Cerebral toxoplasmosis and AIDS. Clinical, neuroradiological and immunological findings in 15 patients.

Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and its incidence ranges from 3% to 40% of such patients. This opportunistic infection is generally due to reactivation of chronic toxoplasmosis as a consequence of severe immune deficiency. We present the clinical, neuroradiological and immunological findings of 15 AIDS patients with cerebral toxoplasmosis. All patients had focal neurological signs. CT-scan (13 cases) and NMR (2 cases) showed single or multiple mass lesions and edema. Serum IgG anti-Toxoplasma antibodies were positive in 14 patients; CSF specific IgG were positive in 5 out of 7 studied patients, while serum and CSF specific IgM were negative in all subjects. The intrathecal synthesis of anti-Toxoplasma antibodies were high in all 7 patients. A presumptive diagnosis of cerebral toxoplasmosis is based on the focal cerebral signs and neuroradiological findings. It is more frequently confirmed by the improvement of the clinical and neuroradiological picture during the treatment with pyrimethamine-sulphadiazine or clindamycin.     

Cerebrospinal myelin basic protein in multiple sclerosis. Identification of two groups of patients with acute exacerbation

The myelin basic protein concentration in the cerebrospinal fluid (CSF) of 125 patients with multiple sclerosis was measured using a radioimmunoassay technique with a detection level of 200 pg/mL and was correlated with the clinical course of the disease. Myelin basic protein was detected in the CSF of some patients with an active progressive form of the disease and in the CSF obtained during exacerbations with the presence of signs or symptoms not previously experienced by the patient (26 of 29 cases were positive during the period of maximal symptoms). Myelin basic protein was not detected in any patient with an inactive or slowly progressive form of the disease, nor in any patient during exacerbations with only recurrence of old signs or symptoms. These results are consistent with the hypothesis that the two clinical forms of exacerbation defined above may be associated respectively with the absence or presence of an acute demyelination.     

Patients with Alzheimer's disease and dementia with Lewy bodies mistaken for Creutzfeldt-Jakob disease.

OBJECTIVES: To describe the clinical presentation of patients with Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) who were suspected of having Creutzfeldt-Jakob disease (CJD) and to investigate whether current clinical diagnostic criteria cover these atypical forms of AD and DLB. METHODS: Brains from necropsy were examined for the diagnosis of CJD at the German reference centre for spongiform encephalopathies. Symptoms and signs in patients with suspected CJD in whom necropsy showed AD (n=19) or DLB (n=12) were analysed. Their data were compared with a group of patients with CJD (n=25) to determine overlapping and discriminating clinical features. All patients were classified according to clinical diagnostic criteria for CJD, AD, and DLB. RESULTS: Demented patients were suspected of having CJD if disease was rapidly progressing and/or focal neurological signs appeared and/or an EEG showed sharp wave complexes. Myoclonus and limb rigidity were the most common neurological signs in all three dementias. DLB was not suspected in any patient, although patients with DLB showed parkinsonism (58%) and fluctuations (58%). Periodic sharp wave complexes (PSWCs) in EEG typical of CJD were found in five patients with AD and one patient with DLB. 14-3-3 Protein in CSF was detected in 20 patients with CJD, in two patients with AD, but not in any patient with DLB. Although most patients with DLB or AD met the clinical criteria for their respective diagnosis (74% and 90%), they also fulfilled criteria for CJD (42% and 58%). CONCLUSIONS: In patients with rapidly progressive dementia and focal neurological signs, CJD should be the first line diagnosis. Facing the triad dementia, myoclonus, and rigidity, AD should be considered if the disease course is longer and DLB is the differential diagnosis if parkinsonism or fluctuations are present. Findings on EEG or CSF typical of CJD do not exclude AD or DLB.     

影响正常压力性脑积水分流术的预后因素

目的 探讨影响正常压力脑积水行脑脊液分流手术预后的因素.方法 从27例正常压力脑积水病人临床症状、病程、腰穿放液和引流试验等因素分析手术效果.结果 术后随访3个月～3年,依照疗效判定标准,显效7例(25.9％);有效15例(55.6％);无效4例(14.8％).其中以步态不稳改善最明显,以痴呆、尿失禁为主要症状者疗效较差.腰穿测CSF平均压力≥140 mmH2O者优于压力＜140 mmH2O的患者;腰穿压力＜ 140 mmH2O,且24 h CSF总引流量＜250 ml、夜间12 h CSF引流量＜150 mL的患者疗效最差.结论 对正常压力性脑积水,根据临床表现及脑脊液动力学的变化可以预测NPH分流手术的有效性.     

DIAGNOSTIC SIGNIFICANCE OF CEREBROSPINAL-FLUID EXAMINATIONS IN MYELOPATHY

The diagnostic significance of CSF signs in myelopathy has been investigated. The CSF signs were compared with the other clinical data in 103 patients: 58 with myelopathy of known cause and 45 with that of undetermined cause. All the patients had been thoroughly examined, e.g. in most cases gas myelography was performed. The CSF examinations included cell analyses, determination of the protein concentration, electrophoresis and, generally, mastix reaction. The same technique of paper electrophoresis was employed in the entire material. The results were classified in accordance with characteristic patterns, corrected for serum electrophoretic distributions (Kjellin 1969). Forty % of the cases of myelopathia NUD were demonstrated at the clinical follow-up examinations to be either proved or probable MS, in good agreement with the initial CSF signs. About 20 % had slightly pronounced CSF signs similar to those in MS, but which hitherto had not been supported by a clinical diagnosis. About five % were meningo-myelitis or atypical MS. Thus, more than 60 % of myelopathia NUD cases may be MS with apparently a special clinical pattern: a relatively high age of onset and frequently a protracted, slow progression of the symptoms, with spinal localization of long duration. Systemic diseases were the cause of myelopathy in from five to seven %. In about five % of the myelopathia NUD cases there were “degenerative”, electrophoretic, CSF patterns. In about one-fourth unspecific (“barrier-damage”) signs were present or nothing noteworthy was found. Pronounced CSF signs, as seen in MS, were present in 44 % of the patients with myelopathia NUD, but only in 3 % of those with myelopathy with determined cause; one patient with B₁₂-myelopathy and the other with disc protrusion, possibly with concomitant MS. It should be pointed out that increased CSF-gamma-globulin concentrations should be given serious consideration in cases where disc protrusions are the supposed cause of myelopathy. If signs of obstructed spinal CSF flow are absent, the diagnosis MS has to be taken into consideration.     

Seven cases of huntington''s disease in childhood and levodopa induced improvement in the hypokinetic — Rigid form

Seven cases of the infantile form of Huntington's disease — six boys and one girl — were observed in the space of six years. Six children showed the hypokinetic-rigid form of the disease. Results of clinical, speech evaluations, laboratory tests, EEG and LPEG corresponded with data in literature. Initial signs and symptoms were mild sensorimotor and behavioural disturbances. In five patients, all affected by the hypokinetic-rigid form, CSF HVA and 5HIAA were determined. CSF HVA levels were found to be significantly lowered in three patients. One child showed significant decrease of CSF 5HIAA. Levodopa, orally administered to these five patients during 8 days to 6 weeks in dosages of 75 to 600 mg per day. induced in all a marked improvement of the hypokinesia and/or rigidity, speech and social behaviour. Two children developed slight choreatic movements and one child had to be withdrawn from the drug because of decrease of appetite.     

颅内静脉窦血栓形成的临床与影像学特点

目的探讨颅内静脉窦血栓形成(CVST)的临床与影像学特点。方法对17例CVST患者的临床资料进行回顾性分析。结果本组17例CVST患者的平均年龄为34.4岁,≤45岁的中青年患者12例(70.6%)。常见的临床症状:头痛15例(88.2%),癫痫发作5例(29.4%);体征:颈抵抗(+)8例(47.1%),视盘水肿4例(23.5%)。16例患者行腰穿CSF检查示压力增高15例,CSF细胞数和蛋白含量轻度增高分别为3例、4例。头颅CT检查显示CVST的直接征象3例(17.6%),间接征象10例(58.8%)。MRI检查显示CVST的表现15例(88.2%);MR静脉造影(MRV)检查有16例患者(94.1%)显示颅内静脉窦血流缺失或降低。经低分子肝素抗凝或合并肠溶阿司匹林、巴曲酶,以及脱水降颅压、抗感染等治疗后,基本痊愈+显著进步11例(64.7%),无变化4例(23.5%),死亡2例(11.8%)。结论 CVST大多为中青年发病,临床表现无特异性。头颅CT对CVST的诊断价值较低;而MRI和MRV诊断CVST的准确性高,能显示颅内静脉窦闭塞的表现。本病抗凝治疗的效果较好。     

Chronic mumps virus encephalitis. Mumps antibody levels in cerebrospinal fluid

To study the outcome of mumps virus encephalitis 47 patients were contacted 1-15 years after the acute encephalitis associated with mumps virus infection. Twenty-three patients experienced clinical sequelae such as difficulties in memory and learning, focal motor or sensory signs, and loss of hearing and visual acuity. Lumbar puncture was performed on 8 patients. Antibodies to mumps virus were detected in 6 cerebrospinal fluid (CSF) specimens using enzyme immunoassay and in 3 patients an abnormal serum/CSF antibody ratio was observed 11, 26 and 58 (controls greater than 85); 14.3, 1.4 and 6.1 years after the acute encephalitis, respectively. Antibodies to other microbes were either undetectable in the CSF or the serum/CSF ratios were normal. The clinical sequelae in about half of the patients and the signs of intrathecal mumps antibody production are suggestive of a chronic process in the central nervous system after encephalitis associated with mumps virus infection.     

Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children

We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis.     

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657+/-124.9 ng/ml) or remission (627+/-36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity.     

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.     

Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.     

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years’ duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2–117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1–19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia. Received: 20 February 1997 Received in revised form: 16 July 1997 Accepted: 1 August 1997     

Experimental allergic encephalomyelitis in mice: presence of myelin basic protein in cerebrospinal fluid

The concentration of myelin basic protein (MBP) in cerebrospinal fluid (CSF) correlates with the development of experimental allergic encephalomyelitis following intradermal injection with encephalitogen in adjuvant; MBP is absent in controls inoculated with adjuvants only. The presence of MBP is a sensitive indicator of disease inasmuch as CNS-inoculated mice with neurologic signs had an average of 0.29 ng/microliter of MBP in their CSF and controls, including normal or adjuvants only, had an average of 0.03 ng/microliter. The amount present per microliter of CSF, as well as the absolute amount, obtained from an individual mouse do not always reflect the severity of disease as indicated by clinical signs and the pathology observed in a sampling of the neuraxis. The presence of MBP does correlate with demyelination, although the extent of pathology observed by light microscopy in the mouse model is minimal, associated only with the inflammatory response, and does not extend beyond the zone of the perivascular cuff.     

Myelin basic protein in the cerebrospinal fluid of patients infected with HIV

Summary The major pathological abnormalities of HIV encephalopathy are infiltrates of macrophages, multinucleated giant cells, microglial nodules and demyelination. Elevated myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) provide a marker for central nervous system demyelination. The purpose of this study was to investigate the possible role of CSF MBP as a useful and early marker for HIV encephalopathy. The CSF of 40 consecutive patients with HIV infection of various clinical stages was investigated, including 13 patients with clinical signs of HIV encephalopathy. CSF MBP was elevated in 2 patients (5.0 and 5.3 ng/ml), both of whom had moderate to severe HIV encephalopathy. The course of the disease was rapid in both patients. In the remaining 38 patients, CSF MBP levels were marginally elevated (n=12) or normal (n=26). Our results suggest that CSF MBP is not a sensitive marker for the diagnosis and evaluation of HIV encephalopathy, but may be an indicator of prognosis for the course of the disease. There were only few findings of elevated CSF MBP levels in patients with HIV encephalopathy in the current study, and this may be because the disorder progressed slowly in most patients. It is possible that CSF MBP levels in HIV encephalopathy may only be elevated with acute clinical deterioration but are normal in slowly progressive forms of demyelination, as seen in multiple sclerosis.     

Encephaloradiculomyelitis associated to HHV-7 and CMV co-infection in immunocompetent host

An active co-infection with CMV and HHV-7 has been never described in immunocompetent patients. The authors describe a case of encephaloradiculomyelitis in an immunocompetent man. Polymerase chain reaction (PCR) performed on cerebrospinal fluid (CSF) showed positivity for DNA of Cytomegalovirus (CMV) and Herpes-virus type 7 (HHV-7), whereas the same test applied on peripheral blood mononuclear cells gave negative result. These results are highly supportive of an infection of the central and peripheral nervous systems, caused by CMV and HHV7. Such viral co-infection has only been described in immune-depressed patients with CMV disease, in which HHV-7 was supposed to act as a cofactor, enhancing clinical manifestations. The same mechanism is presumably responsible for the development of encephaloradiculomyelitis clinical signs in the present case. This is the second case in which DNA of HHV-7 has been found in the CSF of an adult immunocompetent patient. This novel observation suggests that the search for viral DNA in the CSF should be performed also in immunocompetent patients.     

Lymphocyte subpopulations in the blood and cerebrospinal fluid of multiple sclerosis patients in active disease

Lymphocyte subpopulations (total T cells, active T cells and B cells) were simultaneously analyzed in peripheral blood and CSF of MS patients. All patients were in active disease, 3 to 4 weeks after first signs of disease activation appeared. Per cent levels and absolute numbers of examined lymphocyte subpopulations in the blood of MS patients were significantly lower than in healthy controls. In MS, the level of active T lymphocytes was lower in CSF than in peripheral blood. The results support our earlier observations relating to the role of active T lymphocytes in the clinical course of disease.     

Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA

OBJECTIVE: 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). METHODS: The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS (n = 49), CIS (n = 14) and OND (n = 53). RESULTS: A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. CONCLUSION: A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful.     

Central nervous system tuberculosis in children: 1. Clinical and laboratorial presentation

Tuberculosis still occupies a remarkable place as a worldwide health problem, chiefly in emerging countries, like Brazil. The central nervous system (CNS) involvement by Mycobacterium tuberculosis is one of the most feared features of disease, because of its high morbidity and mortality. This study aimed to describe some epidemiological, clinical and laboratorial aspects of 52 children in a tertiary pediatric hospital with CNS tuberculosis. At diagnosis, the majority of patients showed low age, compromised nutritional status, previous contact with bacillary individuals, delayed or absent immunization, advanced neurological signs and compatible abnormalities in cerebrospinal fluid (CSF) analysis and in radiological findings. The etiologic agent was identified by staining methods or CSF and other fluids culturing in 40% of patients. In most cases, despite of suggestive clinical, epidemiological and laboratorial picture and feasibility of patients access to health care centres, therapy was started late.