- Case report
Long survival of primary diffuse leptomeningeal gliomatosis following radiotherapy and temozolomide: case report and literature review
European Journal of Medical Research volume 16, Article number: 415 (2011)
Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare neoplasm with a short survival time of a few months. there is currently no standardized therapeutic approach for PDLG.
Materials and methods
We report on a 53-year-old male patient who presented with epileptic seizures, gait disturbance, paraparesis and sensory deficits in the dermatomes T8-10.
Magnetic resonance imaging (MRI) revealing numerous spinal and cranial gadolinium-enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with WHO grade III astrocytic cells. Consecutively, the patient underwent craniospinal radiotherapy (30 Gy) and 11 sequential cycles of temozolomide. This regimen led to partial tumor regression. Thirteen months later, spinal MRI revealed tumor progression. Second-line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration. The patient died twenty-two months after diagnosis, being the longest survival time described thus far with respect to PDLG consisting of astrocytic tumor cells.
Radiochemotherapy including temozolomide, as established standard therapy for brain malignant astrocytomas, might be valid as a basic therapeutic strategy for this PDLG subtype.
Primary diffuse leptomeningeal gliomatosis (PDLG) is diagnosed when a glioma is located in the subarachnoid space, while intraparenchymal tumor lesions are absent . PDLG must be distinguished from secondary meningeal gliomatosis resulting from a primary gliomatous CNS tumor. PDLG occurs frequently along the spinal cord . PDLG, especially when caused by malignant astrocytic cells, is associated with very poor survival . A standardized therapy for patients with PDLG is lacking .
We describe a patient with PDLG consisting of malignant astrocytic cells who underwent combined radio- and chemotherapy leading to the longest survival time described in the literature thus far.
A 53-year-old man was referred to the Dept. of Neurology due to a generalized epileptic seizure and five months later he presented with bilateral sensory deficits at dermatome levels T8-10, paraparesis and gait disturbance. Cerebrospinal fluid (CSF) analysis revealed a high cell count (300/3 cells/μl; reference range: 5/3 cells/μl) with atypical cells that could not be further characterized. T1-weighted images (T1-WI) revealed spinal and cranial Gd-enhancing nodules in the leptomeninges (Figures 1a-e) and on T2-weighted images (T2-WI) an intramedullary edema (Figure 1c).
Three weeks later, intradural biopsy from a Gd-enhancing nodule at L2-3 level revealed fibrously-thickened meninges infiltrated by malignant astrocytic tumor cells (Figures 2a-c). the tumor was categorized as primary diffuse leptomeningeal gliomatosis (PDLG) confirmed by the Reference Center for Brain Tumors in Düsseldorf, Germany.
Prior to radiotherapy of the craniospinal axis (4 × 2.5 Gy/week, total dose: 30 Gy), the patient underwent 3 cycles of temozolomide (TMZ) (cycle 1: 150-200 mg/m2 TZM, d1-5, q28d). On re-staging, spinal T1-weighted images showed tumor-lesion regression on L5 and spinal T2-WI images demonstrated spinal-edema regression (compare Figures 1c-d with Figures 1a-b). Three weeks after the completion of radiotherapy the patient received eight additional cycles of TMZ (200 mg/m2 TZM, d1-5, q28d), during which meningeal thickening of the brain regressed. However, spinal MRI thirteen months after starting TMZ therapy revealed meningeal tumor progression at the lesions on spinal levels C1-2, C7-t2 and T5-8. Five cycles of second-line chemotherapy with irinotecan and bevacizumab failed to halt further clinical deterioration. the patient died twenty-two months after the diagnosis of PDLG and exhibited until dead an encouraging Karnovsky performance status of 60%. an autopsy was declined.
The diagnosis of PDLG is usually established by autopsy but rarely diagnosed prior to death . PDLG of the oligodendroglial and that of the well-differentiated astrocytic tumor type are associated with a considerably longer median survival time than that of the malignant astrocytic tumor type .
PDLG was diagnosed in the aforementioned case, as we observed on histopathology leptomeningeally-encapsulated malignant astrocytic cells without primary attachment to the spinal cord or brain parenchyma and Gd-enhancing leptomeningeal thickening at the base of the brain and spinal level in MRI [6, 7].
Various treatment modalities were used for 14 patients suffering from PDLG with malignant astrocytic cells reported in the literature so far (cf. Table 1), demonstrating the lack of a standardized treatment regimen of PDLG with malignant astrocytic cells. Although the number of cases is small, the data on their survival times (cf. Table 2) might suggest that radiotherapy and temozolomide (TMZ) as established treatment for newly diagnosed recurrent anaplastic astrocytomas  also seem to be valid for PDLG with malignant astrocytic cells. This concept is supported by the observation that radiotherapy alone can prolong the median survival time of five months for patients without any specific therapy to a median survival of 12 months and that integration of TMZ in the chemotherapy alone may lead to a prolonged median survival of 15 months. The importance of TMZ in the chemotherapy treatment of PDLG is supported by the observation that the median survival time fell to 3 months when the integration of TMZ was omitted.
The prolonged survival of our patient may be due to the addition of TMZ to radiation therapy as it resulted in an extent of the median survival time for high grade glioma patients . In addition, the hypofractionated radiotherapy regimen used is supposed to be more effective than conventional fractionated irradiation. Additionally, the patient's good Karnofsky performance status may have contributed to our patient's prolonged survival.
In conclusion, we report on partial regression and long survival in a patient with PDLG of the malignant astrocytic type following hypofractionated radiotherapy and TMZ. An immediate radiochemotherapy seems crucial for a prolonged survival of PDLG patients in good general condition.
Conflict of interests
The authors disclose no or potential conflict of interest including any financial, personal or other relationships with other people or organizations within the three years of beginning the submitted work that could inappropriately influence or be perceived to influence their work.
Bhatia R, Roncaroli F, Thomas P, Cheah SL, Mehta A, Glaser M, Ulbricht C: A case of primary leptomeningeal gliomatosis confined to the spinal cord. J Neurooncol 2010,98(1):125–9. 10.1007/s11060-009-0050-y
Barborie A, Dunn EM, Bridges LR, Bamford JM: Primary diffuse leptomeningeal gliomatosis predominantly affecting the spinal cord: case report and review of the literature. J Neurol Neurosurg Psychiatry 2001,70(2):256–258. 10.1136/jnnp.70.2.256
Riva M, Bacigaluppi S, Galli C, Citterio A, Collice M: Primary leptomeningeal gliomatosis: case report and review of the literature. Neurol Sci 2005,26(2):129–134. 10.1007/s10072-005-0446-1
Davila G, Duyckaerts C, Lazareth JP: Diffuse primary leptomeningeal gliomatosis. J neurooncol 1993,15(1):45–9. 10.1007/BF01050262
Debono B, Derrey S, Rabehenoina C, Proust F, Freger P, Laquerriere A: Primary diffuse multinodar leptomeningeal gliomatosis. Case report and review of the literature. Surg neurol 2006,65(3):273–282. 10.1016/j.surneu.2005.06.038
Davis PC, Friedman NC, Fry SM, Malko JA, Hoffmann JC Jr, Braun IF: Leptomeningeal metastasis: MR imaging. Radiology 1987,163(2):449–454.
Vertosick FT, Selker RG: Brain stem and spinal metastases of supratentorial glioblastoma multiforme- a clinical series. Neurosurgery 1990,27(4):516–522. 10.1227/00006123-199010000-00002
Omar A, Mason WP: Temozolomide: the evidence for its therapeutic efficacy in malignant astrocytomas. Core Evid 2009, 4: 93–111.
Stupp R, Mason WP, Van de Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisen-hauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain tumor and Radio-therapy groups; national Cancer Institute of Canada Clinical trials group.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005,352(10):987–996. 10.1056/NEJMoa043330
Rees JH, Balakas N, Agathonikou A, Hain SF, Giovanni G, Panayiotopolous CP, Luxsuwong M, Revesz T: Primary diffuse leptomeningeal gliomatosis simulating tuberculous meningitis. J Neurol Neurosurg Psychiatry 2001,70(1):120–122. 10.1136/jnnp.70.1.120
Dietrich PV, Aapro MS, Rieder A, Pizzolato GP: Primary diffuse leptomeningeal gliomatosis (PDLG): a neoplastic cause of chronic meningitis. J Neuroncol 1993,15(3):275–283. 10.1007/BF01050075
Tsui EY, Loo KT, Mok CK, Yuen MK, Cheung YK: Primary multifocal leptomeningeal gliomatosis. Eur J Radiol 2001,37(1):5–7. 10.1016/S0720-048X(00)00220-5
Jicha GA, Glantz J, Clarke MJ, Lehwald LM, Russo DP, Giannini C, Wald JT, Uhm J, Kumar N, Aksamit AJ, Wetmore CJ: Primary diffuse leptomeningeal gliomatosis. Eur neurol 2009,62(1):16–22. 10.1159/000216838
Franceschi E, Cavallo G, Scopece L, Esposti RD, Paioli G, Paioli A, Palmerini E, Foschini MP, Marliani AF, Crino L: Temozolomide-induced partial response in a patient with diffuse leptomeningeal gliomatosis. J Neurooncol 2005,73(3):261–264. 10.1007/s11060-004-5672-5
Heye N, Iglesias JR, Tönsen K, Graef G, Maier-Hauff K: Primary leptomeningeal gliomatosis with predominant involvement of the spinal cord. Acta Neurochir 1990,102(34):145–8.
Singh M, Corboy JR, Stears JC, Kleinschmidt-DeMasters BK: Diffuse leptomeningeal gliomatosis associated with multifocal CNS infarcts. Surg Neurol 1998,50(4):356–362. 10.1016/S0090-3019(97)00371-6
Yomo S, Tada T, Hirayama S, Tachibana N, Otani M, Tanaka Y, Hongo K: A case report and review of the literature. J Neurooncol 2007,81(2):209–216.
Pingi A, Trasimeni G, Di Basi C, Gualdi G, Piazza G, Corsi F, Chiappetta F: Diffuse leptomeningeal gliomatosis with osteoblastic metastases and no evidence of intraaxial lesions. AJNR 1995,16(5):1018–1020.
Kastenbauer S, Danek A, Klein W, Yousry TA, Bise K, Reifenberger G, Pfister HW: Primary diffuse leptomeningeal gliomatosis: unusual MRI with non-enhancing nodular lesions on the cerebellar surface and spinal leptomeningeal enhancement. J Neurol Neurosurg Psychiatry 2000,69(3):385–8. 10.1136/jnnp.69.3.385
Kobayashi M, Hara K, Nakatsukasa M, Murase I, Toya S: Primary spinal leptomeningeal gliomatosis presenting visual disturbance as the initial symptom: case report. Acta Neurochir (Wien) 1996,138(4):480–481. 10.1007/BF01420313
Rights and permissions
About this article
Cite this article
Hansen, N., Wittig, A., Hense, J. et al. Long survival of primary diffuse leptomeningeal gliomatosis following radiotherapy and temozolomide: case report and literature review. Eur J Med Res 16, 415 (2011). https://doi.org/10.1186/2047-783X-16-9-415
- primary diffuse leptomeningeal gliomatosis
- radio-chemotherapy, malignant astrocytic cells, survival time