Anesthesia Exposure during Therapy Predicts Neurocognitive Outcomes in Survivors of Childhood Medulloblastoma.

OBJECTIVE: To examine the contribution of anesthesia exposure during treatment for childhood medulloblastoma to neurocognitive outcomes 3 years after tumor diagnosis. STUDY DESIGN: In this retrospective study, anesthesia data were abstracted from medical records for 111 patients treated with risk-adapted protocol therapy at St Jude Children's Research Hospital. Neurocognitive testing data were obtained for 90.9% of patients. RESULTS: For the 101 patients (62.4% male) who completed testing, mean age at diagnosis was 10.1 years, and 74.3% were staged to have average-risk disease. Anesthesia exposure during treatment ranged from 1 to 52 events (mean = 19.9); mean cumulative duration per patient was 21.1 hours (range 0.7-59.7). Compared with normative expectations (16%), the group had a significantly greater frequency of at-risk scores (<1 SD) on measures of intelligence (28.7%), attention (35.2%), working memory (26.6%), processing speed (46.7%), and reading (25.8%). Including anesthesia exposure duration to linear regression models accounting for age at diagnosis, treatment intensity, and baseline IQ significantly increased the predicted variance for intelligence (r2 = 0.59), attention (r2 = 0.29), working memory (r2 = 0.31), processing speed (r2 = 0.44), and reading (r2 = 0.25; all P values <.001). CONCLUSIONS: In survivors of childhood medulloblastoma, a neurodevelopmentally vulnerable population, greater exposure to anesthesia significantly and independently predicts deficits in neurocognitive and academic functioning. When feasible, anesthesia exposure during treatment should be reduced.

Cytogenetic findings in pediatric radiation-induced atypical meningioma after treatment of medulloblastoma: case report and review of the literature.

Ionizing radiation is the most recognized risk factor for meningioma in pediatric long-term cancer survivors. Information in this rare setting is exceptional. We report the clinical and cytogenetic findings in a radiation-induced atypical meningioma following treatment for desmoplastic medulloblastoma in a child. This is the second study to describe the cytogenetic aspects on radiation-induced meningiomas in children. Chromosome banding analysis revealed a 46, XX, t(1;3)(p22;q12), del(1)(p?)[8]/46, XX[12]. Loss of chromosome 1p as a consequence of irradiation has been proposed to be more important in the development of secondary meningiomas in adults. Deletions in the short arm of chromosome 1 also appear to be a shared feature in both pediatric cases so far analyzed.

Early traits of metabolic syndrome in pediatric post-cancer survivors: outcomes in adolescents and young adults treated for childhood medulloblastoma / Fatores precoces para síndrome metabólica em sobreviventes de câncer pediátrico: resultados em adolescentes e adultos jovens tratados por meduloblastoma na infância

OBJECTIVE: To analyze traits of metabolic syndrome (MetS) in medulloblastoma survivors. SUBJECTS AND METHODS: Sixteen childhood medulloblastoma survivors aged 18.0 (4.4) years, with history of craniospinal radiation therapy (RT) were compared with nine control subjects matched by age, gender, and body mass index, according to fat distribution, metabolic and cardiovascular variables. RESULTS: Medulloblastoma patients showed increases in waist circum-ference and its relationships (all p < 0.05), and HOMA1-IR (p = 0.006), which were modified by growth hormone (GH) secretion status. However, these increases were within normal range. CONCLUSIONS: Adolescent and young adult survivors of medulloblastoma showed centripetal fat deposition and decreased insulin sensitivity, associated with GH status. Pediatric brain tumor survivors following RT should be monitored for the diagnosis of MetS traits predisposing to cardiovascular disease.

OBJETIVO: Analisar características que predispõem para síndrome metabólica (SM) em sobreviventes de meduloblastoma. SUJEITOS E MÉTODOS: Dezesseis sobreviventes de meduloblastoma pediátrico, 18,0 (4,4) anos, história de radioterapia (RT) cranioespinhal, comparados a nove controles pareados por idade, sexo e índice de massa corporal, de acordo com distribuição de gordura, variáveis metabólicas e cardiovasculares. RESULTADOS: Pacientes com meduloblastoma mostraram aumento da cintura e relações (todos p < 0,05) e HOMA1-IR (p = 0,006), modificados pela secreção do hormônio de crescimento (GH), mas dentro dos limites de normalidade. CONCLUSÕES: Sobreviventes adolescentes e adultos jovens de meduloblastoma apresentaram deposição centrípeta de gordura e diminuição da sensibilidade à insulina, associados ao estado do GH. Sobreviventes de tumor cerebral pediátrico que receberam RT devem ser monitorados para diagnosticar fatores para SM predispondo à doença cardiovascular.

Intellectual impairment after treatment for medulloblastoma and astrocytoma in childhood: the Brazilian experience.

BACKGROUND: This study investigated the impact of posterior fossa tumors and their respective treatments, and the impact of clinical and sociodemographic variables, on the intelligence quotient (IQ) of Brazilian children. METHODS: Twenty patients took part in the study, of which 13 were diagnosed with astrocytoma (average age at evaluation 10.2 y) and 7 with medulloblastoma (average age at evaluation 9.2 y). The first subgroup was submitted exclusively to tumor resection surgery and the second subgroup underwent surgery, chemotherapy (Vincristine, Cisplatine, and Carmustine), and radiotherapy (total dose of 54 Gy). The Wechsler Intelligence Scale for Children (WISCIII) was used. RESULTS: The following statistically significant effects were identified: treatment modality on performance intelligence quotient scores (P=0.02) and processing speed index (PSI) (P=0.01); presence of hydrocephalus at diagnosis on verbal intelligence quotient (P=0.04); tumor localization on perceptual organization index (P=0.03); time interval between diagnosis and neuropsychological evaluation on PSI (P=0.05) and freedom from distraction index (P=0.03); and level of parental formal education on full scale IQ (P=0.02). CONCLUSIONS: Exposure to radiotherapy has a significant effect on processing speed and consequently on global intellectual capacity. The impact on intelligence of clinical and sociodemographic variables such as tumor localization, time interval between diagnosis and cognitive evaluation, and parental level of formal education is confirmed in the specific setting of a developing country.

Early traits of metabolic syndrome in pediatric post-cancer survivors: outcomes in adolescents and young adults treated for childhood medulloblastoma.

OBJECTIVE: To analyze traits of metabolic syndrome (MetS) in medulloblastoma survivors. SUBJECTS AND METHODS: Sixteen childhood medulloblastoma survivors aged 18.0 (4.4) years, with history of craniospinal radiation therapy (RT) were compared with nine control subjects matched by age, gender, and body mass index, according to fat distribution, metabolic and cardiovascular variables. RESULTS: Medulloblastoma patients showed increases in waist circumference and its relationships (all p < 0.05), and HOMA1-IR (p = 0.006), which were modified by growth hormone (GH) secretion status. However, these increases were within normal range. CONCLUSIONS: Adolescent and young adult survivors of medulloblastoma showed centripetal fat deposition and decreased insulin sensitivity, associated with GH status. Pediatric brain tumor survivors following RT should be monitored for the diagnosis of MetS traits predisposing to cardiovascular disease.

Inhibin B and anti-Müllerian hormone as markers of gonadal function after treatment for medulloblastoma or posterior fossa ependymoma during childhood.

OBJECTIVE: To evaluate the roles of hypothalamic-pituitary and spinal irradiations and chemotherapy in gonadal deficiency after treatment for medulloblastoma or posterior fossa ependymoma by measuring levels of plasma inhibin B and antimüllerian hormone (AMH). STUDY DESIGN: A total of 34 boys and 22 girls were classified as having normal levels of plasma follicle-stimulating hormone (FSH; <9 IU/L), or abnormal levels of FSH (>9 IU/L) and luteinizing hormone (LH; <5 or >5 IUL). RESULTS: Two boys had partial gonadotropin deficiency, combined with testicular deficiency in one boy. Six boys had increased levels of FSH, indicating tubular deficiency, combined with Leydig cell deficiency in 5 boys. The 7 boys with inhibin B levels <100 ng/mL included the one with combined deficiencies and the 6 with testicular deficiency. Puberty did not progress in 7 girls; 3 had gonadotropin deficiency, combined with ovarian deficiency in one, and 4 had increased FSH levels, indicating ovarian deficiency. Inhibin B and AMH levels were low in the girl with combined deficiencies, in the 4 girls with ovarian deficiency, and in 4 girls with normal clinical-biological ovarian function, including 2 who underwent ovarian transposition before irradiation. CONCLUSION: The plasma concentrations of inhibin B and AMH are useful means of detecting primary gonad deficiency in patients with no increase in their plasma gonadotropin levels because of radiation-induced gonadotropin deficiency.

Evaluación de la talla final y sobrevida libre de eventos en pacientes sobrevivientes de meduloblastoma con deficiencia de hormona de crecimiento, tratados o no con hormona de crecimiento biosintética recombinante humana en la niñez. Comparación con pacientes con craneofaringioma tratados con rhGH / Evaluation of final height and event-free survival in medulloblastoma patients with growth hormone deficiency with and without biosynthetic recombinant human growth hormone treatment in childhood

Introduccion: La deficiencia de GH (DGH) y la radioterapia espinal (RE) han sido implicadas en la etiología de la talla adulta (TA) baja en los sobrevivientes de meduloblastoma en la niñez. Sin embargo la dinámica del crecimiento luego del diagnóstico tumoral y la efectividad de la Hormona de crecimiento biosintética recombinante humana (rhGH) sobre la TA en comparación con sobrevivientes no tratados con rhGH no han sido reportadas. Objetivo. Evaluación de la talla (T) SDS (SDST) desde el diagnóstico del meduloblastoma y el efecto de la rhGH en pacientes con DGH comparando con pacientes no tratados con rhGH y con pacientes con craniofaringioma y DGH, tratados con rhGH. Analizar si había alguna diferencia en la sobrevida libre de eventos en los pacientes con meduloblastoma al ser tratados con rhGH. Material Clínico y Métodos. Catorce pacientes con meduloblastoma recibieron rhGH hasta la TA, grupo meduloblastoma tratado con GH (GrMGH). Diecinueve pacientes rechazaron la terapia con rhGH, grupo meduloblastoma control (GrMC). Se midieron la talla parada (T) y la talla sentada (Tsent). Ocho pacientes con craneofaringioma recibieron rhGH hasta la TA (GrCra). Se realizó seguimiento de 72 pacientes con meduloblastoma, 20 con tratamiento con rhGH. Resultados. En GrMGH, la media±DS SDST disminuyó de 0.09±0.63 al diagnóstico del tumor a -1.38±0.91 al diagnóstico del DGH, y a -1.90±0.72 al comienzo de rhGH, p<0.01, pero se mantuvo sin cambios durante el tratamiento con rhGH (TA -2.12±0.55). En GrMC la SDST (-0.25±0.88) no fue diferente de GrMGH al diagnóstico del tumor, pero fue -3.40±0.88 a la TA, significativamente menor que en GrMGH, p=0.001. La Tsent SDS a la TA (-4.56±0.82) fue significativamente menor que al comienzo de rhGH (-2.86±0.75), p=0.003, y no fue diferente de GrMC (-4.85±1.77). El GrCra mostró la mayor ganancia de talla (GT = TA-SDSTinicial), p< 0.007, y la menor pérdida de talla (PT= Tblanco - TA), p < 0.0001. Conclusión. El tratamiento con rhGH mejora la TA en sobrevivientes de meduloblastoma en la niñez con DGH, pero no el crecimiento espinal. Las características del crecimiento y la respuesta a rhGH son diferentes en GrMGH y en GrCra, mientras que el primer grupo sólo pudo mantener la talla relativa, el segundo mostró una franca recuperación del crecimiento. Además no hubo diferencias en la sobrevida libre de eventos en los pacientes con meduloblastoma con y sin tratamiento con rhGH (AU)

Background. GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of (rhGH) Recombinant human Growth Hormone on AH in comparison with rhGH-untreated survivors has not been reported. Aim. Follow up of height (H) SDS (HSDS) after diagnosis of meduloblastoma, and the effect of rhGH in GHD meduloblastoma patients. Comparison with GH-untreated GHD meduloblastoma patients and with GHD craniopharyngioma patients treated with rhGH. To evaluate event free survival in medulloblastoma patiens treated with rhGH. Clinical Material and Methods. Fourteen survivors of medulloblastoma received rhGH treatment until AH, Medulloblastoma GH-treated group (MGHGr). Nineteen patients refused rhGH therapy, GH-untreated Control Medulloblastoma Group, (MCGr). Standing H and sitting H (SitH) were measured. Eight patients with craniopharyngioma received rhGH treatment until AH (CraGr). 72 patients with medulloblastoma were followed up, 20 with rhGH. Results. In MGHGr, mean±SD HSDS decreased from 0.09±0.63 at tumor diagnosis to -1.38±0.91 at diagnosis of GHD, and to -1.90±0.72 at the onset of rhGH, p<0.01, but it remained unchanged during rhGH (AH -2.12±0.55). MCGr HSDS (- 0.25±0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 ± 0.88 at AH, significantly lower than in MGHGr, p=0.001. SitH SDS at AH (-4.56±0.82) was significantly lower than at the onset of rhGH (-2.86±0.75), p=0.003, and it was not different from MCGr (-4.85 ± 1.77). CraGr showed the highest height SDS gain (HG = FH ­ startHSDS), p<0.007, and the lowest height lost (HL = targetH - AH), p< 0.0001. Conclusions. rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth. Growth pattern and response to rhGH differed in MGHGr and CraGR, while the former just could maintain height SDS under treatment, the latter showed a clear catch up growth. There wasn't any difference in the event free survival in medulloblastoma patients with or without rhGH (AU)

Effectiveness of rhGH treatment on adult height in GH-deficient childhood survivors of medulloblastoma.

BACKGROUND: GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of rhGH on AH in comparison with rhGH-untreated survivors have not been reported. AIM: To follow height (H) SDS (HSDS) since tumor diagnosis and the effect of rhGH in GHD patients, comparing with GH-untreated GHD patients. METHODS: 14 patients received rhGH treatment until AH (medulloblastoma GH-treated group, MGHGr). 19 patients refused rhGH therapy (GH-untreated control medulloblastoma group, MCGr). Standing H and sitting H (SitH) were measured. RESULTS: In MGHGr, mean +/- SD HSDS decreased from 0.09 +/- 0.63 at tumor diagnosis to -1.38 +/- 0.91 at diagnosis of GHD, and to -1.90 +/- 0.72 at the onset of rhGH, p < 0.01, but it remained unchanged during rhGH (AH -2.12 +/- 0.55). MCGr HSDS (-0.25 +/- 0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 +/- 0.88 at AH, significantly lower than in MGHGr, p = 0.001. SitH SDS at AH (-4.56 +/- 0.82) was significantly lower than at the onset of rhGH (-2.86 +/- 0.75), p = 0.003, and it was not different from MCGr (-4.85 +/- 1.77). CONCLUSIONS: rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth.

Speech-language and hearing complaints of children and adolescents with brain tumors.

Central nervous system (CNS) tumors generally leave sequelae that may compromise speech, language, swallowing, hearing, and voice functions. This report describes the incidence of speech-language and hearing complaints and disorders in children and adolescents with CNS tumor under treatment at one of the most important Brazilian reference center for pediatric cancer. One-hundred ninety patients were examined for speech-pathology screening and analysis: forty-two percent presented with complaints and symptoms. From the remaining patients, 68% presented clinical symptoms and 32% were actually free from any speech-language and hearing-related symptoms. The high incidence of complaints and symptoms indicate that these patients might benefit from specific rehabilitation interventions.

Mutismo cerebeloso luego de la resección de tumores de fosa posterior. Presentación de dos casos / Cerebellar mutism after posterior fossa tumor resection. Report of 2 cases

El mutismo cerebeloso es un síndrome complejo e infrecuente que se asocia con la resección de tumores de fosa posterior. Con el perfeccionamiento de las técnicas diagnósticas, funciones cognitivas y del lenguaje han sido atribuidas al cerebelo. Presentamos dos casos de cinco y ocho años respectivamente, que desarrollaron mutismo luego de la exéresis de un meduloblastoma y un astrocitoma pilocítico. El sustrato anatómico del mutismo y sus probables etiologías son analizadas en este trabajo (AU)

Hemorragia intratumoral en un meduloblastoma de cerebelo como complicación posterior a la derivación ventriculoperitoneal: presentación de un caso clínico / Intratumoral hemorrhage in a cerebellar medulloblastoma as a complication after ventriculoperitoneal shunting: report of a case

Se describe el caso de un niño de 9 años de edad a quien se le diagnostica por tomografía computada un voluminoso proceso expansivo de fosa posterior, de línea media, con una importante dilatación ventricular supratentorial, decidiéndose tratar en una primera instancia la hidrocefalia, mediante la colocación de un sistema de derivación ventrículo peritoneal. Presentó como complicación en posoperatorio una hemorragia intratumoral, y a pesar de que se abordó la fosa posterior de emergencia el paciente falleció. Se analizaron casos similares descritos en la literatura y se discute la conducta a seguir en pacientes con esta patología (AU)

[Neurophysiology of pain in tentorial irritation: description of a case secondary to medulloblastoma]. / Neurofisiologia álgica na irritação tentorial. Descrição de um caso secundário a meduloblastoma.

We report the case of a 32-year-old woman who complained of dull and compressing occipital pain, with unilateral radiation to the left frontal and supraorbital areas (of the sickening type). The radiological, clinical, neurosurgical and neuropathologic investigation disclosed a medulloblastoma bulging and tickening the tentorium cerebelli. This case shows how mechanical stimuli of the structures innervated by the tentorial nerve can cause pain with characteristics of trigeminal and cervical involvement.

Neurofisiologia álgica na irritaçäo tentorial: descriçäo de um caso secundário a meduloblastoma / Neurophysiology of pain in tentorial irritation: description of a case secondary to a medulloblastoma

Relatamos o caso de paciente do sexo feminino, com 32 anos de idade, com sintomas álgicos na regiao occipital, compressivos de forte intensidade e com irradiaçao frontal, supraorbitária e orbitária esquerda, relacionada a movimentos de flexao e extensao do pescoço, com característica lancinante e duraçao de até 9 segundos. A investigaçao radiológica, clínica, neurocirúrgica e neuropatológica evidenciou um meduloblastoma que aderia à membrana tentorial promovendo espessamento e compressao das estruturas venosas desta regiao. Atribuímos ao estímulo mecânico sobre estas estruturas vasculares tentoriais as manifestaçoes álgicas envolvendo as conexoes entre o trigêmeo e os primeiros segmentos medulares cervicais.

Preoperative and postoperative analysis of visual and auditory memory in children with cerebellar tumors.

Motivated by the extensive clinical and experimental evidence that links the cerebellum to cognitive processes, we analyzed the auditory and visual memory of nine children with cerebellar tumors. Five patients had midline lesions and four had cerebellar hemispheric tumors. The patients were tested before and after surgery. One of the patients was also tested at 4 and 24 months after surgery. A third group constituted by four children, siblings of some of the patients, served as control. Statistically significant differences (P < 0.05) were found in the test of auditory memory, in which children with cerebellar tumors made a higher number of errors than their normal counterparts. Surgery performed according standard techniques did not increase significantly the number of errors in any of the tested categories. Location of the tumor (hemispheric vs midline) was not a determinant of the performance of the children. The patient tested up to 2 years after surgery demonstrated a progressive improvement in the performance of visual and auditory memory tasks. Our results provide further evidence that the cerebellum plays a role in the integration of auditory stimuli.

Medulloblastoma presenting as blindness of rapid evolution. A case report.

An 18-year-old man reported rapid decrease of visual acuity that progressed to total blindness in 1 month. Computed tomographic scanning showed two neoplastic masses: a large one, intra- and suprasellar, and a smaller cerebellar nodule. Histologically, the former proved to be a large metastasis of the small cerebellar medulloblastoma, which infiltrated and compressed the chiasm. Direct compression of the optic pathways by metastasis of a medulloblastoma is a rare event.

Meduloblastomas: análise de 17 casos / Medulloblastomas: report of 17 cases

Os autores apresentam 17 casos de meduloblastomas operados no Serviço de Neurocirurgia do Hospital Cristo Redentor no período de 11 anos (1976-1986). Foi observada maior incidência em pacientes jovens (10 meses a 29 anos de idade) e no sexo masculino (2:1). Os sinais e sintomas mais comuns foram os relativos a hipertensäo intracraniana (HIC) e distúrbios cerebelares, sendo que o intervalo de tempo médio entre o início da sintomatologia e a hospitalizaçäo foi de dois meses e meio. Todos os pacientes foram submetidos a uma craniectomia suboccipital em posiçäo sentada, sendo a derivaçäo ventrículo-peritoneal (DVP) realizada previamente em cinco casos. A mortalidade pós-operatória foi de 29,4%

Meduloblastoma y astrocitoma de fosa posterior / Meduloblastoma and cerebelar astrocytoma

Se presenta la asociación de dos tumores, histológicamente diferentes, ubicados en la fosa posterior de un mismo paciente; y que se hicieron manifiestos con cinco años de diferencia y un tratamiento quirúrgico y radioterápico de por medio. Casos similares han sido observados por otros autores, no obstante es la primera vez que se comunica esta asociación en nuestro país. La probabilidad por azar de que estos dos tumores se presenten en la vida de una persona es de uno en 10 billones. Hay evidencias en la literatura relacionada, tanto clínica como de laboratorio, que implican a la radioterapia en la aparición del segundo tumor; y que en este caso corresponde a un astrocitoma fibrilar G II. En este caso habría actuado, ya sea dejando un remanente diferenciado hacia la línea astrocítica del tumor inicial, que era un meduloblastoma o induciendo un nuevo tumor en tejido nervioso previamente sano

[Developmental Gerstmann syndrome associated with cerebellar neoplasm. Report of a case and review of the literature]. / Sindrome de Gerstmann de desenvolvimento associada a neoplasia cerebelar. Relato de um caso e revisão da literatura

A Developmental Gerstmann syndrome in a 7 years-old-boy with hyperactivity, short attention span, acalculia, agraphia, right-left confusion, finger agnosia and constructional apraxia is reported. An initial trial with methylphenidate was done with good improvement regarding hyperactivity, attention span and constructional apraxia. In the clinical course developed a cerebellar syndrome and intracranial hypertension. Surgical exploration of the cerebellum discovered a medulloblastoma. The author believes that this is the first described association of Developmental Gerstmann syndrome and cerebellar neoplasia. The clinical findings, the etiology and the topography of the Gerstmann syndrome are discussed.