Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study

BACKGROUND: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. METHODS: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. FINDINGS: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82%) and hydrocephalus (77%) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0.217). Tuberculomas developed in 74% of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27%vs 58%, p=0.130). INTERPRETATION: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.     

新型隐球菌性脑膜炎与结核性脑膜炎的临床特点比较

目的对比和分析综合性医院新型隐球菌性脑膜炎(CNM)与结核性脑膜炎(TBM)的临床特点。方法分析62例CNM及219例TBM患者的一般资料、临床症状、脑脊液细胞学(CSFC)、头颅影像学的特点。结果两种脑膜炎均呈亚急性或慢性起病相对于TBM,CNM延误诊断时间更长、临床症状中癫痫出现比率(24.2%)、头颅影像学中脑膜强化出现比率(17.7%)较高,腰穿脑脊液(CSF)压力(268.7±67.6mmH_2O)、CSF单核细胞占比(21.0±17.5%)高,CSF白细胞计数(84.8±88.1×10~6/L)、CSF糖(1.9±1.4mmol·L~(-1))较低。结论两种脑膜炎临床表现不典型,两者之间不易鉴别,容易误诊漏诊。临床上需综合判断,CSF瑞氏吉姆萨染色和改良抗酸染色有助于两者病原学确诊。     

Cerebrospinal fluid enolase in stroke.

This study relates the level of alpha and gamma enolase in cerebrospinal fluid sampled within 4 days of a stroke to the volume of the cerebral infarct measured on the CT image and to the clinical outcome of the patient. Twenty-eight patients were studied, two with transient ischaemic attacks and 26 with completed stroke due to infarction. The cerebrospinal fluid enolase was raised in the two patients with transient ischaemic attacks and 23 with completed stroke. There was a positive correlation between the volume of the infarct and the level of cerebrospinal fluid alpha and gamma enolase. A high cerebrospinal fluid enolase was always associated with a poor prognosis.     

Triptans reduce the inflammatory response in bacterial meningitis.

Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.     

Quasi-normal cerebrospinal fluid in patients with acquired immunodeficiency syndrome and cryptococcal meningitis

We report eight patients with cryptococcal meningitis and a cerebrospinal fluid characterized by few or no white blood cells and chemistries that may be near normal. In four of these patients, only testing for cryptococcal antigen allowed the initial diagnosis. Seven of the patients had a certain diagnosis of AIDS. Six have died. Autopsies performed in two cases indicated a poor meningeal inflammatory response. Contrary to the findings in most immunodeficient patients, in AIDS cryptococcal meningitis may present with few cellular or biochemical abnormalities in the cerebrospinal fluid. In AIDS patients presenting with headache and fever or change in mental status, examination of the cerebrospinal fluid should not be limited to routine studies.     

原发中枢神经系统自然杀伤/T细胞脑膜淋巴瘤一例临床分析

目的 探讨原发中枢神经系统自然杀伤/T(NK/T)细胞脑膜淋巴瘤的临床特点和诊断方法.方法 报道1例原发中枢神经系统NK/T细胞脑膜淋巴瘤患者,并结合文献总结其临床特征.结果 患者青年男性,急性起病,表现为视物成双、头痛、呕吐,口角歪斜,短期内出现全身疼痛、四肢无力,腰穿白细胞和蛋白显著升高,脑脊液细胞学曙红亚甲基蓝Ⅱ和迈-格-姬染色可见大量异型淋巴细胞,核异型性明显,可见核分裂相;免疫细胞化学染色可见多数淋巴样细胞Ki-67阳性,提示为增殖活跃的淋巴瘤.脑脊液流式细胞学:97.98%的细胞表达细胞膜型CD3、CD7、CD56、CD2和CD5,部分表达CDs,免疫分型为恶性NK/T细胞;头颅MRI+强化提示双侧三叉神经增粗,软脑膜强化,增粗的三叉神经轻度强化;骨髓检查未见异常,胸腹CT及强化未见异常.依据患者的病史、体格检查、临床检测和疾病经过,诊断为原发中枢神经系统NK/T细胞脑膜淋巴瘤.结论 原发中枢神经系统NK/T细胞脑膜淋巴瘤是罕见的中枢神经系统淋巴瘤,具有特殊的免疫分型,临床表现为恶性进展的高颅压、脑神经和脊神经受累,脑脊液细胞学和流式细胞分型对确定诊断起关键作用,放化疗效果欠佳,预后差.

Abstract：

Objective To explore the clinical features and diagnostic method of primary natural killer( NK)/T cell meningeal lymphoma. Methods An unusual case of a 19-year-old male with primary NK/T cell meningeal lymphoma was reported. His clinical presentation and laboratory findings were discussed. The related literatures have been reviewed. Results The patient presented with diplopia,headache, vomiting and facial drooping at the onset, followed by progressive pain and weakness of the four limbs. Cerebrospinal fluid showed significant increase in pressure, leukocytes number, levels of protein,normal glucose and adenosine deaminase, negative tuberculosis antibody and sterile staining. In cerebrospinal fluid cytological analysis, May-Grunwald-Gimsa staining showed large number of atypical lymphocytes with irregular nucleus and nuclear fission, Ki-67 immunostaining showed extensive proliferative activity of the lymphoid cells. Flow cytometric immunophenotypic analysis of cerebrospinal fluid indicated 97. 98 percent of cells expressed surface CD3, CD7, CD56, CD2, CD5, and partially expressed CD8. This was a rare immunophenotype for NK/T-cell. Cranial MRI with gadolinium showed thickening of the trigeminal nerve with slight enhancement and diffuse leptomeningeal enhancement. CT of the chest and abdomen and bone marrow biopsies were negative. He was diagnosed as primary NK/T cell meningeal lymphoma based on the clinical features and related examination. Conclusions Primary NK/T cell meningeal lymphoma is a rare type of primary central nervous lymphomas which has special immunophenotype. The clinical features include progressive raised intra-cranial pressure, multiple cranial and spinal nerve involvements. Cerebrospinal fluid cytological analysis and flow cytometric immunophenotypic analysis are key work-up for diagnosis. It has poor response to chemotherapy and radiotherapy.     

脑梗死患者血液和脑脊液NSE质量浓度测定及其临床意义的相关性研究

目的　观察急性期和恢复期脑梗死患者血液和脑脊液的神经元特异性烯醇化酶 (neuron-specific enolase,NSE)质量浓度变化 ,探讨其与神经功能缺损程度、脑梗死体积、颅内压以及患者年龄等方面的相关性。方法　该实验采用酶联免疫吸附法 (enzyme-linked immunosorbent assay,ELISA) ,检测观察组 (4 6例 )、对照组 (2 5例 )血液及脑脊液 NSE质量浓度 ,并应用 SPSS1 0 .0统计软件包进行统计学分析。结果　急性脑梗死 (acute cere-bralinfarction,ACI)患者血液和脑脊液 NSE质量浓度显著高于恢复期患者和对照组 (P <0 .0 1 ) ;ACI患者脑脊液 NSE质量浓度显著高于血液 (P <0 .0 1 ) ;血液和脑脊液 NSE质量浓度与梗死体积均呈显著正相关 (P <0 .0 1 ) ,与出院时神经功能缺损程度呈显著正相关 (P <0 .0 1 )。结论　脑脊液或血清中的 NSE质量浓度是脑组织破坏后较合适的生化标记物 ,有助于判断脑梗死患者梗死范围、监测病情变化及疗效观察。     

Primary leptomeningeal melanocytosis presenting as chronic meningitis

We report a patient with primary leptomeningeal melanocytosis presenting as chronic meningitis. A previously healthy 27-year-old man presented with 2 months of severe headaches and photophobia. A lumbar puncture was notable for a highly elevated cerebrospinal fluid (CSF) protein level without pleocytosis. Imaging at the time of admission suggested only meningitis without the presence of parenchymal lesions. On the basis of the CSF findings, early meningeal biopsy was performed, leading to the diagnosis of a meningeal melanocytic neoplasm. Early meningeal biopsy should be considered in patients with meningitis when the CSF profile suggests the possibility of a central nervous system neoplasm.     

Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge

We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.     

Transient ischemic attacks with and without a relevant infarct on computed tomographic scans cannot be distinguished clinically. Dutch Transient Ischemic Attack Study Group

We prospectively studied clinical and computed tomographic (CT) scan findings in 79 patients with a transient ischemic attack (TIA) and a relevant cerebral infarction on CT, also known as cerebral infarction with transient signs (CITS). We compared the results with those of 527 concurrent patients with TIA and without cerebral infarction and also with 646 patients with persistent neurological symptoms and a relevant infarct on CT. All patients were participating in a multicenter trial. In both groups, most infarcts were of the lacunar type. Compared with TIAs without cerebral infarction, patients with CITS slightly more often had a history of hypertension (52% vs 33%), the attacks lasted longer (greater than 1 hour, 52% vs 34%) and disappeared more slowly (over the course of hours, 39% vs 24%), and the symptoms more frequently involved speech (61% vs 41%). Despite these small differences, the reverse--the prediction of evidence on CT of infarction on the basis of the nature or time course of symptoms--proved impossible, since in each category the majority of patients had a normal CT scan. In comparison with patients with stroke and visible infarction, patients with CITS slightly more often had abnormal speech (61% vs 45%) and had a larger number of attacks (multiple attacks, 46% vs 18%). In conclusion, we found only minor clinical differences between patients with TIA with or without a relevant infarct on CT and equally small differences between patients with CITS and patients with stroke and cerebral infarction. These clinical similarities do not exclude a difference in prognosis.     

貌似大脑半球病变的脑干梗死临床和影像分析

目的　分析貌似大脑半球病变的脑干梗死的临床和影像学特点及临床定位错误的原因。方法　连续1年观察发病 6h内收治的首发脑梗死 118例 ,先行OCSP(theOxfordshirecommunitystrokeproject)分型、NIHSS评分 (thenationalinstitutesofhealthstrokescale)和超早期头颅CT平扫 ,再结合 72h内的头颅MR筛出貌似大脑半球病变的脑干梗死。结果　 118例中首诊分型 5 0例为腔隙梗死 ,其中 4 4例行MR复查并证实貌似大脑半球病变的脑干梗死 12例。头颅CT均未检出脑干病灶 ,MR准确检出了脑干责任灶。病灶多在脑桥的三叉神经根平面、脑桥旁正中动脉的血供分布区。 11例病灶小于 2 0mm ,呈纵向条状、片状。结论　早期行MR有助于明确诊断貌似大脑半球病变的脑干梗死。对有糖尿病病史、起病有头晕、临床呈单纯运动性轻偏瘫或单纯性偏瘫的LACI,要注意其病灶有可能在脑干。     

结核性脑膜炎合并脑结核瘤的临床特点

目的探讨结核性脑摸炎(TBM)合并脑结核瘤的临床特点,以提高对本病的认识和诊治水平。方法对我院2001年1月-2009年12月收治的TBM合并脑结核瘤患者26例的临床资料进行分析,探讨本病的临床特点。结果在TBM合并脑结核瘤时,出现各种脑局灶性损害体征。脑脊液多数呈TBM典型改变。11例在CT及MRI上呈现"靶征",CT发现结核瘤数2～14个,平均6.5±4.2个。MRI发现结核瘤数为2～17个,平均7.4±4.4个。临床治愈出院19例,好转4例,死亡3例。结论 TBM合并脑结核瘤的患者,临床表现复杂,如果出现局灶性脑损害体征,应考虑本病的可能。脑脊液检查不能提示脑结核瘤的存在与否,CT和MRI能显示脑结核瘤的部位、大小及数目等。尽早规范的抗结核综合性治疗,多数病人恢复良好。     

Clinicoradiological features of tuberculous meningitis in patients over 50 years of age

Background and aim

Tuberculous meningitis (TBM) is a debilitating form of CNS tuberculosis with a high morbidity and mortality in spite of treatment. The diagnosis is based on clinical, radiological and laboratory features. The classical CT features of basal exudates, hydrocephalus, infarcts and granulomas have been mostly reported in younger individuals. Our aim was to study imaging features of TB meningitis in adults over the age of 50 years.

Materials and methods

Clinical, imaging and laboratory features of 53 adult patients over the age of 50 years (sixth to eighth decades) were studied retrospectively. Diagnosis of TBM was based on clinical and laboratory features.

Results

Imaging features were the conspicuous absence of typical features of TBM (ie, basal meningeal enhancement, hydrocephalus, infarcts/granulomas were seen in only a minority of patients).

Conclusions

CT features of TBM in elderly patients were few, atypical and non‐contributory for diagnosis, probably because of age related immune senescence. Strong clinical suspicion and correlation with laboratory findings is necessary for early diagnosis.The elderly population is increasing all over the world, including India, because of increased life expectancy. The incidence of tuberculosis has been estimated to be higher in elderly subjects than in younger populations.¹ Non‐specific clinical symptoms may be masked by illnesses prevalent in old age, such as diabetes mellitus, vascular diseases and malignancies. CT has been used in the evaluation of tuberculous meningitis (TBM) to identify complications and for prognosis. CT features include basal meningeal enhancement, hydrocephalus, infarctions and focal granulomas.² We report a retrospective study of clinical and radiological features of TBM in patients over the age of 50 years (sixth to eighth decades).     

Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging

OBJECTIVE: To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke. METHODS: The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed. RESULTS: Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01). CONCLUSIONS: Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies.     

自发性低颅内压综合征七例报告

目的研究自发性低颅内压综合征（SIH）的临床、脑脊液（CSF）和影像学的改变。方法对1年8个月时间收治的7例SIH患者观察其临床表现、CSF压力、生化指标及头颅CT和MRI增强扫描。结果当患者起立时即出现头痛、呕吐及颈强直,卧位时症状消失。CSF压力均低于7cmH2O。其中5例呈血性CSF,蛋白增高似蛛网膜下腔出血（SAH）。CT示脑室缩小。增强MRI示硬脑膜强化、硬脑膜下积液、桥脑扁平、桥池变窄及小脑扁桃体下疝的特征性改变。当临床症状好转时,其CSF压力和生化指标恢复正常。结论了解SIH的临床、CSF和MRI表现至关重要,因其极易与SAH相混淆。     

The electroencephalogram and acute ischemic stroke. Distinguishing cortical from lacunar infarction

One hundred consecutive cases of clinically diagnosed, acute forebrain infarction were studied using computerized tomography (CT) and electroencephalography (EEG). Computed tomography confirmed brain infarction in 91 patients and was normal in the remaining nine. Each EEG was read independently by two experienced electroencephalographers without knowledge of CT or clinical details and their findings were compared with those of CT. Lateralized theta and/or delta activity predicted ipsilateral cortical infarction with a sensitivity of 76% and specificity of 82%. In contrast, cerebral hemisphere lacunae produced similar EEG abnormalities in only a few cases (9%). Electroencephalography is particularly useful following stroke if the initial CT excludes hemorrhage but does not detect infarction. In conjunction with clinical details, the EEG can then be used to indicate the likelihood of cortical involvement and thus suggest the likely pathophysiologic mechanism of infarction.     

Cyanotic congenital heart disease with suspected stroke. Should all patients receive antibiotics?

Two patients with cyanotic congenital heart disease (CHD) and erythremia were seen for abrupt onset of focal neurologic deficits and/or seizure without signs of infection or increased intracranial pressure. Clinical features and initial computed tomography (CT) in both cases suggested stroke. Subsequent CT scans demonstrated cerebral abscess, proved at operation. Review of records of patients with CHD at the University of Rochester (NY) Medical Center from 1965 to 1981 disclosed 12 cases with brain abscess but only two cases with aseptic cerebral infarction. All but one patient with abscess were cyanotic. One third of patients with abscess had a clinical picture suggesting stroke. Clinical or radiologic features of half the cases indicated that cerebral infarction may have led to abscess formation. Diagnosis of brain abscess and immediate antibiotic therapy should be strongly considered in patients with cyanotic CHD who suffer a suspected cerebral infarction.     

Cerebral infarction in bacterial meningitis: predictive factors and outcome

In this study, we analysed the frequency, morphological patterns and clinical characteristics of cerebral ischaemia in bacterial meningitis. We sought to determine predictors for the development of vasculopathy and ischaemic infarction in patients with bacterial meningitis. Consecutive adult patients admitted between March 1998 and February 2009 to a neurological intensive care unit at a university hospital in Germany with the diagnosis of bacterial meningitis were included in the study. Standard criteria were used to define bacterial meningitis. From 68 patients with bacterial meningitis, six patients suffered from cerebral ischaemia (8.8%). In our cohort, reduced level of consciousness on admission (p = 0.01) and lower white blood cell (WBC) count in cerebrospinal fluid (CSF) (p = 0.012) were associated with development of ischaemic cerebrovascular complications. The short-term outcome of all patients was poor (median modified Rankin scale 4.5). In patients presenting with reduced level of consciousness on admission and/or low WBC count in CSF early cerebral imaging including MR angiography or CT angiography are warranted to detect impending cerebrovascular complications.     

Hydrocephalus and tuberculous meningitis in children

Hydrocephalus constitutes one of the most common complications of tuberculous meningitis. Twenty-six cases of tuberculous meningitis in children are reported. The authors analyze the clinical features, CT scan findings, and clinical evolution. The criteria for and results of the use of cerebrospinal fluid shunts are reviewed.