Joäo Baptista dos Reis Filho

Can thalidomide be effective to treat plasma cell leptomeningeal infiltration

To the Editor: Dear Sir, In May 2000, a previously healthy, 52-yr-old woman was diagnosed with Salmon-Durie stage IIIA, IgG j multiple myeloma (MM). She was initially treated with six cycles of intravenous (i.v.) vincristine 0.4 mg days 1–4; i.v. doxorubicin 9 mg/m days + 198 1–4; P. O dexamethasone days 1–4, 9–12, 17–20 (VAD) every 4 weeks), the last interrupted because of Staphylococcus aureus endocarditis. At this time, during the infection treatment, she developed radicular symptoms associated with a paravertebral mass identified on computed tomography scan. The biopsy ruled out an abscess and showed a plasmacytoma. The patient underwent lumbar spinal irradiation (4000 cGy) followed by six cycles of i.v. cyclophosphamide 750 mg/m day 1: i.v. doxorubicin 50 mg/m day 1; vincristine 1, 4 mg/m day 1; P. O prednisone 60 mg/m days 1–5 (CHOP), achieving complete clinical response. In December 2000, few days before the harvest of peripheral stem-cell for autologous transplantation, she was confused and hemiparetic on physical examination. A cranial magnetic resonance imaging showed a left parietal mass. Cerebrospinal fluid (CSF) showed 250 cells/ mm, with 100% of plasma cells (Fig. 1). This finding was confirmed by flow cytometry analysis of CSF (CD45–, CD38+, j+). There were no other signs of systemic activity of the disease (no serum or urinary M protein, <5% plasma cells in the bone marrow). She was treated on oral dexamethasone (40 mg on days 1–4, 9–12, 17–20 with interval doses of 16 mg/d) and three doses of weekly intrathecal chemotherapy (methotrexate 12 mg and dexamethasone 2 mg). Despite a brief period of symptomatic relief, there was no CSF cleansing (CSF on 11/30/2001: 640 cells/mm, 100% plasma cell; CSF on 02/14/2002: 80 cells/ mm, 100% plasma cells) and the neurologic symptoms ended up progressing (see Table 1). The patient was then treated with thalidomide (Thal) 800 mg/d for 30 d with simultaneous cranial radiation, achieving total dose of 1000 cGy. Radiotherapy was interrupted because the patient’s focal deficits worsened and her mental status deteriorated, resulting in progression to death 3 months after detection of the central nervous system involvement. In this study, we describe a very unusual complication in MM with 53 cases previously related in the literature. Meningeal myelomatosis, defined as meningeal involvement by plasma cells in the CSF, although might be a presenting feature, has usually been described in the setting of pre-existing MM (1). It tends to occur in stage III disease and is associated with plasma cell leukemia in 20% of patients. Few patients were reported to relapse with meningeal compromising and limited disease outside the central nervous system (CNS) (2). We questioned the role of the paraspinal plasmacytoma as the seeding source of plasma cells into CSF (3). As the meningeal myelomatosis represents a dismal event, with 1– 2 months median survival despite aggressive local treatment, associated or not with systemic therapy (1), we tried to treat this patient with Thal and radiotherapy following intrathecal chemotherapy and high dose glucocorticoid. We were expecting a better outcome than that previously reported, assuming the usefulness of Thal in relapsed/ refractory MM patients (4), the high angiogenesis Fig. 1. Cytospin of CSF sample showing 100% of dysplasic plasmocytes, confirming the diagnosis of leptomenigeal infiltration in our patient, ·1000. Eur J Haematol 2003: 70: 198–199 Printed in UK. All rights reserved Copyright Blackwell Munksgaard 2003

Criptococose do sistema nervoso central: experiência atual do Serviço de Neurologia da Escola Paulista de Medicina

Os autores ressaltam a importância da pesquisa de criptococo em todos os pacientes com quadro clinico de meningite, meningo-encefalite ou hipertensao intracraniana nao identificados, associados a um quadro inflamatorio no liquido cefalorraqueano. Procedendo sistematicamente esta pesquisa pelo exame a fresco, pelo metodo da tinta china, no liquido cefalorraqueano, os autores fizeram o diagnostico em vida de 35 pacientes, durante o periodo 1953-1972. Alem destes, foi observado um outro caso com a forma granulomatosa pura, o que perfaz 36 observacoes. A distribuicao cronologica destes casos no correr destes 20 anos de observacao foi relativamente uniforme, nao se justificando a hipotese de um aumento de sua incidencia. As idades dos pacientes estavam compreendidas entre 11 e 59 anos, a maioria entre 30 e 50; apenas 8 pertenciam ao sexo feminino. Dos primeiros 12 pacientes da epoca em que nao se dispunha de meios terapeuticos, apenas um sobreviveu para se beneficiar ulteriormente. Com o advento da Anfotericina B tornou-se possivel o tratamento de 24 destes pacientes que apresentavam a forma de meningite ou meningo-encefalite. Foi obtida a cura, com normalizacao clinica e do liquido cefalorraqueano, de 11 pacientes; 8 pacientes nao completaram o tratamento, tendo se retirado do Hospital depois das primeiras melhorias, ignorando-se, por isso, a evolucao final; 5 pacientes faleceram. A 5-fluorocitosina foi experimentada em um dos ultimos pacientes desta serie, em asso- ciacao com a Anfotericina B, de modo que os autores nao tem experiencia sobre o valor real deste novo medicamento.The authors emphasize the importance of the search of cryptococcus in every patient with signs and symptoms of meningitis, meningo-encephalitis or intracranial hypertension and with inflammatory changes in the spinal fluid. With this idea in mind, they have performed the India ink test in the spinal fluid of every patient in the 1953-1972 period and were able to make the diagnosis of cryptococcal meningitis in 35 cases. Furthermore, there was another case with granuloma localized in the spinal cord. These 36 cases were distributed more or less regularly during these 20 years of observation, suggesting that there was no increase in the incidence. The age of the patients ranged between 11 and 59 years, mostly between 30 and 50 years. Only 8 of them were female patients. Of the 12 patients seen at the time when there was no real treatment, only one outlived to get the benefit of modern therapy. When amphotericin B was available, 24 patients with cryptococcal meningitis were treated and 11 had a successful outcome with spinal fluid normalization; 8 patients have not finished the complete series of injections and left hospital after the first clinical improvements; finally, 5 patients have failed to improve and had a fatal outcome. The authors have no experience with 5-fluorocytosine, because they used it only in one case and in association with amphotericin B.

Líquido cefalorraquidiano no diagnóstico da esquistossomose raquimedular

Cerebrospinal fluid (CSF) changes in spinal shistosomiasis have been described. Its characteristic features are mild to moderate pleocytosis, presence of eosinophils, slight to moderate protein increase, elevated gamma globulin concentration and a positive immune assay. Nevertheless, these abnormalities are not always present together and therefore difficulties may arise in the assessment of the diagnosis. The purpose of this paper is to evaluate the importance of each CSF alteration concerning the diagnosis in 22 cases of spinal shistosomiasis. According to the results, only 20% of the cases had all the five feature that are considered to be characteristic of spinal shistomiasis. Abnormal cell count was present in 86%, protein increase in 77.3%, immunoglobulin G increase in 60,8%, eosinophils were present in 36.8% and indirect fluorescent antibody test was positive in 68.2%. In three cases all CSF parameters studied were within the normal limits. As the most specific test among those described was the indirect fluorescent antibody test, it should be regarded for the diagnosis.

Os basófilos do líquido cefalorraqueano

The references to the basophil type of granulocyte of the abnormal cerebrospinal fluid are strictly limited and deficient. Some authors describe them as tissue basophils (mast cells) stating that there are no basophil granulocytes in the spinal fluid. The purpose of this paper is to contribut to the study of this subject. The material of the study consisted of the clinical records of 300 neurologic patients whose spinal fluid cytologic examinations revealed the basophils. The results of these studies showed that the basophils of the cerebrospinal fluid and the blood basophils are morphologically identical. However, the lack of correlation between the number of basophils in the blood and in the spinal fluid suggests that the basophil of the spinal fluid comes from the leptomeninges and in a sense it is a tissue basophil. In the group of patients with inflammatory diseases of the nervous system (Group 1), mostly cases of lymphocytic meningitis, meningo-encepha- litis, and meningomyelitis, the basophils ranged between 0.1 and 18 per cent. In the cases of purulent and tuberculous meningitis the basophils were observed in a lesser number (0.1 to 5 per cent). In the group of patients with changes in the cerebrospinal fluid due to subarachnoid hemorrhage, brain cysticercosis and air injected into the subarachnoidal space (Group 2), the basophils ranged between 0.1 and 11 per cent. In several patients plasma cells and eosinophils were frequently observed in association with the basophil leucocytes. There was a good correlation between basofils and eosinophils in the group of patients with problable immune-allergic reactions (Group 2). Basophils disappear rapidly from the spinal fluid after the onset of the disease. Usually basophils are seen in cases with spinal fluid pleocytosis, but it is not uncommon to observe them in cases with normal cell count. We know nothing about the meaning of the spinal fluid basophil in relation to central nervous system diseases and this is a field open to clinical and experimental investigations. It would be tempting to suggest that basophils do appear in the spinal fluid as part of the cytologic changes which point out to an immune-allergic reaction in its acute phase.

Sindrome de Vogt-Koyanagi-Harada: relato de um caso

The Vogt-Kayanagi-Harada sśyndrome in two negro female patients with 37 and 40 year-old, respectively, are reported. The clinic, epidemiologic, heredo-familial and immunologic aspects are discussed.A case of Vogt-Koyanagi-Harada syndrome which had an ocular onset unilateral in the beginning and bilateral afterwards is reported. One month after the disease had apeared a psychiatric disturbance was detected characterized by mania and loss of the critical sense. The alterations detected in the eletroencephalograms and cerebrospinal fluid are discussed. After a three and a half years follow up, despite the corticotherapy the patient had a poor evolution on the ophtalmological aspect but the psychiatric recovery was total.

Contagem diferencial das células do líquido cefalorraquiano pelo método da sedimentação gravitacional facilitada: conceito de normalidade

Cisternal or lumbar cerebrospinal fluid (CSF) specimens of 59 healthy persons were examined for differential cell count with a new improved sedimentation chamber, similar to that one of Sayk. The purpose of this study was to compare our results to those already described in the literature. Techinical care was taken in order to increase the accuracy of this investigation and it consisted mainly of counting all the existing cells in the preparation, and not only 100 cells or a lesser number, recorded in percentage. The results of this survey have shown that the normal mean values for the CSF cytomorphology are 58.8 per cent lymphocitic cells, 41.0 per cent monocytoid cells, and 0.2 per cent neutrophilic granulocytes. These figures are in good agreement with those already reported by numerous authors, when we consider the lymphocytic and monocytoid cells, but they revealed a fact seldom seen reported: the possibility of a few neutrophilic granulocytes as a constituent of the normal CSF cytomorphology.: Cisternal or lumbar cerebrospinal fluid (CSF) specimens of 59 healthy persons were examined for differential cell count with a new improved sedimentation chamber, similar to that one of Sayk. The purpose of this study was to compare our results to those already described in the literature. Technical care was taken in order to increase the accuracy of this investigation and it consisted mainly of counting all the existing cells in the preparation, and not only 100 cells or a lesser number, recorded in percentage. The results of this survey have shown that the normal mean values for the CSF cytomorphology are 58.8 per cent lymphocitic cells, 41.0 per cent monocytoid cells, and 0.2 per cent neutrophilic granulocytes. These figures are in good agreement with those already reported by numerous authors, when we consider the lymphocytic and monocytoid cells, but they revealed a fact seldom seen reported: the possibility of a few neutrophilic granulocytes as a constituent of the normal CSF cytomorphology.

Eosinofilorraquia em tumor maligno: apresentação de caso

It is presented a case of a patient with a cerebral malignant astrocytoma in which the spinal fluid cytomorphology showed numerous eosinophilic granulocytes.

Alterações do líquido céfalorraqueano e perturbações do sistema nervoso central em distúrbios do controle hidrogênio-iônico: estudo da relação cloretos/CO2 total

O LCR constitui um meio muito pobre em proteinas e o seu poder tampao depende fundamentalmente da relacao pCO2/HCO3-. O LCR e, por assim dizer, uma solucao salina bicarbonatada a qual se juntam pequenas quantidades de outros componentes ionicos e moleculares. Admite-se que a barreira hemato-encefalica protege o sistema nervoso central contra as variacoes subitas do equilibrio hidrogenio-ionico. Ela apresenta uma lenta permeabilidade as variacoes de concentracoes dos iontes HCO3-, Cl-, H+, Na+, de que resulta protecao do pH do LCR, e facil permeabilidade ao gas CO2 de sorte a favorecer rapidos ajustes com o sangue. Estes fatos explicam porque, por vezes, podem ser observadas variacoes divergentes do pH de um lado e de outro da barreira. Por motivo de sua importante funcao fisiologica na regulacao da respiracao, o LCR esta muito bem protegido em relacao a estabilidade de seu pH. Alem disto o pH do LCR indica mais fielmente as modificacoes acido-basicas do tecido cerebral que o pH do sangue. Os disturbios graves do controle hidrogenio-ionico determinam perturbacoes da funcao cerebral com manifestacoes neurologicas e psiquicas. Por estes motivos as determinacoes do pH, pCO2, e CO2 total do LCR tem uma grande importância para a interpretacao dos problemas fisiopatologicos que ocorrem no sistema nervoso central, para o consequente diagnostico e para a correta indicacao terapeutica. Pouco se sabe sobre as perturbacoes da funcao do sistema nervoso central em pacientes com acidose metabolica; ja se tem descrito disturbios neurologicos e mentais em pacientes com alcalose respiratoria e alcalose metabolica; entretanto, e em relacao a acidose respiratoria que a literatura e mais extensa. Na acidose respiratoria decorrente da insuficiencia ventilatoria pulmonar grave pode-se observar uma sindrome de hipertensao endocraniana devida a acao vasodilatadora do CO2 e estes pacientes sao por vezes encaminhados aos servicos neurologicos com a suspeita de tumor encefalico. O proposito do presente trabalho foi o de determinar a relacao cloretos/ CO2 total no LCR normal e no LCR de pacientes neurologicos com disturbios mais comuns do controle hidrogenio-ionico, para se poder avaliar o seu valor pratico no exame de rotina. O material deste estudo e constituido por 58 observacoes, sendo 37 de pessoas normais e 21 de pacientes com disturbios graves do controle hidrogenio-ionico, dos quais 11 apresentavam acidose respiratoria e 10 acidose metabolica decorrente de coma diabetico. Em condicoes normais, a relacao cloretos/CO2 total no LCR esta compreendida entre os valores de 4.8 a 5.8. Nos disturbios do controle hidrogenio-ionico, particularmente naqueles casos cronicos e graves, verificam-se alteracoes das taxas de cloretos e de CO2 total, cujas concentracoes variam de modo compensatorio, umas em sentido oposto as outras, nestes ajustamentos acido-basicos. Na acidose respiratoria o LCR apresenta acentuada diminuicao da taxa de cloretos com aumento compensatorio da concentracao do CO2 total. Nestes casos a relacao variou de 2.0 a 4.7. Na acidose metabolica, como exemplo aquela que ocorre em pacientes em coma diabetico, observa-se diminuicao acentuada da concentracao do CO2 total e aumento da taxa de cloretos. Nestes casos, os valores da relacao cloretos/CO2 total estavam compreendidos entre 6.5 a 22.

Variações da taxa de açúcar no líquido cefalorraqueano em casos de derrame de sangue no espaço sub-aracnóide com especial referência à hipoglicorraquia

The chronologic changes of the glucose content in the hemorrahgic cerebrospinal fluid (CSF) in 515 cases have been studied, from the first to the tenth day. A traumatic origin was noticed in 156 cases and 359 were from miscellaneous origin. The diabetes mellitus and the meningitis cases were excluded from the study. The highest glucose content was 245 mg/100 ml and the lowest one was 12 mg/100 ml. The main purpose was to analyse the cases of low glucose levels in the CSF to find out if this would occur in a certain phase of the hemorrhagic event. The conclusions were the following: 1. there was a tendency for high glucose levels in the first few days of the hemorrhagic episode and progressive normalization on the following days: 2. the probability of occuring low glucose levels between the 6th and 8th day of the hemorrhagic event was not confirmed; 3. there were 32 cases with hypoglycorrhachia (6,2% of the total); 4. the intensive xanthochromia that was noticed in all cases with hypoglycorrhachia perhaps would be in behalf of the enzymatic theory and/or the theory of blood-brain barrier block in order to explain these findings.