Spinal Relapse Research Articles

GCT-22. MEDICAL AND SURGICAL VARIABLES ASSOCIATED WITH RELAPSE IN CENTRAL NERVOUS SYSTEM (CNS) NONGERMINOMATOUS GERM CELL TUMORS (NGGCTS): SECONDARY ANALYSIS OF STRATUM 1 OF THE CHILDREN’S ONCOLOGY GROUP ACNS1123 PHASE 2 CLINICAL TRIAL

Abstract BACKGROUND ACNS1123 was a Phase 2 trial that evaluated the survival benefit of whole ventricular irradiation (WVI) instead of craniospinal irradiation in children with localized CNS NGGCTs who achieved a complete/partial radiographic response (CR/PR) to induction chemotherapy with negative tumor markers (beta-HCG/AFP) in serum and cerebrospinal fluid (CSF). Patients who did not achieve a CR/PR were considered inevaluable and removed from study therapy post-induction. METHODS In unplanned, exploratory analyses, we evaluated the association of age <15/>15-years at diagnosis, tumor location (pineal/suprasellar/bifocal/ventricular), tumor markers (beta-HCG/AFP) in serum and cerebrospinal fluid (CSF) at baseline (>/<1000), and rate of decline during induction in CR/PR and <CR/PR patients. Since most evaluable patients with relapse experienced distant failure in the spine, we assessed the impact of surgical variables, such as endoscopic third ventriculostomy (ETV)/biopsy/resection/combination, on spinal relapse in patients with or without disease progression. RESULTS 66 of 107 eligible patients achieved CR/PR with negative tumor markers while 41 patients did not. Bifocal tumors appeared to demonstrate a higher hazard for disease progression compared to suprasellar tumors (Hazard Ratio=5.4; p=0.0279). Otherwise, we did not find an association with progression-free-survival for any of the analyzed medical variables. Of 66 evaluable patients who received WVI, eight patients experienced relapse, with all patients demonstrating disease in the spine. No significant association was detected between any surgical variable (ETV/biopsy/resection) and spinal failure among evaluable patients who did or did not relapse; however, we had very limited power for these analyses due to very few events. CONCLUSION Current reliance on conventional parameters appears inadequate to identify biomarkers of response as well as relapse. Innovative approaches such as comprehensive genomic profiling of primary and recurrence tumor specimens could inform somatic clonal evolution and potential targeted therapies.

GCT-23. LONG-TERM FOLLOW-UP AND SURVIVALS OF PATIENTS WITH LOCALIZED CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS (NGGCT) ENROLLED ON ACNS1123: A CHILDREN’S ONCOLOGY GROUP (COG) STUDY

Abstract BACKGROUND ACNS1123 was a Phase 2 study to determine whether irradiation could be safely reduced without impacting survival in a subgroup of NGGCT patients. METHODS Patients with localized disease who achieved a complete (CR) or partial response (PR) to induction chemotherapy were eligible to receive reduced dose/volume of irradiation to 30.6Gy whole ventricular field with 54Gy tumor-bed boost. RESULTS 107 eligible NGGCT patients were accrued. The median age of patients at enrollment was 11 years (3.7-21.6). Eighty patients (75%) were male. Location was pineal in 58 (55%), suprasellar in 37 (35%), ventricles in 6 (6%), and bifocal in 6 patients (6%). Sixty-six (61.7%) patients achieved a CR/PR post-induction and were eligible and evaluable for the primary objective and received reduced dose and volume of irradiation. Eight patients progressed; 6 had a distant spinal relapse (outside the irradiation field) and 2 had a local plus distant relapse. As of December 31, 2023, the median follow-up time for eligible and evaluable patients was 5.6 years (0.9-7.9) from enrollment. Except for an unrelated death due to SARS-CoV-2 at 5.5 years from enrollment, there were no grade 3 or higher adverse events at the 60-month follow-up timepoint and no disease progressions beyond 2 years. The 5-year progression-free and overall survival for all eligible and evaluable patients are 87.9% (95% CI:79%-94.8%) and 92.4% (95% CI:82.8%- 96.8%), respectively. CONCLUSION Although the study was closed prematurely due to the concern of increased spinal relapse, the current data suggest that most patients with localized NGGCT and a CR/PR to chemotherapy will survive long-term, and, in fact, have similar survival (PFS and OS) to patients enrolled on ACNS0122 who received full dose craniospinal irradiation. The key to future biologic studies and clinical trials is identifying at diagnosis those patients at high risk for relapse.

IMMU-12. STANDARD OF CARE PLUS INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY (IMI) TO TREAT H3.3G34 DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND The prognosis of patients with H3.3G34 diffuse midline glioma is uniformly dismal. Since approval of IO-Vac® as advanced therapy medicinal product (27/05/2015), we treated two young patients with IMI in connection to the standard of care. METHODS BN (male 14y, diagnosis 01/2022) and JV (female 21y, diagnosis 12/2021) received partial resection resp. biopsy. Both underwent standard radiochemotherapy. RESULTS BN received 3/6 TMZ/Lomustin maintenance chemotherapy before start IMI. JV started with 1/12 TMZ courses together with IMI. Five-day immunogenic cell death (ICD) immunotherapy (Newcastle Disease Virus bolus injections and local modulated electrohyperthermia) were added to each maintenance chemotherapy block. After maintenance chemotherapy plus ICD immunotherapy, both received active-specific immunotherapy with two IO-Vac® vaccinations (autologous mature dendritic cells loaded with ICD-induced antigenic extracellular microvesicles). Both started with modulatory immunotherapy (4x ipilimumab/nivolumab q3w and further 6x nivolumab q4w) in combination with maintenance ICD immunotherapy. BN had a spinal relapse 19 months after initial diagnosis. He restarted with local radiotherapy and thereafter Lomustin plus Nivolumab, ultimately stopped due to arthritis. He died 24 months after diagnosis. Because of the observation of spreading disease, JV is now further treated with maintenance ICD immunotherapy using local modulated electrohyperthermia to the brain and to the upper and lower spine. She shows no evidence of progressive disease after >25 months. CONCLUSIONS The addition of IMI to standard of care for young patients with H3.3G34 diffuse midline glioma might give a glimpse of hope, and further anecdotal experiences should be collected. Additional treatment of the spinal axis with modulated electrohyperthermia might be required for patients with DMG.

LMIC-03. BRAINSTEM RADIATION NECROSIS IN A PATIENT WITH RECURRENT MEDULLOBLASTOMA. SUCCESFULL TREATMENT OF A HIGHLY FEARED COMPLICATION

Abstract BACKGROUND Medulloblastoma is the most common malignant brain tumor in pediatric population. Standard treatment combines surgery, risk-adapted craniospinal irradiation and chemotherapy. Given the well-known cognitive sequelae in young children associated to radiation, strategies in infants try to avoid upfront radiation. A significant number of patients treated during infancy will ultimately relapse. Re-irradition in relapse setting has proven to be effective in disease control (survival depending on several factors) although there is a concern in exceeding radiation tolerance and risk of toxicity. METHODS Herein, we describe the case of male patient that presented at 1 year of age with a non-metastatic anaplastic medulloblastoma that was completely resected. He received 3 cycles of adjuvant chemotherapy (as per Head Start II), local relapse was detected in tumor bed during evaluation and was completely resected, afterwards he received myeloablative chemotherapy with stem cell rescue and posterior fossa radiation therapy (54 Gy). At 8 months off therapy patient developed spinal relapse in imaging with negative cytology, then treated with spinal irradiation 36Gy without adjuvant chemotherapy. He remained disease free during 12 months, then tumor recur at the right cerebellopontine angle, surgery was complete and there was no evidence of distant disease. Patient received adjuvant local radiation with 30.6Gy followed by chemotherapy (bi weekly bevacizumab + irinotecan). Cumulative maximal dose to brainstem was 84Gy. 2 months after radiation patient presented with extreme sleepiness and imaging findings compatible with brainstem radiation necrosis, symptoms resolved promptly after scheduled bevacizumab. Patient is currently 6-year-old and remains free of disease after 3 years off therapy. CONCLUSION Medulloblastoma treatment in infants is challenging because survival is not the only goal. Future clinical trials will help to better tailored treatment based on molecular biology. Re-irradiation in medulloblastoma has been described as well tolerated but clinician should be aware of its complications and management.

Excluding prepontine cistern from whole ventricle radiotherapy target volume in localized germinoma.

The target delineation of whole ventricle radiotherapy (WVRT) in germinoma varies among radiation oncologists, especially regarding the inclusion of the prepontine cistern (PC). We evaluated the outcome of PC-sparing WVRT in localized germinoma. We identified 87 localized intracranial germinoma patients who received radiotherapy (RT) following chemotherapy between 1999 and 2020. By institutional policy, RT for localized germinoma excluded PC from the target volume. WVRT was delivered to 65 patients (74.7%) and involved field radiotherapy (IFRT) to 22 patients (25.3%). The median dose was 45.0 Gy (range, 23.4 to 55.8 Gy) for the primary tumor and 19.8 Gy (rangem 14.4 to 36.0 Gy) for the whole ventricle. We analyzed the dosimetric differences of the organs at risk between the PC-excluding plans and the PC-including ones. The median follow-up duration was 7.8 years (range, 1.0 to 22.5 years). The 10-year recurrence-free survival and overall survival rates were 86.3% and 90.9%, respectively. The recurrences occurred in eight patients (8.7%), including five patients after IFRT and three after WVRT. Five of them showed recurrences at lateral ventricles and only one patient experienced spinal cord relapse. However, no relapse in the PC occurred. Endoscopic third ventriculostomy was not a significant prognostic factor. The dosimetric comparisons showed significantly lower mean doses to the brainstem and the cochleae when the PC was excluded. WVRT for localized germinoma can safely exclude the PC in the target volume, reducing radiation dose to the brain stem. The target protocol needs to reach a consensus regarding the PC in prospective trials.

A Phase 2 Trial of Response-Based Radiation Therapy for Localized Central Nervous System Germ Cell Tumors: Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors

Children's Oncology Group study ACNS1123 tested the efficacy of reduced dose and field of radiation therapy (RT) for patients with localized nongerminomatous germ cell tumors (NGGCT) who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for patients eligible for reduced RT in this phase 2 trial. Patients with localized NGGCT with CR/PR after induction chemotherapy received reduced RT to 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed total dose. An atlas was provided to assist with complex RT volumes. Early interventional review was performed for the initial RT plan. Complete RT plans for all patients and images of relapsed patients were centrally reviewed at completion of therapy. Between May 2012 and September 2016, 107 eligible patients were enrolled and 66 achieved a CR/PR after induction chemotherapy (± second-look surgery) and were eligible for reduced RT. Median follow-up was 4.4 years. Median age was 11.0 years (3.7-21.6), and 75% were male. Progression-free survival and overall survival at 4 years were 87.9% ± 4.0% and 92.4% ± 3.3% for 66 evaluable patients, respectively. Eight patients relapsed: 6 with isolated spinal relapse and 2 with disease in the brain and spine. After central review, 62 (94%) patients had RT targets contoured and dose delivered per protocol. None of the patients with deviations (n=4) have progressed. Patterns of failure suggest the spine is at risk for recurrence for patients with localized NGGCT who receive reduced RT after a CR/PR to induction chemotherapy. Although survival data are encouraging, the pattern of failure has influenced the next prospective trial design. RT compliance was excellent despite complexity of radiation volumes, suggesting that providing visual guidance in the form of an online atlas contributes to higher quality RT plans.

Updated Experience of Mycobacterium chimaera Infection: Diagnosis and Management in a Tertiary Care Center.

BackgroundDespite safety communications from the Food and Drug Administration (FDA) regarding the outbreak of Mycobacterium chimaera infections (MCIs) from contaminated heater-cooler devices, new cases continue to be identified.MethodsWe retrospectively reviewed confirmed cases of MCI that were managed at Mayo Clinic sites (Arizona, Florida, and Minnesota) from 09/2015 to 01/2021. Clinical histories including prior cardiovascular surgery were recorded. Diagnostic workup including ophthalmologic examination, imaging, and laboratory testing was reviewed. Treatment and survival outcomes on follow-up were obtained.ResultsTwelve patients with MCI were included. All patients had aortic valve or graft replacement. Five patients had their surgical procedures following the 10/15/2015 FDA safety communication. The mean time from surgery to symptom onset (range) was 32 (13–73) months. Ten of 11 patients who underwent ophthalmologic examination had chorioretinal abnormalities. Three patients who underwent microbial cell-free deoxyribonucleic acid sequencing tested positive for M. chimaera, which was subsequently confirmed with blood culture growth. Echocardiography and positron emission tomography/computed tomography (PET/CT) revealed evidence of prosthetic valve/graft infection in 7/12 (58.3%) and 6/10 (60.0%) of cases, respectively. Seven patients (58.3%) underwent redo cardiovascular surgery. Of these, 1 patient died 2 days postdischarge, 1 experienced spinal osteomyelitis relapse, and another had interval prosthetic valve fluorodeoxyglucose (FDG) uptake on PET/CT suspicious for recurrent infection. Among 4 patients on medical therapy only, 3 expired or transitioned to hospice during follow-up.ConclusionsMCI continues to occur despite the FDA communications. Incorporation of ophthalmologic examination and use of advanced tools may improve MCI diagnosis. The mortality in these patients is high even with aggressive surgical/medical management.

Impact of previous disease-modifying treatment on effectiveness and safety outcomes, among patients with multiple sclerosis treated with alemtuzumab

ObjectivesAlemtuzumab is effective in patients with active multiple sclerosis but has a complex safety profile, including the development of secondary autoimmunity. Most of patients enrolled in randomised clinical trials with...

GCT-42. CLINICAL CHARACTERISTICS OF LOCALIZED CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS (NGGCT) PATIENTS ENROLLED ON ACNS1123 WITH RELAPSE: A CHILDREN’S ONCOLOGY GROUP (COG) STUDY

ACNS1123 was a Children’s Oncology Group Phase 2 study that was undertaken to determine whether irradiation could be safely reduced without impacting survival in a subgroup of NGGCT patients. Between May 2012-Jan 2017, 107 eligible patients were accrued to Stratum 1 (NGGCT stratum). Sixty-six (61.7%) patients achieved a complete/partial response (CR/PR) to induction chemotherapy and received 30.6Gy whole ventricular field irradiation followed by 54Gy tumor-bed boost achieving a 2-year progression-free survival rate of 89% (95% CI:81%-97%) and overall survival rate of 92% (95% CI:86%- 99%). Eight patients progressed; 6 had a spinal relapse and 2 patients had a local plus spinal relapse. Seven of eight patients had marker elevation at relapse and data was not available in one patient. At diagnosis, location was pineal in six cases, suprasellar in one, and bifocal in one case. Four patients had beta HCGβ and AFP elevation and two each had HCGβ and AFP elevation alone at diagnosis. Only two patients had HCGβ or AFP >1000 (HCGβ 3550 in one patient and AFP of 1340 in another). All eight patients were CR by markers; four had radiographic CR and four had a PR. Five patients had surgery at diagnosis: two had embryonal carcinoma, one germinoma, and two mixed germ cell tumor with malignant elements on histology. A consistent significant risk factor could not be identified to explain excess of spinal failures seen in our cohort.

Posterior Percutaneous Endoscopic Cervical Diskectomy as a treatment for cervical radiculopathy

Anterior cervical diskectomy and fusion (ACDF) is the gold standard treatment for patients with cervical radiculopathy. However, the use of ACDF for patients with cervical radiculopathy can result in several disadvantages, such as limitation of motion and accelerating degeneration of adjacent segment. An alternative, less invasive endoscopic technique, posterior percutaneous endoscopic cervical diskectomy (PPECD), was applied to address the above problems associated with ACDF. The patient presented with pain and weakness of the left arm for 2 years. P-PECD was applied and complete decompression of the nerve root was achieved. The symptoms were relieved after surgery. Postoperative MR showed the ruptured disk fragment was successful removed. No spinal instability or symptom relapse was observed in follow-up. PPECD may be an option for patients with cervical radiculopathy.

Loss of Heterozygosity and Possible Loss of Allele Amplification in Homozygous Short Tandem Repeats Loci in Two ALL Patients with Central Nervous System and Bone Marrow Relapses

Introduction: Loss of heterozygosity (LOH) was described for many forms of cancer including leukemia. LOH may contribute to oncogenesis through the deletion of tumor suppressor genes due to appropriate allelic loss. LOH in short tandem repeats loci (STR) has been reported for solid tumors and is widely used as malignant cells population marker. It should be noted that little is known yet about possible loss of one of certain homozygous alleles in tumour cells and STR analysis might be a promising approach to investigate this phenomenon. STR analysis is used as a routine test for chimerism monitoring after bone marrow transplantation. It could not also be excluded that recipient's chimerism estimation may be distorted in some cases due to LOH issues.The aim: To investigate possible allele loss in homozygous loci in tumour cells and to assess the contribution of LOH to the error in mixed chimerism estimation.Patients and Methods: This study includes analysis of STR DNA-profiles of two ALL patients after allogeneic stem cells transplantation. Patient 1 was 54 years old female with B-ALL, she underwent allogenic BM transplantation but after it she had four central nervous system (CNS) relapses and three bone marrow relapses. Patient 2 was 23 years old male with preT-ALL, two CNS relapses: first before transplantation and second after it. The DNAs were isolated from bone marrow samples of patients in remission before transplantation, from donors blood samples, from cerebrospinal fluid during neuro relapse and from bone marrow samples. The presence of blast cells in bone marrow samples and cerebrospinal fluid was confirmed morphologically and cytogenetically. STR-profiles were assessed by polymerase chain reaction with COrDIS Plus multiplex kit for amplification of 19 polymorphic STR-markers and amelogenin loci (Gordiz Ltd, Russia). The fragment analysis was performed on ABI3130 Genetic Analyzer. The data processing was accomplished using GeneMapper v.4-0 software.Results: The STR profile analysis for Patient 1 showed complete recipient chimerism in cerebrospinal fluid with LOH in 10 from 15 heterozygous loci (Fig.1a,b) comparative to control sample of DNA (bone marrow before transplantation). The same LOH pattern was detected in archival DNA sample from first spinal relapse. Mixed chimerism in bone marrow samples estimated by STR analysis was equal to blast cell percentage assessed by cytogenetics. Loss of non-informative allele in D16S539 (Fig.1b) didn't distort chimerism estimation. However decreased levels of mixed chimerism were calculated in two homozygous loci (Fig.1a,c). We suspected that this decrease could be caused by the loss of one allele amplification in homozygous locus. Therefore, we proposed the mathematical model f(x), where x - is donor percentage in chimera, f(x) - difference between real recipient percentage (100-x) and calculated for locus with loss of allele amplification ((100-x)/2:((100-x)/2+x))*100% (Fig.1c) to test this hypothesis. The highest difference in chimerism calculation (about 17%) is expected in about 40% of donor and 60% recipient percentage. For Patient 2 the STR analysis detected only one LOH locus in DNA samples from cerebrospinal fluid during CNS relapse before and after BMT. However this patient has eight homozygous STR loci and complete donor chimerism in bone marrow. To find possible “loss of allele amplification” we used the artificial chimera, the mix of Patient 2 and unrelated random healthy donor DNA (Fig.1d). We used control DNA of Patient 2 (bone marrow before BMT) to check chimerism level deviations in loci of interest. The decreased level of mixed chimerism was detected in two homozygous loci from cerebrospinal fluid DNA-sample. The decreased estimate for chimerism correlated with proposed math model. For the same STR loci in control DNA no chimerism deviations were detected in mixed artificial chimera (Fig.1e).Conclusions: The LOH loci pattern might be preserved during long period of disease for certain malignant clone. Mixed chimerism or artificial mixed chimera can be useful in finding of homozygous loci with loss of one allele amplification. We suppose homozygous loci are the preferable subject for investigating LOH mechanisms. Loci with “loss of allele amplification” might be the used as malignant cells population marker.This study was supported by the Russian Foundation for Basic Research (RFBR) grant 18-015-00399a. DisclosuresRisinskaya:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Chabaeva:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Kulikov:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding.

Is there an increased risk of spinal relapse in standard-risk medulloblastoma/primitive neuroectodermal tumor patients who receive only a reduced dose of craniospinal radiotherapy?

Medulloblastoma (MBL) is the most common pediatric brain malignancy. Postoperative radiotherapy to the entire craniospinal axis is the standard-of-care but has linked to long-term morbidity. In this study, we analyzed the implication of reduced dose craniospinal radiotherapy (RT) for survival and pattern of relapse in MBL patients. The clinical characteristics of 32 consecutively diagnosed medulloblastoma/primitive neuroectodermal tumor patients were analyzed. After surgical resection, a dose of 23.4Gy of spinal RT with a posterior fossa boost of 30.6Gy was prescribed to standard-risk patients, whereas high-risk patients received 36Gy spinal RT with additional boosts to the posterior fossa up to 54Gy. Then, both groups received the same chemotherapy protocol. Five-year OS for standard and high-risk patients was 94 and 50%, respectively. When analyzing prognostic factors, postoperative tumor size is the most important one which affects the OS. Ten patients relapsed during follow-up, and there was no isolated spinal relapse in either group. The risk of isolated spinal relapse does not increase with reduced-dose craniospinal RT, since there is no isolated relapse in either the standard or high-risk groups of patients.

Interest of [18F]fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of relapse in patients with spinal infection: a prospective study

Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [18F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for ≥12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [18F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI.

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network.

Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy. The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months. Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis. In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.

Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI

Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97% of all relapses occurred in the brain and 3% were isolated to the spine. Relapse was identified in 226 (8%) brain and 48 (4%) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

Spinal hydatidosis relapse: a case report.

Human cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the Echinococcus granulosus and the most common sites affected are the liver and lung in approximately 80–90% of cases. The hydatid bone represents the 0.5–2.5% of all cases and localization cord is present about 50% of the time. This benign and commonly asymptomatic disease may simulate an aggressive malignancy because of osseous destruction and aggressive extension. We report a case of a 42-year-old male patient, presented with an unusual spinal hydatidosis relapse, related to anthelmintic drug therapy withdrawal after 10-year treatment. The man had previous excision of chest and hepatic hydatid cysts (resp., 10 and 3 years ago) and after primary mediastinal and spinal involvement (3 years ago) he was lost to follow-up and discontinued drug therapy. The patient underwent surgery and the postoperative histopathology confirmed the diagnosis. The patient recovered with no complications. Despite significant progress in diagnostic imaging, pharmacological and surgical therapy, spinal CE remains associated with high morbidity.

Relapse patterns in pediatric embryonal central nervous system tumors

Embryonal tumors of the central nervous system (CNS) share histological features and were therefore initially grouped as primitive neuroectodermal tumors (PNET) and treated similarly. We sought to determine the relapse patterns of specific embryonal CNS tumors. We conducted a historical cohort study of children diagnosed with CNS embryonal tumors from January 2000 to December 2011 in two pediatric neuro-oncology centers. Patients of 21 years of age or younger at time of presentation with a diagnosis of medulloblastoma, supratentorial PNET, pineoblastoma or atypical teratoid/rhabdoid tumor (ATRT) and at least one surveillance MRI were included. A total of 133 patients met inclusion criteria and 49 (37 %) patients relapsed during the observation period. The majority (79 %) of sPNET relapses were local, whereas all (100 %) PB relapses were associated with diffuse leptomeningeal disease. Relapse patterns for MB were more diverse with local recurrence in 27 %, distant recurrence in 35 % and diffuse leptomeningeal disease in 38 %. The frequency of relapses involving the spine differed (p < 0.001) between tumor types (MB 28/55 [51 %], sPNET 3/33 [9 %], ATRT 3/7 [43 %] and PB 12/12 [100 %]). No sPNET patients had isolated spinal relapse (0/14). Embryonal tumors were found to have divergent patterns of recurrence. While medulloblastoma has variable relapse presentations, sPNET relapses locally and pineoblastoma recurs with diffuse leptomeningeal disease involving the spine. These results point toward possibly new upfront treatment stratification among embryonal tumors in accordance with relapse pattern.

Unusual Symptoms and Syndromes in Multiple Sclerosis

In multiple sclerosis (MS), symptoms vary widely from patient to patient. Certain events in MS are well recognized (eg, optic neuritis, brainstem and spinal cord relapses) and do not lead to much clinical confusion. However, other events that occur in MS may be less expected and may be underrecognized by some clinicians and may lead to an extensive and potentially unnecessary investigation for what is a known problem in MS. This article reviews Lhermitte sign, Pulfrich phenomenon, Uhthoff phenomenon, and the useless hand of Oppenheim, along with the underrecognized phenomena of transient neurologic events (including tonic spasms). Disorders of temperature regulation in MS (likely based on hypothalamic involvement) which can present with bizarre behavioral change and evade diagnosis, are also discussed. The article concludes with a review of epilepsy and sleep disorders in MS, both of which appear to occur at an increased frequency in the MS population and may have implications for therapy. This article is meant to help clinicians recognize and treat this fascinating set of underrecognized phenomena in MS and perhaps save patients trips to the emergency department, extraneous testing, and ineffective intervention.

Spinal hydatidosis relapse related to albendazole withdrawal after 20-year treatment

Spinal hydatidosis relapse related to albendazole withdrawal after 20-year treatment

A comparative study of CSF neurofilament light and heavy chain protein in MS

Background: There is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)). Methods: We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light® enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfHSMI35 assay. Results: Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls (p ≤ 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease (rs = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfHSMI35 in both CIS patients (p = 0.001) and all MS stages grouped together (p = 0.035). Conclusions: NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light® ELISA performed better in discriminating patients from controls, compared with the ECL-NfHSMI35 immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.