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.     

室管膜型原发性中枢神经系统淋巴瘤四例:临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤(PCNSL)的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果 4例患者平均发病年龄为44岁,发病至就诊时间13 d～5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征(2例)、多组脑神经麻痹(1例)和偏瘫(1例);病程中有间断低热(3例)。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力(2例)、白细胞计数(4例)和蛋白定量(4例)升高,葡萄糖降低(3例)。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶(2例)和鞍区病变(1例)。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

室管膜型原发性中枢神经系统淋巴瘤四例：临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤（PCNSL）的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果4例患者平均发病年龄为44岁,发病至就诊时间13d-5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征（2例）、多组脑神经麻痹（1例）和偏瘫（1例）;病程中有间断低热（3例）。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力（2例）、白细胞计数（4例）和蛋白定量（4例）升高,葡萄糖降低（3例）。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶（2例）和鞍区病变（1例）。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

Malignant non-Hodgkin lymphoma presenting with Garcin's syndrome

INTRODUCTION: R Garcin described progressive unilateral cranial nerve palsy in 1926. Garcin syndrome is characterized by progressive involvement of the cranial nerves culminating in total unilateral paralysis of all cranial nerves. Carcinoma of the skull base or ENT regions is the most common etiology. CASE REPORT: A 74-year-old man developed signs involving the left Vth (V2 and V3) cranial nerve then the VIth, VIIth and VIIIth cranial nerves and finally the IXth and Xth. MRI showed involvement of these cranial nerves with gadolinium uptake and involvement of the pons at the terminal phase. Careful ENT explorations failed to reveal a cause. The lymphocyte count was elevated in the cerebrospinal fluid. The patient died one year after diagnosis and the general autopsy was normal. The neuropathological studies led to the post-mortem diagnosis of type B non-Hodgkin lymphoma. CONCLUSION: In patients with Garcin syndrome, lymphoma is a possible diagnosis when carcinoma of the ENT regions or of the skull bases are not present.     

Superficial cerebral and spinal haemosiderosis caused by secondary tethered cord syndrome after resection of a spinal lymphoma

Superficial haemosiderosis results from chronic subarachnoid haemorrhage during which haemosiderin is deposited in the leptomeninges around the brain, spinal cord and cranial nerves. We describe an exceptional case of superficial haemosiderosis characterised by two special aspects. (1) The cause was a secondary tethered cord syndrome due to dural adhesions which had developed 8 years after resection of a thoracic lymphoma and (2) an explorative neurosurgical procedure with complete untethering caused normalisation of the cerebrospinal fluid and stopped disease progression.     

A case of multiple cranial nerve palsy with severe dysphagia due to herpes zoster infection]

A case of multiple cranial nerve palsy by herpes zoster was reported. A 79-year-old man showed fever, sore throat, and dysphagia. No vesicle was noted at ear and pharynx. The patient developed, later, left peripheral facial nerve palsy. The cerebrospinal fluid revealed pleocytosis with increased protein. The viral antibody titer of herpes zoster was significantly elevated both in cerebrospinal fluid and in serum. The left facial palsy was slightly improved. But his dysphagia didn't improve during at least 10 months after the onset. Among the cranial nerves, trigeminal and facial nerves are the most commonly affected by herpes zoster. But there are a few cases of the 9th and 10th cranial nerve involvement in the literature. However, dysphagia has rarely been reported in these previous cases, only four cases developed severe dysphagia like the present patient. All of these cases including our case were over sixty years old, while cases with slight dysphagia were under sixty years old. No other differentiating factor is noted between these two groups with regard to sites of vesicles, findings of cerebrospinal fluid and mode of therapy.     

Jugular foramen syndrome caused by varicella zoster virus infection in a patient with ipsilateral hypoplasia of the jugular foramen

We report a patient with acute cranial polyneuropathy with unilateral involvement of the ninth, tenth, and eleventh cranial nerves. Although this patient lacked a typical cutaneous herpetic manifestation, elevated levels of IgM and IgG antibodies to varicella zoster virus (VZV) in both the serum and cerebrospinal fluid confirmed the clinical diagnosis of VZV infection and zoster sine herpete. Coexisting hypoplasia of the ipsilateral jugular foramen was detected using three-dimensional, surface-rendering displays reconstructed from the cranial helical CT scan. The patient recovered almost completely following treatment with an anti-inflammatory corticosteroid. Anatomical narrowing of the jugular foramen in this patient may have contributed to entrapment of the affected nerves at their passage through the foramen.     

Lower cranial nerve involvement as the initial manifestation of Lyme borreliosis

Lyme disease or Lyme borreliosis is an infectious disease transmitted by ticks and caused by Borrelia burgdorferi. Being clinically different from Relapsing Fever it may cause an array of symptoms, specially cutaneous and neurological but also musculoskeletal and cardiac ones. Within the neurologic manifestations of Lyme disease the affectation of low cranial nerves is, to our knowledge, extremely infrequent. We present the clinical case of a 35 years old male whose initial symptoms were low cranial nerve dysfunction with a cerebrospinal fluid compatible with meningitis. Serology against Borrelia burgdorferi both in serum and cerebrospinal fluid was positive.     

Pituitary tumour as a presenting symptom of a systemic lymphoma

Pituitary non Hodgkin malignant lymphomas are rare. We report a case of large cell systemic lymphoma with pituitary and meningeal localizations in a 40-year-old patient. The clinical picture was panhypopituitarism with MRI appearance of pituitary adenoma and VII and VIII cranial nerves involvement. Diagnosis was made by identification of lymphomatous cells in CSF. The patient deceased in less than one year despite chemotherapy.     

Cranial computed tomography of 64 children in continuous complete remission of leukemia I: relations to therapy in modalities

64 children with acute lymphoblastic leukemia and non Hodgkin's lymphoma in continuous complete remission were studied by cranial computed tomography two months to 7 years after cessation of antileukemic treatment. 17 (27%) patients showed abnormal widening (grade 2) of external cerebrospinal fluid spaces, 20 (31%) minimal widening (grade 1). A significant correlation between grade 2 abnormalities and the duration of maintenance therapy and single cranial radiation dose was found, whereas the correlations with total radiation dose and with intensity of induction protocols were not significant. Widening of external cerebrospinal fluid spaces after cessation of therapy persisted.     

磁共振断层血管成像在颅神经血管压迫综合征的应用

目的 探讨磁共振断层血管成像(MRTA)对颅神经血管压迫综合征病因诊断的临床应用价值,评价3D-FIESTA及3D-TOF-SPGR序列显示颅神经与血管的三维空间关系的能力.方法 湖北省恩施自治州中心医院神经外科白2007年5月至2009年5月共收治行微血管减压术(MVD)治疗的颅神经血管压迫综合征患者41例,术前行MRTA及其3D-FIESTA和3D-TOF-SPGR 序列扫描,观察颅神经与周围血管的空间关系,并与术中探查结果进行对照,评价MRTA及其3D-FIESTA和3D-TOF-SPGR序列在术前评估颅神经与周围血管关系的能力.结果MRTA能清晰且同时显示三叉神经、面神经、舌咽神经等颅神经和责任血管,在3D-FIESTA图像上,脑脊液呈高信号,神经与血管呈中等信号,对比良好;在3D-TOF-SPGR图像上,脑脊液为低信号,脑实质和颅神经为等信号,血管为高信号;3D-FIESTA序列扫描显示病变侧神经与血管有密切关系34例(82.9%),3D-TOF-SPGR序列扫描显示病变侧神经与血管有密切关系35例(85.4%),二者差异无统计学意义(χ2=0.091.P=0.762).结论 MRTA技术能清楚显示颅神经及责任血管,3D-FIESTA结合3D-TOF-SPGR对颅神经血管压迫综合征的术前病因诊断及手术适应证的选择具有重要价值.     

颞下入路显微手术治疗哑铃型三叉神经鞘瘤

目的探讨颅底颞下-天幕入路显微手术治疗哑铃型三叉神经鞘瘤的效果。方法回顾性分析2003年1月至2012年12月采用颅底颞下-天幕入路显微手术治疗的28例哑铃型三叉神经鞘瘤的临床资料。结果肿瘤全切除23例（82.1%）,次全切除4例,大部分切除1例。术前22例面部麻木、感觉减退患者中,术后16例（72.7%）获得不同程度缓解。术前20例颅神经麻痹者中,术后16例（80%）获得不同程度好转。术前伴有颅内压增高症状、锥体束征、小脑征及面部疼痛者术后均获得缓解。12例患者获得5个月∽7年的随访,5例未全切除患者中复发2例。结论颅底颞下-天幕入路具有路径短,暴露充分,创伤小,易于达到一期全切等优点,适合于绝大多数哑铃型三叉神经鞘瘤的手术治疗。     

磁共振断层血管成像在颅神经血管压迫综合征的应用

目的 探讨磁共振断层血管成像(MRTA)对颅神经血管压迫综合征病因诊断的临床应用价值,评价3D-FIESTA及3D-TOF-SPGR序列显示颅神经与血管的三维空间关系的能力.方法 湖北省恩施自治州中心医院神经外科白2007年5月至2009年5月共收治行微血管减压术(MVD)治疗的颅神经血管压迫综合征患者41例,术前行MRTA及其3D-FIESTA和3D-TOF-SPGR 序列扫描,观察颅神经与周围血管的空间关系,并与术中探查结果进行对照,评价MRTA及其3D-FIESTA和3D-TOF-SPGR序列在术前评估颅神经与周围血管关系的能力.结果MRTA能清晰且同时显示三叉神经、面神经、舌咽神经等颅神经和责任血管,在3D-FIESTA图像上,脑脊液呈高信号,神经与血管呈中等信号,对比良好;在3D-TOF-SPGR图像上,脑脊液为低信号,脑实质和颅神经为等信号,血管为高信号;3D-FIESTA序列扫描显示病变侧神经与血管有密切关系34例(82.9%),3D-TOF-SPGR序列扫描显示病变侧神经与血管有密切关系35例(85.4%),二者差异无统计学意义(χ2=0.091.P=0.762).结论 MRTA技术能清楚显示颅神经及责任血管,3D-FIESTA结合3D-TOF-SPGR对颅神经血管压迫综合征的术前病因诊断及手术适应证的选择具有重要价值.     

The peripheral cerebrospinal fluid outflow pathway – physiology and pathophysiology of CSF recirculation: A review and hypothesis

An anatomical connection from subarachnoid spaces along nerves into peripheral tissues represents an important route for CNS antigens release, termed here peripheral cerebrospinal fluid outflow pathway (PCOP), is assumed analogous to mammals in humans: CSF leaves the subarachnoid spaces along nerves and joins respective interstitial tissue fluids, then the lymph then blood; in detail, flowing from the subfrontal subarachnoid spaces through the cribriform plate near olfactory nerves to nasal submucosa to the cervical lymph system, along cranial nerves and spinal nerves into respective peripheral tissues. Microanatomic details and relative shares of outflow volumes at various parts of the PCOP as compared to CSF reabsorption volumes into the venous system remain to be determined.Beyond, CSF functions as a third signaling system involving all CNS structures preferably surfaces, including spinal cord and nerve roots. But CSF may interact also with all cranial and peripheral nerves via the PCOP, and related peripheral tissues connected by nerves, e.g. subcutaneous tissues, muscles or neuronal ganglia, and even, a special case, the eye. PCOP associated pathomechanisms might arise with any abnormal pathogenic CSF contents including solutes and cells in various diseases, relevant especially in acute neuroinflammation, possibly in systemic inflammation, likely in chronic neuroinflammation and possibly in low level neuroinflammation. The latter may include subgroups of psychiatric disorders. PCOP associated pathomechanisms might explain for example the surprising muscle involvement in depression and schizophrenia, or diffuse pain or dysautonomia. PCOP associated pathomechanisms should generally relate to PCOP anatomy and the CSF outflow physiology respectively pathophysiology.     

Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP.

To date, high human T-cell lymphotropic virus type I proviral load in patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal fluid has not been well investigated. We measured human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis patients using real-time quantitative polymerase chain reaction (TaqMan). Human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T-cell lymphotropic virus type I Tax-specific CD8+ T cells, as detected by peptide-loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus-specific CD8+ T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T-cell lymphotropic virus type I-infected cells and preferential expansion of human T-cell lymphotropic virus type I-specific CD8+ cells in cerebrospinal fluid may play a role in the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.     

磁共振断层血管成像在颅神经血管压迫综合征的应用

目的 探讨磁共振断层血管成像(MRTA)对颅神经血管压迫综合征病因诊断的临床应用价值,评价3D-FIESTA及3D-TOF-SPGR序列显示颅神经与血管的三维空间关系的能力.方法 湖北省恩施自治州中心医院神经外科白2007年5月至2009年5月共收治行微血管减压术(MVD)治疗的颅神经血管压迫综合征患者41例,术前行MRTA及其3D-FIESTA和3D-TOF-SPGR 序列扫描,观察颅神经与周围血管的空间关系,并与术中探查结果进行对照,评价MRTA及其3D-FIESTA和3D-TOF-SPGR序列在术前评估颅神经与周围血管关系的能力.结果MRTA能清晰且同时显示三叉神经、面神经、舌咽神经等颅神经和责任血管,在3D-FIESTA图像上,脑脊液呈高信号,神经与血管呈中等信号,对比良好;在3D-TOF-SPGR图像上,脑脊液为低信号,脑实质和颅神经为等信号,血管为高信号;3D-FIESTA序列扫描显示病变侧神经与血管有密切关系34例(82.9%),3D-TOF-SPGR序列扫描显示病变侧神经与血管有密切关系35例(85.4%),二者差异无统计学意义(χ2=0.091.P=0.762).结论 MRTA技术能清楚显示颅神经及责任血管,3D-FIESTA结合3D-TOF-SPGR对颅神经血管压迫综合征的术前病因诊断及手术适应证的选择具有重要价值.     

Neurologic evaluation of non-Hodgkin's lymphoma in adult patients: a prospective study

This prospective study included 67 adult patients with low, intermediate or high malignancy degrees of non-Hodgkin's lymphomas according to the Working Formulation. Patients with or without anti-HIV antibodies in the serum were considered. All patients were submitted to neurologic evaluation, and 63 of them to examination of the cerebrospinal fluid (CSF). Patients presenting neurologic signs and symptoms were 42 (62.7%). Neurologic findings and CSF changes were correlated. The association of localized thoraco-lumbar pain and CSF changes (presence of neoplastic cells, increased protein concentration and/or increased gamma globulin content) was statistically significant, as the association of abnormal muscle strength in the lower limbs and CSF changes in patients without HIV antibodies in the serum. Cranial nerve dysfunction (III, IV and VI cranial nerves) correlated with the finding of neoplastic cells in the cerebrospinal fluid.     

吉兰-巴雷综合征的MRI诊断

目的 分析吉兰-巴雷综合征(OBS)患者的MRI扫描特征和限度. 方法对15例GBS患者(急性14例、慢性1例)行MRI平扫和增强后脂肪抑制TIWI扫描,观察椎管内周围神经的MRI表现及其与临床特征的关系.结果 MRI平扫显示8例急性患者马尾神经不同程度的增粗,T1WI为中等信号,T2W1为等或略高信号,1例慢性患者全脊椎的脊神经和马尾神经增粗.增强扫描显示14例急性患者T<,8>以下出现部分脊神经和马尾神经不同程度的增粗、强化,其中2例伴有部分颈脊神经增粗、强化,2例伴有部分颅神经增粗、强化.1例慢性患者全脊椎的脊神经、马尾神经和部分颅神经增粗、强化;全部患者出现双下肢乏力,其中双下肢瘫痪9例,MRI增强扫描均显示马尾神经明显强化(100%);双上肢乏力7例,MRI阳性3例(43%);颅神经功能障碍6例,MRI阳性3例(50%).结论 MRI可以敏感检测GBS患者的马尾神经病变,但颈神经和颅神经受累易漏诊.     

带状疱疹脑炎的临床及CSF特点

目的　研究带状疱疹脑炎 (HZAE)的临床表现及脑脊液 (CSF)特点。方法　对 7例HZAE患者的临床表现及CSF检查进行回顾性分析。结果　本组HZAE临床表现无特异性 ,其中典型皮疹、多脑神经损害为相对特征的临床表现 ,CSF细胞学表现淋巴样细胞反应 ,未见红细胞。结论　HZAE是一种临床少见的病毒性脑炎 ,CSF检查及相对特征的临床表现对本病的诊断有重要价值。     

Neurosarcoidosis: a review of its intracranial manifestation

Sarcoidosis is a multisystem disease of unknown cause and with a worldwide distribution. Involvement of the central nervous system occurs in a relatively small number of patients with sarcoidosis. Isolated neurosarcoidosis without signs of systemic disease is a rarity. Because of its non-specific clinical presentation and neuroradiological imaging characteristics, intracranial neurosarcoidosis remains a very difficult diagnosis, particularly in the absence of systemic signs of the disease. Intracranial neurosarcoidosis has a predilection for the basal leptomeninges commonly affecting the cranial nerves, but any part of the brain may be involved, resulting in a wide spectrum of clinical syndromes. Cranial nerve involvement is the most common single symptom. Intracranial sarcoid manifests as nodular or diffuse leptomeningeal thickening and extra- or intra-axial parenchymatous lesions. Intracranial sarcoid may mimic various forms of meningitis, including carcinomatous and intracranial mass lesions such as meningioma, lymphoma and glioma, based on neuroradiological imaging. Magnetic resonance imaging is a very sensitive diagnostic tool for detecting intracranial abnormalities due to neurosarcoidosis. Lumbar puncture is useful in ruling out other neurological disorders, in particular infectious, but cerebrospinal fluid findings are not specific. Angiotensin-converting enzyme in serum and cerebrospinal fluid may be increased, decreased or normal. Therapy consists of immunosuppressive agents and should be initiated with corticosteroids. Other immunosuppressive drugs should be added in severe cases or after frequent recurrences. We review here all aspects of intracranial neurosarcoidosis from the clinical point of view, with special emphasis on presentation, diagnostic procedures, differential diagnostic considerations and treatment. Received: 18 August 2000 / Received in revised form: 14 November 2000 / Accepted: 17 November 2000