MRI diagnosis of gliomatosis cerebri

Until recently the diagnosis of gliomatosis cerebri has been made on postmortem examination. This article reviews the use of serial magnetic resonance imaging studies to suggest premorbid diagnosis of this condition. The following is a case report of a 14-year-old female who had a subtotal cortical resection of tumor and several years later developed a progressive dementia. At postmortem examination the diagnosis of gliomatosis cerebri was made. Diffuse progressive white matter changes involving both hemispheres and brainstem, with increased thickness of the corpus callosum and without changes in cortical markings on T2-weighted magnetic resonance images, in this patient were highly suggestive of the diagnosis of gliomatosis cerebri.     

脑胶质瘤病的诊断和治疗

目的 探讨脑胶质瘤病的诊断和治疗方法。方法 回顾性分析自1994年至2004年在我院诊治的8例脑胶质瘤病患者的临床表现、检查结果、治疗方法和预后情况，结合国内外文献分析讨论。结果 经综合治疗，本组早期临床症状改善者7例，病情恶化1例。生存期至今最短9月，最长大于8年。结论 结合临床表现和MRI等相关检查，对脑胶质瘤病作出早期诊断，并综合利用手术、化疗和放疗能有效的延长患者的生存时间，提高生存质量。     

Assessment of proliferative potential in gliomatosis cerebri

Summary The proliferative potential of neoplastic cells in two cases of gliomatosis cerebri was investigated by a combined staining technique, a one-step silver colloid method for nucleolar organizer region-associated protein (AgNOR) and immunohistochemistry for fibrillary acidic protein (GFAP). The neoplastic cells in the two cases had an abnormal shape and showed positive GFAP immunostaining in their cytoplasm. The numbers of AgNORs were counted in central and peripheral lesions of the neoplastic field in each case. The mean AgNOR scores in neoplastic cells were almost the same as those of nonneoplastic astrocytes in both the central and the peripheral lesions. These values were almost equal to the AgNOR score of low-grade gliomas. These findings indicate that gliomatosis cerebri has an invasive character in the central nervous system and often shows a malignant tendency, but its proliferative potential is significantly lower than that of high-grade gliomas.     

Epilepsy surgery in children with gliomatosis cerebri

PURPOSE: Gliomatosis cerebri (GC) is a rare neoplastic disorder that may present as intractable epilepsy during early life. We report our experience regarding the evaluation and the surgical treatment of epilepsy in this population. METHODS: All children evaluated between 1990 and 2006 for surgery of epilepsy (n = 741) with pathologically proven GC were selected. RESULTS: We identified four male children with age at seizure onset ranging from 4 months to 11 years. Two had hemiparesis and one child with infantile spasms was developmentally delayed. Seizures occurred daily (n = 3) or monthly (n = 1). Ictal semiology was consistent with psychomotor seizures (n = 1), partial motor seizures (n = 2), and asymmetric epileptic spasms (n = 1). Surgery was symptomatic and aimed at debulking and controlling the epilepsy. Procedure was individually tailored based on the presurgical evaluation. Brain MRI revealed widespread hemispheric involvement (n = 3) or infiltration of the temporal lobe and basal ganglia (n = 1). Two patients were initially misdiagnosed as hemispheric cortical dysplasia and hemimegalencephaly. Scalp EEG was nonlocalizing in two cases, showed a right temporal focus in one case, and was not performed in one case. Interictal SPECT in one patient revealed widespread hemispheric hypoperfusion. Three cases were resected under ECoG guidance after a mean delay of 11 months after seizure onset. Following functional hemispherectomy (n = 1) or focal cortical resection (n = 2), all children were alive and seizure free with a mean follow-up of 48 months (2-5 years). No unexpected complication was reported. One nonoperated case was alive but still seizing after 15 months follow-up. Chemotherapy was associated in three cases. CONCLUSIONS: GC is a rare cause of medically resistant epilepsy that may present in early life. The lack of a discrete lesion may lead to diagnostic uncertainty, especially in infancy. Epilepsy surgery is an effective therapy that can improve quality of life.     

Genetic aberrations in gliomatosis cerebri support monoclonal tumorigenesis

Gliomatosis cerebri is a rare condition in which the brain is infiltrated by an exceptionally diffusely growing glial cell population involving at least 2 lobes, though often more extensive, sometimes even affecting infratentorial regions. The neoplastic proliferation may have a monoclonal origin, or alternatively, reflect progressive neoplastic change of an entire tissue field ("field cancerization"). The presence of an identical set of genetic aberrations throughout the lesion would point to monoclonality of the proliferation. In contrast, the finding of non-identical genetic changes in widely separated regions within the neoplasm would support the concept of field cancerization. In the present study, a unique autopsy case of gliomatosis was available to verify either one of these hypotheses. Tissue samples were randomly taken from 24 locations throughout the brain and used for genetic investigation. In all samples the histology showed an identical picture of slightly elongated astrocytic cells, typical for gliomatosis. TP53 exon 5-8 mutation analysis was performed on all samples. Genome-wide screening for chromosomal aberrations was accomplished by comparative genomic hybridization (CGH). In addition, loss of heterozygosity analysis for polymorphic markers on chromosomal regions of the 2 most frequently observed DNA deletions was carried out. The most widespread genetic aberration was mutation of exon 7 of TP53, which was detected in 20 of 24 samples. Bidirectional sequencing revealed a mutation in codon 234 (TAC234TGC), resulting in an amino acid substitution Tyr-Cys. CGH analysis revealed losses on 2q11-q31 in 13 of 24 samples and losses on 19q13-qter in 10 of 24 samples from both left and right hemispheres. Allelic imbalances for markers on 2q (2q14.3 and 2q22.1) and 19q (both 19q13.2) were demonstrated in 10 of 24 and 18 of 24 samples, respectively. Other widespread chromosomal aberrations included losses on 3q13-qter and 16q22-qter and gains on 7q22-qter. The wide distribution of a particular set of genetic aberrations in this case supports the concept of monoclonal tumor proliferation. The results point to involvement of TP53 mutation in the tumorigenesis of gliomatosis cerebri.     

大脑胶质瘤病的MRI特点研究

目的探讨大脑胶质瘤病的MRI特点。方法对14例经手术（或活检）、病理证实的大脑胶质瘤病患者的MRI和临床资料进行回顾性分析。结果大脑胶质瘤病的临床表现以头痛（12／14）和癫痫（7／141为常见，后期多出现严重颅高压征象。MRI提示病灶呈多灶性生长9例，弥漫性生长5例，至少累及2叶脑组织。T1WI呈等或稍低信号灶，T2WI为等或高信号灶，轻至中度水肿．占位效应轻。增强扫描常见肿瘤轻度强化。星形胶质瘤Ⅰ级7例，Ⅱ级5例．少枝胶质瘤Ⅱ级1例．少枝一星形混合胶质瘤Ⅱ级1例。结论大脑胶质瘤病的影像学表现与某些神经系统病变有类似和重叠之处．但通过影像与临床表现的结合，有利于该病变的诊断与鉴别诊断。     

Abnormal neuronal migration and gliomatosis cerebri in epidermal nevus syndrome

Summary A detailed neuropathologic examination of the brain of a child with the typical epidermal nevus syndrome revealed a primary disturbance of development of the brain. The developmental disturbance consisted of an abnormal or incomplete migration of neurons to form the cerebral and cerebellar cortices. The normal architectonic pattern of the cortical layer formation of the cerebrum and cerebellum was also disturbed. In addition, there was an abnormality in the proliferate activity of astroglial cells resulting in gliomatosis cerebri. It is suggested that the basic abnormality underlying various neurologic derangements in epidermal nevus syndrome is the result of a defect in specific development events, such as neuronal migration and cortical differentiation.Supported in part by NIEHS grant nos. 5RO 1-ES 01722 and ES 01247     

Epilepsia partialis continua associated with widespread gliomatosis cerebri

We report an uncommon association of intractable epilepsia partialis continua that was the main presentation of widespread gliomatosis cerebri in two females. Both children had a preceding prolonged secondary generalized seizure 2-4 months before the evolution of epilepsia partialis continua, including recurrent clusters of left-sided myoclonic twitching and sensory impairment. During these events, the children remained fully alert. These seizures were corroborated by prolonged focal epileptic spike/wave discharges evident on the electroencephalograms. Cerebral magnetic resonance imaging in the first patient demonstrated a wide area of increasing signals over the right frontocentral regions, along with diffuse cortical-subcortical infiltration impinging on the left hemisphere. In the second patient a cortical lesion was suspected. Evaluation for Rasmussen’s encephalitis, focal cortical dysplasia, or a gliomatous process was conducted; the patients underwent a stereotactic brain biopsy in which the histologic findings were compatible with gliomatosis cerebri with diffuse widespread infiltration of glioma cells with no constitution of a circumscribed tumor mass. The first patient was treated with cranial radiation, chemotherapy, steroids, and combined antiepileptic therapy. The focal seizures gradually but markedly decreased in frequency, and sensory impairment abated within 18 months after establishment of the diagnosis and ensuing therapy. Cognition remains intact. The second female died 2 years after presentation despite massive chemotherapy and antiepileptic medications. Although rare, gliomatosis cerebri should be taken into account in the differential diagnosis of epilepsia partialis continua in children to facilitate a rapid diagnosis and initiation of prompt treatment of this rare disorder that may respond to a concurrent effective combination of cranial radiation, chemotherapy, and antiepileptic medications.     

立体定向活检诊断大脑胶质瘤病(附17例临床分析)

目的探讨立体定向活检手术在大脑胶质瘤病诊断中的应用价值,提高大脑胶质瘤病的诊断水平。方法对影像学显示颅内病灶侵犯2个以上脑叶的患者行立体定向活检术。安装日本驹井式或Leksell立体定向头架,行CT或MRI增强扫描,利用"四点一线手算法"确定包含入颅点、靶点及靶点前后各10mm点共四个点的三维长轴,或采用计算机辅助立体定向手术系统(CAPN)计算靶点坐标及规划活检入颅。所取标本送病理学检查。结果经病理证实,17例诊断为大脑胶质瘤病,其中星形细胞瘤Ⅰ级3例,Ⅱ级8例,Ⅱ～Ⅲ级2例,Ⅲ级4例。未出现因活检手术而造成的出血、偏瘫等严重并发症。17例患者术后均给予相应的治疗。结论立体定向活检术对于明确诊断大脑胶质瘤病,具有重要的应用价值。     

经病理证实的大脑胶质瘤病的临床及影像特点

目的 研究大肭胶质瘤病的临床表现和影像学,以提高对该病的认识和诊断的准确性.方法 收集2006年12月至2009年6月海军总医院神经内科收治的经病理证实的10例大脑胶质瘤病患者,回顾性分析临床及神经影像学表现.结果 患者临床表现多样,有头痛、头晕、肢体力弱、智能减退、言语不清、癫癎等,但症状较轻.脑MRI表现弥漫,额叶、颞叶、顶叶、枕叶、胼胝体、丘脑、基底节、侧肭室旁白质、脑干、小脑有不同程度片状长或等T1及长T2信号,边界不清,无明显占位效应,3例有增强效应.病灶多为双侧多个脑叶广泛受累,无钙化、囊变和显著团块.8例弥散加权信号高低与病理级别正相关.7例MRI波谱分析表现为胆碱/肌酸和胆碱/N-乙酰天冬氨酸比值升高,胆碱/肌酸比值肿瘤实质区为1.28±0.15,正常脑组织为0.92±0.17,差异有统计学意义(t=4.201,P=0.0012,95%CI:0.17～0.57),胆碱/N-乙酰天冬氨酸肿瘤实质区为3.21±1.19,正常脑组织为0.61±0.18,差异有统计学意义(t=5.716,P=0.0001,95%CI:1.61～3.59).脑活体组织检查表现为弥漫性低级别星形胶质细胞瘤8例,高级别2例.结论 本病诊断需要注意影像学病变范围广泛以及临床与影像的不匹配,结合脑活体组织检查病理学以确诊.MRI波谱可提高对大脑胶质瘤病的诊断,弥散加权技术可提示肿瘤级别,帮助判断预后.     

Marked response of gliomatosis cerebri to temozolomide and whole brain radiotherapy

Gliomatosis cerebri (GC) represents an unfortunate, rare variant of glioma with a very poor prognosis. Given this lesion's rarity, little information exists on appropriate treatment options. The diffuse, infiltrative nature of GC precludes any surgical resection and limits therapy. Because of the improved survival seen with the use of temozolomide (TMZ) in malignant glioma, a rigorous systematic review of the published literature was performed to ascertain the benefit of TMZ in GC. We identified all GC cases in the literature where there was enough information to ascertain a clear response to a specific chemoradiotherapeutic treatment. In addition to our experience with a recent case, we have identified 61 patients with GC in the published literature who demonstrated a positive radiographic or clinic response after treatment. Statistical analysis of survival was performed by Kaplan-Meier analysis. A positive radiographic and clinical response was seen in patients ranging in age from 4 to 84 years. Overall median survival in patients diagnosed with GC who demonstrated a response after treatment was 25 months, with 1- and 2-year survival rates of 89% and 55%, respectively. The most common treatment regimens for responders included TMZ alone (26.2%), external whole-brain radiotherapy (WBRT) (26.2%), and concomitant TMZ and WBRT (20%). Our patient was treated with concomitant TMZ (150 mg/m(2)/day over 5 days) and WBRT (50 Gy) and has remained with a complete radiographic response after 36 months. In conclusion, patients with GC confirmed by surgical biopsy should be aggressively treated with concomitant TMZ and WBRT, as marked responses have been seen, and this appears to offer overall survival benefit.     

Intracranial hypertension as the first clinical manifestation of gliomatosis cerebri

A case of gliomatosis cerebri which clinically presented with a syndrome of intracranial hypertension (ICH), involvement of bilateral sixth cranial nerves, and oppressive holocranial headache of one week of evolution. Cranial MR and CT were performed demonstrating diffuse hypodense cortical-subcortical lesions on tomography and in T1 sequences and hyperdense lesions in T2 sequences with irregular contrast enhancement. Intracranial pressure was measured by ventricular catheter with the appearance of high, maintained pressure waves (Lundberg A waves). Ventricular LCR study and cerebral angiography did not provide additional data. Meningeal and cerebral biopsies showed infiltration by pleomorphous glioma leading to the diagnosis of gliomatosis cerebri. The patient was treated with steroids, hyperosmolar agents, external LCR derivation and tumoral radiotherapy. Nonetheless, the patient dies at six months of initiation of the symptoms. Gliomatosis cerebri should be taken into account in the differential diagnosis of clinical pictures presenting with ICH.