Luciana Porto

Cerebrovascular complications of L-asparaginase in the therapy of acute lymphoblastic leukemia.

l-asparaginase is frequently used in combination therapy for the treatment of lymphoid malignancies. We report 5 children aged between 8 and 14 years with neurologic complications presenting with headache and seizures during the first three weeks of l-asparaginase treatment. Three patients had venous thrombosis, one presented a parenchymal hemorrhage, and one showed a peculiar encephalopathy with extended cortical and subcortical lesions suggesting a neurotoxic reaction. Decreased fibrinogen and antithrombin III levels were found. Early MRI is critical even in cases with mild neurologic symptoms. Diagnosis should be followed by early cessation of l-asparaginase application.

Cognitive Phenotype in Ataxia-Telangiectasia

BACKGROUND Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have not been examined in detail for neuropsychologic changes. Such studies may contribute to the further understanding of ataxia-telangiectasia and to the role of the cerebrocerebellar system in the development of cognitive function in childhood. METHODS Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features. Results were compared with those of healthy control subjects and with standard norms. RESULTS Patients in AT-I group scored low average compared with standard norms on all tests and were impaired compared with healthy control subjects for verbal intelligence quotient (P < 0.001), vocabulary and comprehension (P = 0.007), processing speed (P = 0.005), visuospatial processing (P = 0.020), and working memory (P = 0.046). Patients in AT-II group scored below average compared with standard norms on all tests and were impaired compared with control subjects for attention (P < 0.001), working memory (P < 0.001), and abstract reasoning (P < 0.001). Comprehension scores were lower for patients in AT-II than in AT-I group (P = 0.002), whereas vocabulary scores showed no difference between groups (P = 0.480). CONCLUSION Cognitive impairments in ataxia-telangiectasia present early, coinciding with cerebellar pathology and are characteristic of the cerebellar cognitive affective syndrome. Widespread and deeper cognitive deficits manifest in later stages of ataxia-telangiectasia when additional noncerebellar pathology develops. These results are the first indications of distinct cerebellar and extracerebellar and/or subcortical contributions to the range of cognitive domains affected in ataxia-telangiectasia and need to be confirmed in future studies.

Rhinocerebral zygomycosis in a young girl undergoing allogeneic stem cell transplantation for severe aplastic anaemia

We report on a 10‐year‐old girl with severe aplastic anaemia who developed rhinocerebral infection caused by Absidia corymbifera and a possible co‐infection caused by Alternaria alternata. Despite prolonged neutropenia, therapy with liposomal amphotericin B and posaconazole improved the clinical condition. Subsequently, the girl underwent allogeneic haematopoietic stem cell transplantation (HSCT) for the underlying disease, but the fungal infection remained under control with the antifungal treatment. No severe side effect of the antifungal drugs was noted. Unfortunately, the girl died 5 months after HSCT due to disseminated adenovirus infection.

Acute necrotising encephalopathy of childhood after exanthema subitum outside Japan or Taiwan.

Abstract Acute necrotising encephalopathy of childhood (ANE) is an uncommon disease which predominantly affects infants and young children living in Japan and Taiwan. A multifocal encephalopathy with symmetrical lesions in the thalamus, tegmentum of the brain stem, cerebral periventricular white matter and cerebellar medulla is characteristic. We present the imaging features in a 4-year-old Japanese boy who had been living in Germany for 21/2 years before presentation.

Human herpes virus-6 DNA in cerebrospinal fluid of children undergoing therapy for acute leukaemia

alone (54Æ4%) (P < 0Æ01). Those treated with XRT + surgery (81Æ9%) had a better 5-year DSS than those treated with surgery alone (79Æ6%) or XRT alone (71Æ9%) (P < 0Æ01). However, multivariate analysis did not identify treatment modality as a prognostic factor. Dores et al (2009) did not comment on the cause of death in their analysis of the SEER database. We found that the major cause of death was multiple myeloma in 277 patients (49Æ64%). However, analysis of cause of death between groups revealed statistically significant differences in cause of death between age group, gender and location. Patients between 40 and 60 years old were most likely to die of myeloma (57Æ9%) followed by 48Æ2% of patients >60 years (48Æ2%) and patients £40 (35Æ3%) (P < 0Æ01). Females died more frequently of myeloma (57Æ6%) than males (45Æ0%) (P < 0Æ01). 32Æ8% of SEP patients died of myeloma as compared to 57Æ7% of SBP patients (P < 0Æ01). The SEER database unfortunately does not provide data on details of any systemic therapy delivered. However, it may be possible to improve survival by offering adjuvant systemic therapy especially in patients with poor prognostic factors. Prospective, randomized trials comparing adjuvant chemotherapy versus observation alone after local therapy are needed for solitary plasmacytoma. Giridharan Ramsingh Paul Mehan Daniel Morgensztern Jingqin Luo Ravi Vij Washington University School of Medicine, Oncology, Washington University School of Medicine, Internal Medicine, John Cochran Veterans Affairs Medical Center, Hematology/Oncology, and Washington University School of Medicine, Biostatistics, St. Louis, MO, USA. E-mail: gramsing@dom.wustl.edu

MR spectroscopy differentiation between high and low grade astrocytomas: a comparison between paediatric and adult tumours.

OBJECTIVE To investigate whether pathologically similar astrocytomas in adults and children may also show metabolic similarities in proton magnetic resonance spectroscopy ((1)H-MRS) and whether the MRS data could help to differentiate between low and high grade gliomas for the different groups. MATERIAL AND METHODS Twelve children (5 WHO II astrocytomas, 7 WHO III astrocytomas) and 37 adults (21 WHO II astrocytomas, 16 WHO III astrocytomas) were included in this study. MR spectroscopic data were evaluated retrospectively using normalized measures of total choline (tCho), N-acetyl-aspartate (NAA) and total creatine (tCr). These metabolites were used to differentiate between WHO II and WHO III astrocytomas in children and adults. Histopathological grading was performed using WHO criteria. (1)H-MRS was carried out prior to the commencement of any treatment. Signal intensities of tCho, NAA and tCr were normalized to their values in contralateral brain tissue. The resulting concentration ratios were then used to calculate the change in the intratumoural ratio of NAA to tCho. A Mann-Whitney U-Test was performed to evaluate differences within the respective groups. RESULTS In both groups, loss of NAA and increase of tCho were more pronounced in WHO III than in WHO II astrocytoma. The best discriminator to differentiate between low and high grade gliomas was found to be the ratio of NAA/tCho (p < 0.01). CONCLUSION The normalized metabolite signal intensities ratio NAA to tCho is the most accurate in differentiating between low and high grade astrocytomas in both children and adults.

Morphometry and diffusion MR imaging years after childhood traumatic brain injury

OBJECTIVE Our goal was to detect possible unrecognized injury in cerebral white matter (WM) in adult survivors of traumatic brain injury (TBI) during childhood, who showed no detectable axonal injury or chronic contusion on late conventional MRI. MATERIAL AND METHODS We used voxel-based morphometry (VBM) to detect subtle structural changes in brain morphology and diffusion-tensor imaging (DTI) to non-invasively probe WM integrity. By means of VBM and DTI we examined a group of 12 adult patients who suffered from childhood closed head injury without axonal injury on late conventional MRI. RESULTS Patients sustained complicated mild or moderate-to-severe TBI with a mean of 7 points based on the Glasgow Coma Scale. The mean time after trauma was 19 years (range 7-31 years). For VBM, group comparisons of segmented T1-weighted grey matter and WM images were performed, while for DTI we compared the fractional anisotropy and mean diffusivity (MD) between the groups. Patients presented with higher MD in the right cerebral white matter, bilaterally in the forceps major and in the body and splenium of the corpus callosum. These findings were supported by VBM, which showed reduced WM volume bilaterally, mainly along the callosal splenium. CONCLUSION Our results indicate that persistent focal long-term volume reduction and underlying WM structural changes may occur after TBI during childhood and that their effects extend into adulthood. Normal late conventional MR findings after childhood TBI do not rule out non-apparent axonal injury.

Tay's syndrome: MRI

Abstract Tays syndrome is a trichothiodystrophy associated with congenital ichthyosis. We report the findings on MRI and spectroscopy in a young girl with sparse, short, ruffled hair, dry skin and delayed milestones. T2-weighted images showed prominent diffuse confluent increase in signal symmetrically in all the supratentorial white matter. These findings are similar to those in a previously described case, and consistent with dysmyelination. Spectroscopy showed increased myoinositol and decreased choline.

Quantitative T2, T2*, and T2′ MR imaging in patients with ischemic leukoaraiosis might detect microstructural changes and cortical hypoxia

IntroductionQuantitative MRI with T2, T2*, and T2′ mapping has been shown to non-invasively depict microstructural changes (T2) and oxygenation status (T2* and T2′) that are invisible on conventional MRI. Therefore, we aimed to assess whether T2 and T2′ quantification detects cerebral (micro-)structural damage and chronic hypoxia in lesions and in normal appearing white matter (WM) and gray matter (GM) of patients with ischemic leukoaraiosis (IL). Measurements were complemented by the assessment of the cerebral blood flow (CBF) and the degree of GM and WM atrophy.MethodsEighteen patients with IL and 18 age-matched healthy controls were included. High-resolution, motion-corrected T2, T2*, and T2′ mapping, CBF mapping (pulsed arterial spin labeling, PASL), and segmentation of GM and WM were used to depict specific changes in both groups. All parameters were compared between patients and healthy controls, using t testing. Values of p < 0.05 were accepted as statistically significant.ResultsPatients showed significantly increased T2 in lesions (p < 0.01) and in unaffected WM (p = 0.045) as well as significantly increased T2* in lesions (p = 0.003). A significant decrease of T2′ was detected in patients in unaffected WM (p = 0.027), while no T2′ changes were observed in GM (p = 0.13). Both unaffected WM and GM were significantly decreased in volume in the patient-group (p < 0.01). No differences of PASL-based CBF could be shown.ConclusionNon-invasive quantitative MRI with T2, T2*, and T2′ mapping might be used to detect subtle structural and metabolic changes in IL. Assessing the grade of microstructural damage and hypoxia might be helpful to monitor disease progression and to perform risk assessment.

Leptomeningeal metastases in pediatrics : magnetic resonance image manifestations and correlation with cerebral spinal fluid cytology

Background:  Detection of leptomeningeal metastases is fundamental to a complete evaluation of central nervous system (CNS) or non‐CNS tumor with suspected involvement of the neuroaxis. Our purpose was to assess the appearances of different magnetic resonance (MR) sequences in the diagnosis of leptomeningeal metastases and correlate those positive findings with the cerebral spinal fluid (CSF) cytology results.