以中枢神经系统症状为首发HIV患者的临床特点

目的回顾性分析以中枢神经系统症状为首发表现HIV患者的临床特点。方法对2008年1月1日~2015年12月31日在南京脑科医院住院诊断HIV,具有以中枢神经系统症状为首发表现的39例患者的临床资料,进行回顾性分析研究。结果研究人群的平均年龄为40.9±9.4岁,平均CD4细胞计数为55cells/mm3(QR:25~105)。最常见的临床表现为头痛(87.2%),体重下降(71.8%),发热(66.7%)。弓形虫脑炎(28.2%)、艾滋病痴呆综合征(17.9%)、原发性中枢神经系统淋巴瘤(PCNSL)(15.4%)、不明原因的CNS感染(15.4%)和隐球菌脑膜炎(12.8%)、结核性脑膜炎(12.8%)、不明原因的颅内占位性病变(12.8%)是艾滋病毒相关的中枢神经系统疾病表现的主要病因。结论 HIV-相关的中枢神经系统疾病越来越常见,临床表现复杂多样,易误诊,应提高警惕,留意抗HIV抗体的筛查。     

Prolonged interval between sentinel pseudotumoral demyelination and development of primary CNS lymphoma.

Primary central nervous system lymphoma (PCNSL) can be associated with preceding demyelinating pseudotumoral brain lesions. The 'sentinel' demyelinating lesions recede spontaneously or with corticosteroid, and are followed by development of PCNSL typically within 12 months. This report describes a 29 year-old post-partum woman who developed PCNSL 4 years after a biopsy-proven pseudotumoral demyelinating episode. She presented with focal seizures in February 2005. She subsequently developed hemiparesis and raised intracranial pressure. MRI showed two contrast enhancing lesions in the right frontal lobe, which were hypermetabolic on (18)F-FDG PET. A provisional diagnosis of tumefactive multiple sclerosis was made. Symptoms recurred despite multiple courses of high dose corticosteroid. Brain biopsy confirmed large B-cell non-Hodgkin's lymphoma. This patient illustrates the importance of considering PCNSL in patients presenting with a space-occupying lesion, even with previously confirmed demyelination, and that the interval between the two events may be several years.     

AIDS-related focal brain lesions in the era of highly active antiretroviral therapy

OBJECTIVE: To compare the years since the introduction of highly active antiretroviral therapy (HAART) with the pre-HAART era for trends in the proportions of HIV-related focal brain lesion-causing disorders. METHODS: A prospective, single-center study of all consecutive HIV-infected patients with a neurologic presentation and focal brain lesions observed between January 1991 and December 1998 was undertaken. RESULTS: The major diagnoses in the 281 patients were toxoplasmic encephalitis (36.4%), primary CNS lymphoma (26.7%), progressive multifocal leukoencephalopathy (18.2%), and focal HIV encephalopathy (5.0%). During the HAART period, patients were less likely to be male, contracted HIV more often through heterosexual exposure, had fewer previous AIDS-defining events, received antiToxoplasma prophylaxis less frequently, had a CD4+ lymphocyte count 2.5 times higher, and had diagnosis based more often on PCR assays from CSF, reducing the need for brain biopsy and enhancing the likelihood of in vivo diagnosis. Using all patients hospitalized per year as reference population, the risk of focal brain lesions strongly increased during the pre-HAART period and declined significantly during the HAART years. In the HAART period a relevant decline of primary CNS lymphoma was found (OR for 1998, 0.25; p for trend = 0.03) and the effect of progressive calendar year was confirmed on multivariable analysis (OR, 0.52; 95% CI, 0.28 to 0.97). The frequency of toxoplasmic encephalitis decreased during the pre-HAART era and was stable afterwards. For progressive multifocal leukoencephalopathy, a slight increase was seen over time. Focal white matter lesions without enhancement or mass effect increased between 1991 and 1998. CONCLUSIONS: During the HAART era, AIDS-related primary CNS lymphoma showed a strong decline, toxoplasmic encephalitis remained stable, and progressive multifocal leukoencephalopathy showed a slight increase. Focal white matter lesions without mass effect or contrast enhancement became the most frequently seen focal brain lesion. For differential diagnosis, PCR-based assays from CSF led to a shift from brain biopsy toward a minimally invasive approach with an augmented likelihood of in vivo diagnosis.     

Sentinel lesions of primary CNS lymphoma.

Some patients ultimately diagnosed with primary CNS lymphoma (PCNSL) have transient symptomatic contrast enhancing lesions. These "sentinel lesions" of PCNSL recede spontaneously or with corticosteroid treatment and present an important diagnostic dilemma because they show variable, but non-diagnostic histopathological features. Four previously healthy, immunocompetent patients aged 49 to 58 years had contrast enhancing intraparenchymal brain lesions. Before biopsy, three of the four were treated with corticosteroids. Initial biopsies showed demyelination with axonal sparing in two, non-specific inflammation in one, and normal brain in one. Infiltrating lymphocytes predominantly expressed T cell markers with rare B cells. All four patients recovered within two to four weeks after the initial biopsy and imaging studies showed resolution of the lesions. The CSF was normal in three of the four patients tested; oligoclonal bands were absent in both of the two tested. After seven to 11 months, each patient developed new symptomatic lesions in a different region of the brain, biopsy of which showed a B cell PCNSL. The mechanism of spontaneous involution of sentinel lesions is not understood, but may represent host immunity against the tumour. Sentinel lesions of PCNSL should be considered in patients with contrast enhancing focal parenchymal lesions that show non-specific or demyelinative histopathological changes. Close clinical and radiographic follow up is essential if PCNSL is to be diagnosed early in such patients.     

立体定向活检诊断原发性中枢神经系统淋巴瘤(118例临床及影像学特征)

目的总结原发性中枢神经系统淋巴瘤(PCNSL)的临床、影像学特征,提高PCNSL诊治水平。方法回顾性分析经立体定向活检病理证实的118例PCNSL的临床和影像学资料。结果 118例PCNSL患者的病理类型均为B细胞性,其中男性73例,女性45例,男:女=1.62∶1,患者年龄11～83岁(平均53.4±15.9岁)。首发症状到确诊的时间为7d～3年(3.47±6.65个月),病程在3个月以内的占78.75%,其中57.5%的患者病程在1个月以内。本组病例最常见的症状包括高颅压症状(51.1%)和肢体功能障碍(47.7%)。单发病灶63例(53.4%),多发病灶55例(46.6%),基底节区和丘脑是最常见的受累部位。CT检查病灶多为稍高密度影,MRI检查病灶多为长T1、等或长T2信号影,多数病灶增强扫描为片状均匀强化。结论 PCNSL多发于中老年人,男性多见,病程短,单发病灶多见,但多发病灶的比例也较高,影像学检查病灶多均匀强化,病灶边界不清,但缺乏特异性,确诊需依赖于立体定向活检病理诊断。     

Neuroinflammation preceding primary central nervous system lymphoma (PCNSL) – Case reports and literature review

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extra-nodal non-Hodgkin’s lymphoma. Corticosteroids cause transient regression of PCNSL at the radiological and histological level. A growing number of case reports describe histologically confirmed neuroinflammation (sentinel lesions) heralding the development of PCNSL. We present two further cases of sentinel lesions contextualised by a review of past literature. Our aims are to collate existing knowledge on sentinel lesions in PCNSL and explore their pathophysiological significance. Two cases were identified (n = 2) from a cohort of 104 patients with PCNSL referred to a tertiary neurosurgery centre. A literature search identified previously reported cases (n = 14). Median age was 57.5 (range; 26–72); pre-biopsy corticosteroid administration was reported in 50% of cases (n = 8); mean time between biopsies was 10 months (range; 3–60). Common MRI features were homogenous enhancement (10;71.4%) and T2-hyperintensity (11;100%). Histochemical analysis of sentinel lesion biopsy revealed inflammatory CD3/4/5/8-positive T-cells (14; 100%), demyelination (13; 81.3%), rare/scattered CD20-postive B-cells (11;78.6%) and CD68-positive macrophages (10;71.4%). Repeat biopsy confirmed PCNSL in all cases. Waxing and waning CNS inflammation has been identified in 16 patients ultimately diagnosed with PCNSL. Neuro-specialists should be aware of this atypical presentation and maintain a high index of suspicion for lymphoma despite histopathology negative for lymphoma when clinical or radiological features indicate PCNSL.     

以进行性脑萎缩及非占位性脑白质病变起病的原发性中枢神经系统淋巴瘤(附1例报道及文献复习)

目的报道1例以进行性脑萎缩和颅内多发病变起病的原发性中枢神经系统淋巴瘤。方法收集1例经病理确诊为原发性中枢神经系统淋巴瘤患者的病史及体征、实验室检查、影像学检查、颅内立体定向穿刺活检病理结果,并结合文献复习进行分析。结果患者男性,29岁,因"进行性四肢震颤伴反应迟钝2年,双下肢无力1个月"入院。入院前MRI提示进行性加重的脑萎缩及颅内皮质下、侧脑室旁、基底节多发长T1长T2病灶。外院予甲泼尼龙冲击治疗,2个月后复查头颅MRI示原病灶缓解,左顶叶新发长T1短T2病灶,有占位效应。穿刺活检病理证实左顶叶病灶为弥漫大B细胞淋巴瘤。结论非占位性白质病变及脑萎缩在原发性中枢神经系统淋巴瘤中鲜见,肿瘤实质病灶出现前,其临床特点、影像学及激素治疗效果往往与脱髓鞘病变难以鉴别。因此临床医生需结合病史及影像学检查综合考量诊断,合理选择检查与治疗时机,重视临床随访。     

Epstein-Barr virus DNA load in cerebrospinal fluid and plasma of patients with AIDS-related lymphoma

Detection of Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid (CSF) is associated with acquired immunodeficiency syndrome (AIDS)-related brain lymphoma. Real-time polymerase chain reaction (PCR) was performed to quantify EBV DNA in CSF and plasma from 42 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Twenty patients had primary central nervous system lymphoma (PCNSL) and 22 systemic NHL, including 12 with central nervous system involvement (CNS-NHL). As controls, 16 HIV-infected patients with other CNS disorders were examined. EBV DNA was detected in the CSF from 16/20 (80%) patients with PCNSL, 7/22 (32%) with systemic NHL, 8/12 (67%) with CNS-NHL, and 2/16 (13%) of the controls. The viral EBV DNA levels were significantly higher in the CSF from patients with PCNSL or CNS-NHL compared to patients with systemic NHL or controls. EBV DNA was detected in plasma from 5/16 (31%) patients with PCNSL, 9/16 (56%) with systemic NHL, 4/9 (44%) with CNS-NHL, and 4/15 (27%) controls. No difference in plasma viral load was found between patient groups. From the patients with CNS-NHL, plasma samples drawn prior to CNS involvement contained significantly higher EBV DNA levels than those from systemic NHL patients without subsequent CNS involvement. EBV DNA levels in the CSF, but not in plasma, from patients treated with antiherpes drugs were significantly lower than in untreated patients. High CSF EBV DNA levels were found in HIV-associated brain lymphomas and the viral load can be clinically useful. High plasma EBV DNA levels might predict CNS involvement in systemic NHL.     

B Cell lymphoma of the brain stem masquerading as myasthenia

A 54 year old man is described with signs compatible with ocular myasthenia gravis and an apparent excellent response to pyridostigmine. Subsequent clinical progression and further investigation suggested the presence of an inflammatory brain stem lesion, which responded to corticosteroid therapy. Clinical relapse, including the development of central neurogenic hyperventilation, led to a brain stem biopsy, confirming a diagnosis of B cell lymphoma. This case illustrates the propensity of primary CNS lymphoma (PCNSL) to mimic other conditions. Brain MRI is mandatory in presumed "test negative" ocular myasthenia with atypical clinical findings. Spontaneous regression of PCNSL or response to corticosteroids is common and should not mitigate against the diagnosis. Histopathological confirmation should ideally be made before starting therapy, as this may obscure or delay the correct diagnosis. Although PCNSL is rare, it must be considered in all patients with brain stem syndromes, and in all patients 50 years or older with contrast enhancing focal lesions.     

Primary intracranial neoplasms in patients with HIV.

OBJECTIVE: To report a series of HIV-infected patients with intracranial tumors not known to be associated with immunodeficiency. BACKGROUND: The spectrum of HIV-associated diseases is changing with improved treatments and prolonged patient survival. Although primary central nervous system lymphoma (PCNSL) and toxoplasmosis continue to be the most common intracranial lesions in HIV-infected patients, the recognition of other pathologic entities is increasingly important. METHODS: The clinical characteristics and outcome of eight HIV-infected patients with nine intracranial neoplasms other than PCNSL are reported. In addition, all available pathologic specimens were tested for evidence of either HIV or Epstein-Barr virus (EBV) infection. An additional 28 patients reported in the literature are summarized. RESULTS: Five of eight patients had a glioblastoma multiforme; other tumors included an anaplastic ependymoma, a low-grade glioma, a subependymoma, and a leiomyosarcoma. More than half of the patients developed their tumor > or =6 years after the diagnosis of HIV infection. Patient prognosis and survival was best predicted by tumor histology. Treatment response and outcome did not appear to be influenced by HIV infection. Only the leiomyosarcoma demonstrated evidence of latent EBV infection. CONCLUSIONS: HIV-infected patients are at risk for intracranial neoplasms other than PCNSL, and benefit from aggressive tumor-specific therapy. It is possible that gliomas are occurring at a higher rate than in the general population. There was no evidence of HIV or EBV infection in any glial tumor.     

Lymphomatosis cerebri presenting as a rapidly progressive dementia: clinical, neuroimaging and pathologic findings

Primary central nervous system lymphoma (PCNSL) usually presents with clinical and neuroimaging findings consistent with single or multiple intracranial mass lesions. On cranial magnetic resonance imaging (MRI), such lesions are nearly always contrast enhancing, reflecting disruption of the blood-brain barrier at the site of tumor nodules. We describe 2 cases from the UCLA Medical Center who developed a rapidly progressive dementia due to extensive gray and white matter cerebral lesions involving much of the brain. In the patient who came to autopsy, widely infiltrating, focally necrotic B-cell plasmacytoid lymphoma was noted throughout the cerebral neuraxis. MRI findings in case 2 were consistent with diffuse lymphomatous brain infiltration without mass lesions, which was biopsy proven. We conclude that PCNSL may occur in a diffusely infiltrating form which may occur without MRI evidence of mass lesions or blood-brain barrier compromise. We refer to this entity as 'lymphomatosis cerebri' and add it to the differential diagnosis of a rapidly progressive dementia.     

Primary central nervous system lymphoma report of 32 cases and review of the literature

We retrospectively analyzed 32 cases of primary central nervous system lymphoma (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the period 1995-2002. There were 17 men and 15 women whose median age was 69 years. Three patients were immunodeficient. The commonest symptoms were focal deficit (16 patients) and cognitive/behaviour disturbances (14 patients). Radiologically, a total of 47 contrast-enhancing lesions were observed in 32 patients; 18 patients had deep-seated lesions. All but two patients underwent histological diagnosis following craniotomy (11 patients) and/or stereotaxic biopsy (22 patients); diagnosis was obtained on CSF cytology in one patient with a third ventricle tumour. In the last patient, the diagnosis was based on the finding of marked tumour shrinkage under corticotherapy, despite two negative histological examinations. Treatment included surgical resection (10 patients), chemotherapy (25 patients) and/or radiotherapy (12 patients). According to the therapeutic recommendations of the GELA (Groupe d'Etude des Lymphomes de l'Adulte), 19 patients received at least two courses of high-dose methotrexate; intrathecal chemotherapy was used in 20 patients with methotrexate and/or cytosine arabinoside. Radiation therapy consisted of whole brain irradiation followed by a boost on tumour site. Nine patients received a combined treatment of chemotherapy and radiotherapy. Twelve patients showed rapid progression to death. At the time of last contact, 28/32 patients (88%) had died, all from PCNSL disease or from complications due to its treatment. The median survival time was 13.9 months. We conclude that PCNSL is an increasingly frequent tumour. The diagnosis is obtained by stereotactic biopsy in the majority of cases. The prognosis appears dismal despite an intensive multidisciplinary therapeutic approach.     

Biology and treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that is restricted in distribution to the brain, leptomeninges, spinal cord, and intraocular compartments. Although PCNSL shares overlapping features with systemic lymphoma, recent studies also reveal a unique pattern of gene and protein expression in PCNSL. These findings have yielded new insights into the pathophysiology of the disease, as well as the identification of novel prognostic biomarkers. Immune system compromise, such as is seen in acquired immune deficiency syndrome (AIDS), is the best established known risk factor for PCNSL. Like other lesions of the brain, meninges, and eye, the presenting symptoms associated with PCNSL typically include focal neurological deficits related to the site of disease or more global consequences of increased intracranial pressure. Diagnosis of PCNSL typically includes gadolinium-enhanced MRI and pathologic tissue analysis, as well as additional studies aimed at excluding concurrent systemic disease. PCNSL typically has a worse overall prognosis than systemic lymphoma. High-dose chemotherapy, particularly with methotrexate-based regimens, is the backbone of therapy for most patients, and chemotherapy is associated with much lower rates of treatment-related morbidity and mortality than whole-brain irradiation. Autologous stem cell transplantation is an emerging treatment modality, particularly in younger patients with relapsed disease, but high rates of treatment-related mortality are observed in older patients. Immunotherapy, including treatment with intrathecal rituximab, is another area of active research that may have promise in refractory or relapsed disease. Treatment options for intraocular lymphoma parallel those for PCNSL elsewhere in the brain: systemic chemotherapy, radiation, and local delivery of cytotoxic and immunologically active agents such as anti-CD20 antibody.     

Primary CNS lymphoma: a whole-brain disease?

BACKGROUND: Autopsy studies reveal that most primary CNS lymphomas (PCNSL) extensively infiltrate the brain. To date, there has been no correlation of autopsy findings with a modern neuroimaging assessment of tumor burden. OBJECTIVE: To correlate autopsy findings in PCNSL to MRI findings. METHOD: From the authors' database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, 10 patients who died and had PCNSL at autopsy were identified. Their pathology was compared to MR scans obtained shortly before death. RESULTS: The median patient age was 60 years (range 44 to 80 years). There were six men and four women. Scans were performed within 4 weeks of death in seven patients, within 3 months in two patients, and within 4 months in one. Seven had enhancing lesions consistent with recurrence, and two of the three had focal T2 abnormalities. All had periventricular white matter abnormalities on T2 MR images. At autopsy, all 10 patients had widespread lymphoma throughout the CNS, but no tumor was found systemically. All had tumor infiltration in CNS regions that were normal radiographically, including T2 sequences. CONCLUSIONS: MRI underestimates the tumor burden of PCNSL. Bulky disease is seen as a contrast-enhancing lesion because of disruption of the blood-brain barrier, but microscopic tumor infiltration may lead to T2 hyperintensity or be completely normal radiographically.     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.     

Primary non-Hodgkin's malignant lymphoma of the central nervous system]

The incidence of primary central nervous system lymphoma (PCNSL) is increasing, not only in immunodeficiency states, but also in apparently normal individuals. The most common presentation of PCNSL is that of an intracranial mass lesion. Ocular involvement is associated in 20% of patients. CT/MR scan typically shows one or several periventricular tumors with indistinct margins that diffusely and densely enhance following contrast infusion. The diagnosis relies on lumbar puncture, vitreous biopsy, or stereotactic biopsy of a brain lesion demonstrating lymphomatous cells. If possible, corticosteroids should be used only after definite diagnosis. Corticosteroids have a cytotoxic effect responsible for transient remission in 40% of patients. Whole brain radiation therapy induces a complete or partial response in 80% of patients but recurrence always occurs and the median survival does not exceed 14-18 months. The addition of systemic and intrathecal chemotherapy seems to substantially improve the prognosis with median survival exceeding 3 years in some studies. PCNSL associated with AIDS generally occurs at a late stage of the disease and is the fourth cause of death in AIDS patients. Radiation therapy is useful but the median survival does not exceed 5.5 months because patients most often die of opportunistic infections.     

Primary lymphoma of the central nervous system: a clinical-pathological and immunohistochemical study of ten autopsy cases

CONTEXT: Primary central nervous system lymphomas (PCNSL) are a rare subgroup of lymphomas generally associated with HIV and EBV. OBJECTIVE: To study ten autopsy cases of PCNSL, to describe the neuropathological findings, to characterize the phenotype of the neoplastic cells, to detect EBV in the lesion and to compare the findings with the clinical and laboratory data of the patients. METHOD: The clinical, histological and immunohistochemical data of ten cases of PCNSL, eight cases from patients with AIDS, identified among 265 autopsies of these patients were analyzed. RESULTS: Seven patients were males and the mean age was 40.9 years. The most frequent symptomatology was focal neurologic deficit (70%). Six patients presented with only one lesion. Histologically, densely cellular and polymorphous neoplasms with angiocentrism were observed, in 90% of cases. An association with other diseases was observed in four cases. Most patients had diffuse large B cell non-Hodgkins lymphoma. EBV was detected by immunohistochemistry in only one case. The lack of detection of the virus might have been due to the long time of fixation of the brain which might have inactivate epitopes therefore compromising the testing. CONCLUSION: In the present series, PCNSL presented with focal symptoms, with unifocal or multifocal lesions, with a predominant B-cell CD20 positive phenotype, rarely associated with EBV.     

原发性中枢神经系统淋巴瘤的研究进展（英文）

Primary central nervous system lymphoma( PCNSL) is a rare form of non- Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors,definitive diagnosis requires brain biopsy,vitreoretinal biopsy,or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high- dose methotrexate- based chemotherapy regimens to whole- brain radiotherapy. Long- term survival,however,is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first- line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment,with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging,requiring collaborative efforts between institutions. This review highlights recent advances in the biology,detection,and treatment of PCNSL in immunocompetent patients.     

Absence of thallium-201 brain uptake in progressive multifocal leukoencephalopathy in AIDS patients

OBJECTIVE: To evaluate the presence of thallium-201 brain uptake determined by thallium-201 brain SPECT (Tl-201 SPECT) in patients with progressive multifocal leukoencephalopathy (PML) and AIDS. MATERIAL AND METHODS: Six AIDS patients with stereotactic biopsy diagnosis of PML were prospectively evaluated with Tl-201 SPECT, Magnetic Resonance Imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS). Tl-201 SPECT results were compared with 2 patients with AIDS and biopsy proven primary CNS lymphoma. RESULTS: In all patients with PML, Tl-201 SPECT studies showed lack of uptake while MRI demonstrated subcortical white matter focal brain lesions and 1H-MRS disclosed metabolic abnormalities. Intense thallium uptake (uptake ratios of 3.2 and 5.6) was demonstrated in the 2 patients with primary CNS lymphoma. CONCLUSIONS: The present study shows that PML lesions are not detectable on Tl-201 SPECT while MRI and 1H-MRS demonstrate abnormalities, and intense thallium-201 uptake may be detected in primary CNS lymphoma. These results suggest that Tl-201 SPECT is a method which, combined with other non-invasive techniques such as MRI and 1H-MRS, may help in the diagnostic approach of PML and to differentiate PML from other high proliferative brain lesions characterized by positive thallium uptake.     

Changing pattern of primary cerebral lymphoma in the highly active antiretroviral therapy era

Before the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL) represented one of the most prevalent causes of focal brain lesions in HIV-infected people. The prognosis of PCNSL was very poor, with median survival time not exceeding 2 months. Brain biopsy was the method of choice for the definitive diagnosis, but it was and remains an invasive procedure with morbidity and mortality as well as considerable costs in terms of patients' management and quality of life. The strict association between AIDS-PCNSL and Epstein-Barr virus led to the suggestion that EBV DNA in cerebrospinal spinal fluid (CSF) might serve as a diagnostic marker, reducing the time required for diagnosis and allowing a minimally invasive approach. The clinical usefulness of this methodology has been largely demonstrated through clinical practice. After the introduction of HAART in clinical practice, a survival benefit has been observed for most persons with acquired immunodeficiency syndrome (AIDS)-associated opportunistic infections and cancers. In particular, for patients with non-Hodgkin lymphoma, a higher likelihood of response to chemotherapy as well as a longer survival has been found as a consequence of the use of combined antiretroviral therapy. Although larger studies did not show significant changes in survival of HIV-infected patients with PCNSL in the era of HAART, small case series and anecdotal reports showed the benefit of HAART in the treatment of PCNSL. Nevertheless, these patients' survival still remains very poor and it could be hypothesized that, other than specific cancer prognostic determinants and severe immunodeficiency, viral pathogenesis as well as EBV-specific immunologic dysfunction may be responsible.