinary incontinence, dyslexia, lack of fine motor control, diplopia and bilateral eyelid swelling. Diagnostics included positive CSF cytology in three cases, CSF FCM was performed in all of our cases. MRI scan was performed in all cases and was conclusive in three (75%) cases. On CLL onset, two pts were treated with systemic chemotherapy, FC (fludarabine, cyclophosphamide) in one case and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisolone) in other, third was initially treated with corticosteroid therapy due to immunological thrombocytopenia and fourth was on “watch and wait” policy, due to comorbidities. Two of our pts were treatment naïve on CNS onset. When CLL in CNS was diagnosed, systemic chemotherapy was applied in all cases. First patient received high-dose methotrexate with intrathecal therapies, second R(rituximab)-FC, and two received DHAP regimen (dexametasone, high-dose cytarabine, cisplatin) in two cases. Average and median OS from CNS onset was 4 and 3.5 months, respectively, with lethal outcome in 75% of cases in our follow-up. Conclusions: CLL in CNS is still rarely diagnosed, primarily due to the presence of heterogeneous, non-specific neurological symptoms, or their absence. The most effective diagnostics includes MRI, CSF-FCM, and if it is possible PCR detection of CLL cells in CSF. Our results confirm the poor therapeutic outcome and short survival in our group of pts. Keywords: chronic lymphocytic leukemia (CLL); flow cytometry; immunochemotherapy.

Immunophenotyping of the cerebrospinal fluid as a prognostic factor at diagnosis of acute lymphoblastic leukemia in children and adolescents

ABSTRACTThis study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p < 0.0001) and event-free survival (p < 0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.

Secondary Central Nervous System (CNS) Involvement in Patients Diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) during the First Line R-CHOP Treatment and after the End of Treatment

Background: Secondary central nervous system (CNS) involvement is an unfavorable risk factor with an impact on overall survival (OS) in malignant lymphoma.Methods: We conducted a retrospective analysis of secondary CNS involvement in patients diagnosed with Diffuse Large B-Cell lymphoma (DLBCL) on the first line treatment and after the end of treatment. We collected data on 361 patients diagnosed with DLBCL.Results: The median age (range) was 66 (17-91) years. All patients received first-line R-CHOP21 (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) between 2006-2011. Patients with primary involvement of testis, nasopharynx, orbit and CNS received CNS prophylaxis with 15 mg methotrexate intrathecally (IT). Secondary CNS involvement was confirmed in 18 (4.9%) patients which stands for 24.6% (18/73) patients with relapsed lymphoma. Median time from first R-CHOP to lymphoma relapse was 10 months (range 3-33). CNS involvement in first 12 months of treatment was 3.9% (95% CI: 1.8%, 5.8%). Median (range) OS from diagnosis of CNS involvement was 3 (3-79) months. Clinical stage III/IV, IPI 4, breast, 2 or more extranodal sites and NCCN-IPI unfavorable site involvement increased the risk of CNS involvement. Three patients who had received methotrexate IT prophylaxis had CNS involvement at relapse. No patient with primary testis involvement had CNS relapse.Conclusion: Less than 5% of patients had secondary CNS involvement on first line treatment and after end of treatment. Advanced stage, high-risk IPI, 2 or more extranodal sites of involvement increased the risk of CNS involvement after first-line treatment for DLBCL. CNS prophylaxis appears effective in patients with primary testicular lymphoma DisclosuresWalewski:Karyopharm: Consultancy; Roche: Consultancy, Honoraria, Other: travel, accommodation, Research Funding; Celgene: Honoraria, Other: travel, accommodation, Research Funding; Gilead: Consultancy, Honoraria, Other: travel, accommodation; Takeda: Consultancy, Honoraria, Other; Ariad: Consultancy; Janssen-Cilag: Consultancy; Mundipharma: Consultancy, Honoraria, Research Funding; Genetics: Other: travel, accommodation; Teva: Consultancy, Honoraria; Seattle: Other: travel, accommodation; GSK/Novartis: Research Funding; Boehringer Ingelheim: Consultancy; Sanofi: Honoraria, Other: travel, accommodation; Servier: Consultancy.

370P - CNS Metastases, Subtypes and Survival in Breast Cancer: A Population Based Study in Eastern Switzerland

ABSTRACT Purpose To examine tumor characteristics and outcomes associated with central nervous system (CNS) metastases in patients with metastatic breast cancer (MBC). Methods Patients listed in the regional cancer registry of St. Gallen-Appenzell with MBC between 2003-2009 were included. Estrogen- (ER), progesterone receptor (PR) and HER2 status were collected from pathology reports. Biologic subtypes were approximated using standard immunohistochemical markers. Survival status was assessed in January 2012. Multivariate logistic regression models were used to identify factors associated with the risk of developing CNS metastases and with survival >12 months (mt) after the diagnosis of CNS involvement. Results Overall, CNS metastases were observed in 170 (22%) of 773 patients with MBC included in the study. In the multivariate model, factors associated with CNS metastases were age 12 mt. Conclusion Patients with TN or HER2-positive tumors showed increased risk for CNS metastases. However, after diagnosis of CNS metastases only surgery and radiotherapy favorably influenced survival. New approaches to control CNS disease in young patients with these subtypes need to be developed. Disclosure All authors have declared no conflicts of interest.

Fatal consequences of an ear infection

In August, 2006, a 75-year-old non-diabetic, non-alcoholic man with hypertension and atrial fi brillation was ad mitted to the Internal Medicine department with low grade fever, increasing otalgia, otorrhoea, dysphagia, and hoarseness. He had suff ered from bilateral tympanic membrane perforation, intermittent otalgia, and otor rhoea for 12 years. In May, 2006, his otolaryngologist had prescribed ofl oxacin ear drops and oral ciprofl oxacin for otalgia and otorrhoea. In June, 2006, he was admitted to the Ear, Nose and Throat department with a 3-week history of left peripheral facial nerve palsy, left trigeminal sensory loss, and general discomfort. He was afebrile, with a serum C-reactive protein concentration of 72 mg/L; other laboratory tests were normal. CT and MRI of the head showed clouding of the left mastoid without intra cranial pathology or menin geal enhancement (fi gure A); chest radiography was normal. A diagnosis of mastoiditis was made, and ceftazidime and fl ucloxacillin were started. Surgical exploration of the left mastoid showed granulation tissue in the external auditory canal and around the ossicles. Microscopically this tissue showed chronic-active necrotising infl ammation; cultures (in cluding those for fungi) were negative. After 2 weeks, the patient was discharged in fair condition. In the current admission, besides earlier described cranial nerve dysfunction, a partial left glossopharyngeal and vagal nerve palsy were diagnosed by the consulting oto laryngologist. C-reactive protein was 57 mg/L with normal white cells. Culture of discharge from the ear grew Pseudomonas aeruginosa, and amoxicillin (empirically started on admission) was replaced by meropenem. 2 weeks later, still in hospital and being treated with meropenem, he developed headache, neck pain, and a left abducens nerve palsy. Repeated chest radiography and MRI of the brain were normal. Cerebrospinal fl uid (CSF) analysis showed only a mild pleocytosis (leucocytes 17×106 per L). The clinical picture suggested a chronic (basal) meningitis, but blood and CSF cultures remained negative. The patient refused meningeal biopsy and further treatment, had progressive diffi culty in swallowing, and died 3 weeks later in hospital from pneumonia. Autopsy showed a focal purulent pre pontine lepto meningeal exudate (fi gure B). Micro scopically, multiple septated and branched hyphae were detected in this exudate and in the left middle and internal ear (fi gure C), combined with chronic-active necrotising infl am mation. The infl ammation extended into the skull base and cranial nerves. A mould cultured from the exudate was characterised as Pseudallescheria boydii by sequence-analysis of parts of the β-tubulin gene. P boydii can cause a wide variety of clinical diseases and is commonly found in soil, polluted water, and manure. P boydii infections of the central nervous system (CNS), meninges, and mastoid are very rare and generally occur in immunocompromised, near drowning, and trauma patients, but have also been reported in patients without one of these risk factors. There was no suspicion of immunocompromise in our patient, and post mortem HIV PCR analysis from lymph node and heart tissues were negative. Diagnosis of CNS involvement by P boydii is often delayed because of non-specifi c clinical presentation, diffi culty in obtaining and culturing appro priate specimens, and because of histological similarity of P boydii to other fungi, such as aspergillus. In our patient the fungus most likely gained access to the ear and CNS through tympanic membrane perforation. In patients with P boydii mastoiditis, surgical intervention, adequate anti-fungal therapy, and identi fi cation and control of underlying immunological conditions are essential. Voriconazole is suggested as the treatment of choice. Awareness of P boydii as a cause of chronic mastoiditis and meningitis may allow early diagnosis and treatment, thereby increasing the chance of resolution.

Congenital syphilis: β2-microglobulin in cerebrospinal fluid and diagnosis of neurosyphilis in an affected newborn

Meningoencephalitis in neonatal congenital syphilis (CS) is a difficult diagnosis because of the limitation of standard cerebrospinal fluid (CSF) tests. This limitation means that new markers in CSF tests are needed to establish whether meningitis is present in presumptive cases of CS. beta2-Microglobulin (beta2-m) is raised in CSF recovered from neonates with central nervous system (CNS) infections, but it does not correlate with cellular count or proteins in the CSF. We present a preterm newborn with symptomatic CS. First-day CSF showed 50 cells/mm3, protein of 220 mg/dL and a beta2-m concentration of 16.9 mg/dL (normal <2.25 mg/dL). Serial determinations of beta2-m showed a marked reduction (76%) after 10 days of appropriate treatment. At 30 days of life, beta2-m was already within the normal range (1.8 mg/dL). Cerebral ultrasonography showed ventricular dilatation, moderate periventricular echogenicity, subependimal hemorrhages, and linear hyperechoic areas in the thalamus and basal ganglia. We suggest that beta2-microglobulin is very useful in the diagnosis of CNS involvement and in monitoring the response to treatment. In addition, infants with CS may exhibit CNS imaging findings similar to those observed in other intrauterine CNS infections.

Cerebral Metastases Secondary to Ovarian Cancer: Still an Unusual Event

An incidence of cerebral metastases secondary to epithelial ovarian cancer as high as 11.6% has been reported in small series and related to the prolonged survival of ovarian cancer patients treated with platinum compounds (Hardy, J. R., and Harvey, V. J. Gynecol. Oncol. 33, 296-300, 1989). A review of the histories of 413 ovarian cancer patients, treated from 1981 to 1989 with platinum-based combination chemotherapy according to the protocols of the Gruppo Oncologico Nord Ovest (GONO) (North West Oncology Group), showed that only 9 patients (2.2%) developed clinical evidence of cerebral metastases. Six of 9 patients had FIGO Stage IIIc disease and 1 each with FIGO Stages Ic, IIc, and IV. All these patients had received cisplatin or carboplatin-based combination chemotherapy. Clinical response to initial cytotoxic therapy was as follows: complete response, 3 patients; partial response, 4 patients; stable disease, 1 patient; progressive disease, 1 patient. Cerebral metastases occurred at a median of 19 months (range 3-36) from diagnosis and median survival of patients with central nervous system (CNS) metastasis was 26 months (range 10-81) from diagnosis of primary disease and 8 months (range 1-45) from diagnosis of CNS involvement. The incidence of CNS metastases in our series is similar to that reported in the past and significantly lower than figures reported by the above mentioned paper. On the basis of our data we do not agree with Hardy and Harvey about the relationship possibly existing between prolonged survival and incidence of CNS metastases and, particularly, about the need for prophylactic cranial irradiation.

Central nervous system involvement in malignant melanoma.

One hundred consecutive patients with cerebral metastases from malignant melanoma were studied in relation to survival from the time of diagnosis of central nervous system (CNS) involvement, response to treatment, characteristics of their primary lesion, and the course of the disease from initial diagnosis to the development of intracranial tumor. After treatment, clinical and investigational evidence of objective regression of cerebral lesions was demonstrable in ten patients who survived with a median of 11.5 months from diagnosis of CNS involvement. In 11 additional patients, CNS disease remained clinically stable for a median period of 7 months. Median survival for the entire group of 100 patients was 2.5 months. However, eight patients (8%) survived longer than 1 year from the time of diagnosis of cerebral metastases, four of whom (4%) survived longer than 2 years; the longest survivor being disease-free and incomplete neurologic remission at more than 82 months. Patients with malignant melanoma metastatic to the brain should be informed of the therapeutic options available for their disease.

Beta 2-microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.