Influence of thermal cycles and disinfection on the roughness, microhardness and color of PETG/TPU and PMMA.

BACKGROUND: Occlusal splints can protect teeth during bruxism, preventing tooth wear, as well as during sports activities, shielding them from impacts. OBJECTIVES: To verify the influence of thermal cycles and disinfection on the roughness, microhardness and color of polyethylene terephthalate glycol/thermoplastic polyurethane (PETG/TPU) and poly(methyl methacrylate) (PMMA). MATERIAL AND METHODS: Thirty-six PETG/TPU samples and 36 PMMA samples were prepared (ø10 mm × 3 mm). Six groups were created according to the material and the disinfection method used (n = 12 each): PETG/TPU (glister), PETG/TPU (hypochlorite), PETG/TPU (soap), PMMA (glister), PMMA (hypochlorite), and PMMA (soap). Roughness, Knoop microhardness and color evaluations were performed before the experiments (T1), after thermocycling (T2) and after disinfection (T3). Three-way repeated measures analysis of variance (ANOVA) and Tukey's test were used for statistical evaluations. RESULTS: For roughness and color, ANOVA showed statistical significance based on the interaction between thermal cycling, material and disinfectant factors. In terms of Knoop microhardness, ANOVA showed statistical significance based on the interaction between thermal cycling and material factors. CONCLUSIONS: Roughness results were clinically acceptable in all groups at all time points, except the PETG/TPU and PMMA groups disinfected with hypochlorite. Microhardness significantly increased for both materials after thermal cycling, and at all time points, the microhardness of PMMA was significantly higher than that of PETG/TPU. After thermal cycling, the color changes were clinically unacceptable in all groups.

Bilateral adrenal primary tumor in Stage 4S neuroblastoma: The Italian experience and review of the literature.

Bilateral adrenal neuroblastoma (NB) is rare and is mainly stage 4S. Its incidence, presenting features, management, and outcome have not been fully defined yet. We searched the Italian NB Registry (RINB) for stage 4S NB infants with bilateral adrenal primary tumor to compare them with stage 4S NB with unilateral tumor. Between 1979 and 2016, the RINB enrolled 3731 NB patients aged 0-18 years including 317 infants (8.5%) diagnosed with stage 4S NB. Eleven/317 (3.5%) had a bilateral adrenal primary tumor (Group 1) and 190/317 (59.9%) had a unilateral tumor (Group 2). Group 1 infants were significantly younger (51 vs. 89 days) but were comparable with Group 2 for any other presenting features. In the absence of specific protocols, upfront treatment was based on symptoms, size of adrenal tumors, and biology, and consisted of observation in 5 cases, radiotherapy in one, chemotherapy in 2, and surgery in 3. Five/11 developed progression and 2 of them, both with MYCN amplification, died. The 5-year EFS rates of Group 1 and 2 were 54.5% vs. 73.3% (P=.14) and 5-year OSs were 81.8% and 89.4%, respectively (P=.44). Our data support the hypothesis that 4S NB infants with bilateral adrenal tumors can have favorable outcome with personalized therapeutic approach. The three patients with MYCN amplified tumor benefited from upfront aggressive chemotherapy, in accordance with current protocols. Because of the rarity of this intriguing form of neuroblastoma, collaborative prospective studies are warranted, especially in view of gaining a better insight on its biological and genetic features.

Metastatic progression in infants diagnosed with stage 4S neuroblastoma. A study of the Italian Neuroblastoma Registry.

PURPOSE: Stage 4S neuroblastoma, a tumor affecting infants, is characterized by the capacity to regress spontaneously and high cure rate. About a third of these infants undergo tumor progression requiring antitumor treatment and 10-15% eventually die. In case of metastatic progression, it may occur either at 4S sites (mainly liver) or sites characterizing stage 4 (mainly bone). Aim of this study was to estimate incidence, presenting features and outcome of infants who progressed to stage 4S or stage 4 sites. PATIENTS: Of 280 Italian infants diagnosed with stage 4S neuroblastoma between 1979 and 2013 and registered in the Italian Neuroblastoma Registry, 268 were evaluable for this study, of whom 57 developed metastatic progression. RESULTS: Progression to stage 4S sites occurred in 29/268 infants (10.8%) (Group A) and to stage 4 in 28/268 (10.4%) (Group B). No significant difference was observed between the two groups at the time of diagnosis. At the time of progression, Group A infants were younger (7.3 vs 14.4 months, P = .001) and had a shorter interval from diagnosis to progression (3.8 vs 9.6 months, P = .001). Survival after progression was worse for Group B infants (45% vs 69%, P = .058) and was associated with age at diagnosis lower than 2 months (P = .005) and adrenal primary tumor site (P = .008). Survival rates increased for both groups along the study period. CONCLUSIONS: Infants who progressed to stage 4 did worse, possibly in relation to older age at progression and longer interval between diagnosis and progression. Large prospective studies of these patients may lead to more effective treatments.

Resection of primary tumor in stage 4S neuroblastoma: a second study by the Italian Neuroblastoma Group.

PURPOSE: To clarify the role of primary tumor resection in stage 4S neuroblastoma. METHODS: We investigated a cohort of 172 infants diagnosed with stage 4S neuroblastoma between 1994 and 2013. Of 160 evaluable patients, 62 underwent upfront resection of the primary tumor and 98 did not. RESULTS: Five-year progression-free and overall survival were significantly better in those who had undergone upfront surgery (83.6% vs 64.2% and 96.8% vs 85.7%, respectively). One post-operative death and four non-fatal complications occurred in the resection group. Three patients who had not undergone resection died of chemotherapy-related toxicity. Thirteen patients underwent late surgery to remove a residual tumor, without complications: all but one alive. Outcomes were better in patients diagnosed from 2000 onwards. CONCLUSION: Infants diagnosed with stage 4S neuroblastoma who underwent upfront tumor resection had a better outcome. However, this result cannot be definitely attributed to surgery, since these patients were selected on the basis of their favorable presenting features. Although the question of whether to operate or not at disease onset is still unsolved, this study confirms the importance of obtaining enough adequate tumor tissue to enable histological and biological studies to properly address treatment, to achieve the best possible outcome.

A Review of Infants With Localized Neuroblastoma That Evolve to Stage 4s Disease.

The authors describe a newborn diagnosed with localized neuroblastoma that evolved to stage 4s at the age of 5 months. Peculiar features of the case included a bilateral adrenal primary, the skin as the only metastatic site, and the development of a muscular lesion late in the clinical course. The patient underwent left adrenalectomy and all other lesions regressed without further therapy. The case prompted a search for similar cases both in the Italian Neuroblastoma Registry and in the literature. All patients identified, although variously treated, survived with the exception of the 2 with MYCN gene amplification. We conclude that infants with neuroblastoma who undergo a transition from a localized to stage 4s disease could be less rare than expected. In the absence of unfavorable biology, a wait-and-see policy with strict follow-up could be adopted for these patients, avoiding potentially damaging systemic therapy.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

BACKGROUND: Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. OBJECTIVE: The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. MATERIALS AND METHODS: This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. RESULTS: A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). CONCLUSION: Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.

White matter disruption is associated with persistent seizures in tuberous sclerosis complex.

BACKGROUND AND AIMS: White matter is diffusely altered in tuberous sclerosis complex (TSC), and these alterations appear to be more evident in subjects with a more severe neurologic phenotype. However, little is known on the correlation between white matter alterations and epilepsy in TSC. The aims of this study were to evaluate the effects of early onset and refractory seizures on white matter by using diffusion tensor imaging (DTI). METHODS: We enrolled 20 children with TSC and epilepsy onset in the first 3years of life and grouped them according to seizure persistence or freedom. All patients underwent brain MRI with DTI. Specific ROIs have were placed to generate tracks to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Statistical analysis was performed by ANOVA. RESULTS: Children with persistent seizures presented an overall reduced FA, with statistically significant differences on the cingulum (right p=0.003, left p=0.016), the left cerebral peduncle (p=0.020), the superior cerebellar peduncles (right p=0.008, left p=0.002), the posterior limbs of internal capsule (right p=0.037, left p=0.015), the external capsule (right p=0.018, left p=0.031), the inferior frontooccipital fasciculus (right p=0.010, left p=0.026), and the temporal trunk (right p=0.017, left p=0.001). CONCLUSIONS: Our study demonstrated that children with persistent seizures present more significant alterations of brain connectivity in areas crucial for global cognitive maturation, executive functions, and verbal abilities, implying a higher risk of cognitive impairment, attention-deficit hyperactivity disorder, and autism.

Cerebral sinovenous thrombosis (CSVT) in children: what the pediatric radiologists need to know.

Cerebral sinovenous thrombosis (CSVT) is a relatively uncommon and potentially life-threatening condition in childhood, occurring in various clinical settings. Nowadays, however, it is increasingly diagnosed as related to many causes, likely due to greater clinical awareness and improvement of neuroradiologic techniques. The prompt diagnosis is an important goal to significantly reduce the risk of acute complications and long-term sequelae. The purpose of this narrative overview is to provide a useful educational tool in daily clinical practice for radiologists with a broad perspective of CSVT including a discussion of more common potential pitfalls related to misinterpretation of images in children. This paper will also review the normal venous anatomy, its variants, risk factors that contribute to cause CSVT (neonates with their specific causes of CSVT are not included in this review) and the practical imaging feature of cerebral sinovenous thrombosis on MRI and CT. Finally, a brief overview of frequent and severe CSVT conditions in children with key points in imaging is shown.

Atypical teratoid/rhabdoid tumor (ATRT) arising from the 3rd cranial nerve in infants: a clinical-radiological entity?

Atypical teratoid/rhabdoid tumor (ATRT) is a rare embryonal tumor of the central nervous system with preponderance in very young children, the majority of whom are younger than 3 years of age at diagnosis. Historically, outcomes of this aggressive disease, even with extensive multimodal therapy, have been dismal. Recent improvements have come from therapies directed exclusively towards ATRT, but misdiagnosis or delays in the correct diagnosis lead to significantly worse survival rates. ATRTs most commonly occur supratentorially but have been described in virtually all central nervous system locations, including the cerebellopontine angle cistern, meninges, and spinal canal, and extradural locations. ATRTs originating from cranial nerves are rare. Here, we describe three cases of solitary ATRT arising from the 3rd cranial nerve (CN III) or close to its origin in the midbrain, all of which presented in patients within 6 months of birth, with isolated unilateral oculomotor nerve palsy and strikingly similar magnetic resonance imaging (MRI) features. These MRI features include IV contrast enhancement, relative T2 hyposignal, and restricted water diffusion on apparent diffusion coefficient images, findings which are consistent with angiogenesis and high cellularity, and hence, suggestive of malignancy. We conclude that ATRT should be placed high on the differential diagnosis list when encountering a young infant presenting with isolated, unilateral 3rd nerve palsy and a small, solitary tumor arising from CN III that demonstrates malignant conventional and diffusion-weighted imaging features on MRI.

Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

BACKGROUND: The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). PROCEDURE: 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. RESULTS: In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. CONCLUSIONS: In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning.

Neuroblastoma with symptomatic epidural compression in the infant: the AIEOP experience.

BACKGROUND: Symptoms of epidural compression (SEC) in children with neuroblastoma (particularly infants) may be misinterpreted, leading to delay in diagnosis. PATIENTS AND METHODS: Clinical, imaging and follow-up data of 34 infants with neuroblastoma and SEC diagnosed between 2000 and 2011 at Italian AIEOP centers were retrieved and reviewed. RESULTS: Median age at initial SEC was 104 days (IQR 47-234). Main symptoms included motor deficit (85.3%), pain (38.2%), bladder and bowel dysfunctions (20.6% each). In the symptom-diagnosis interval (S-DI) (median, 12 days; IQR 7-34), the frequency of grade 3 motor deficit increased from 11.8% to 44.1% and that of bladder dysfunction from 20.6% to 32.4%. S-DI was significantly longer (P = 0.011) for patients developing grade 3 motor deficit. First treatment of SEC was neurosurgery in 14 patients, and chemotherapy in 20. SEC regressed in 11 patients (32.3%), improved in 9 (26.5%), and remained stable in 14 (41.2%), without treatment-related differences. Median follow-up was 82 months. At last visit, 11 patients (32.3%) were sequelae-free while 23 (67.7%) had sequelae, including motor deficit (55.9%), bladder (50.0%) and bowel dysfunctions (28.4%), and spinal abnormalities (38.2%). Sequelae were rated severe in 50% of patients. Severe sequelae scores were more frequent in patients presenting with spinal canal invasion >66% (P = 0.039) and grade 3 motor deficit (P = 0.084). CONCLUSIONS: Both neurosurgery and chemotherapy provide unsatisfactory results once paraplegia has been established. Sequelae developed in the majority of study patients and were severe in a half of them. Greater awareness by parents and physicians regarding SEC is warranted.

Neuroblastoma in the adult: the Italian experience with 21 patients.

BACKGROUND: Neuroblastoma in the adult is rare. No established therapeutic guidelines exist for these patients and the literature on this issue is scant and contradictory. MATERIALS AND METHODS: Between 1986 and 2011, 21 adults (18 to 38 y; median, 23) diagnosed with neuroblastoma were referred to our hospital. Three of the 21 were classified as neuroblastoma, not otherwise specified, 13 as neuroblastoma, schwannian stroma-poor, and 5 as ganglioneuroblastoma, nodular. Nine patients had a resectable (stage 1/2) and 6 an unresectable primary tumor (stage 3); 6 had disseminated disease (stage 4). RESULTS: Of 9 stage 1/2 patients, 6 underwent surgery alone (2 survive, 4 died), 2 received adjuvant chemotherapy (both survive), and 1 received radiation therapy (alive). Four of the 6 stage 3 patients received chemotherapy and died, 1 underwent partial tumor resection only and died, and 1 received radiation therapy after partial tumor resection and is alive. The 6 stage 4 patients received chemotherapy with/without radiotherapy, and all died. Event-free survival at 10 years was 33.3% for stage 1/2, 16.7% for stage 3, and 0% for stage 4 patients. The 10-year overall and event-free survival rates were 39.8% and 19.1%, respectively. CONCLUSIONS: The outcome of neuroblastoma in adults is poorer than in younger patients at all stages. The clinical course seems modestly influenced by therapy.

Conventional magnetic resonance imaging and diffusion tensor imaging studies in children with novel GPR56 mutations: further delineation of a cobblestone-like phenotype.

GPR56-related bilateral frontoparietal polymicrogyria (BFPP) is a rare recessively inherited disorder of neuronal migration caused by mutations of GPR56. To better delineate the clinical, molecular, and neuroradiological phenotypes associated with BFPP, we performed conventional magnetic resonance imaging and diffusion tensor imaging studies in a series of prospectively enrolled patients carrying novel GPR56 mutations. All subjects with GPR56-related BFPP showed a characteristic morphological pattern, including abnormalities of the cerebellar cortex with cerebellar cysts located at the periphery, a mildly thick corpus callosum, and a flat pons. Significant alterations of myelination and white matter tract abnormalities were documented. The present study confirms the phenotypic overlap between GPR56-related brain dysgenesis and other cobblestone-like syndromes and illustrates the contribution of 3D neuroimaging in the characterization of malformations of cortical development.

Symptomatic epidural compression in infants with neuroblastoma: a single-center experience with 5 cases.

Infants affected by neuroblastoma with symptomatic epidural compression require early diagnosis and appropriate treatment to avoid severe late complications. However, no established guidelines are available regarding the optimal treatment of these patients. We describe 5 such infants. The interval between the onset of symptoms and tumor diagnosis was 3 to 8 days in 4/5 cases. None developed paraplegia before or after treatment. Treatment for epidural compression included first-line laminoplasty followed by chemotherapy in 3 patients, and chemotherapy first in the remaining 2. To date, all are alive and none have developed severe complications after a follow-up of 9 to 39 months (median, 20).

MR differential diagnosis of acute deep grey matter pathology in paediatric patients.

A high metabolic demand, rich vascularization and high concentrations of ionic elements leading to the generation of oxygen free radicals, give to the deep grey matter (DGM) nuclei specific susceptibility to both acute and chronic insults, especially in paediatric patients. Reaching a diagnosis in the early stages of acute diseases in many patients is crucial for instigating prompt specific therapy leading to a favourable outcome. On the basis of a review of a 10-year in-house database and a review of the literature on CNS pathology involving the DGM nuclei in paediatric patients, we summarize the MR findings and clinical clues that may help the radiologist in the difficult differential diagnosis process. The terms "acute" and "chronic" refer to the clinical onset of the disease. MR imaging allows the detection of an injury, determination of its precise anatomical location and characterization of the signal changes. This, combined with a knowledge of specific MRI patterns, may be a roadmap to a definite diagnosis. Clinical history, physical and laboratory findings, timing of the MR examination and advanced MR imaging techniques (diffusion-weighted imaging and (1)H-MR spectroscopy), are crucial in some patients.

Status epilepticus as a main manifestation of posterior reversible encephalopathy syndrome after pediatric hematopoietic stem cell transplantation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a severe neurological complication after pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Seizures are a common manifestation of PRES. Status epilepticus (SE) is a potentially life-threatening event rarely described in this condition. The aim of this study was to describe the clinical and electroencephalographic features of SE as a manifestation of PRES in children after allo-HSCT. PROCEDURE: We retrospectively identified episodes of SE as a consequence of PRES out of 211 children who received allo-HSCT in the period January 2000 to June 2008. RESULTS: PRES was diagnosed in 11 patients. We identified 12 episodes of SE associated to PRES in 10 patients. Nonconvulsive SE (NCSE) involving posterior regions of the brain (confirmed by EEG monitoring) was observed in four cases; convulsive SE (CSE) was observed in eight cases. Gaze deviation, oculoclonic movements, nystagmus, and altered mental status were the main clinical signs during NCSE and preceded CSE in 5/8 cases. Most patients needed intensive care management. A complete normalization of neurological examination and EEG pattern was observed in all patients after SE and withdrawal of causative agent. Follow-up MRI showed complete resolution of brain edema in all patients. CONCLUSIONS: Our experience shows that SE is more frequent than previously reported and is often the main manifestation of PRES after pediatric allo-HSCT. Looking for suggestive clinical signs as well as routine use of EEG monitoring may allow prompt recognition of SE and therapy of both SE and PRES.

Hemimegalencephaly associated with congenital infiltrating lipomatosis of the face: a case report.

Hemimegalencephaly (HME) is a rare congenital malformation of the brain, grossly characterized by enlargement and overdevelopment of one cerebral hemisphere. We describe a 16-month-old patient with facial asymmetry caused by congenital infiltrating lipomatosis of the face (CILF) associated with ipsilateral HME. Although HME has been described as part of different syndromic diseases, the association of HME with CILF has been rarely reported. Our case and literature review suggest that when the diagnosis of CILF is suspected or established, the possible presence of associated HME has to be considered and a magnetic resonance imaging (MRI) must be performed even in absence of neurological features, not always present in early stages. MRI also demonstrates the involvement of intracranial structures outside the affected cerebral hemisphere, such as brain stem, cerebellum, cranial nerves, and blood vessels. In our patient, computed tomography of the brain provided detailed information on osseous hypertrophy and skull-base foramina enlargement.

Cyto-morphologic evaluation of bone marrow in infants with disseminated neuroblastoma.

We studied the prevalence and degree of tumor cell infiltration (TCI) in bone marrow (BM) aspirates of 89 infants with stage 4/4 S neuroblastoma and correlated them with MYCN gene status and patient outcome. TCI was scored 0, +, ++, and +++, the last corresponding to an infiltration greater than 10%. TCI 0 was more frequent in stage 4 than in stage 4 S. TCI + and ++ were equally represented. TCI +++ was found only in 9 patients, all with typical stage 4 features (bone or lung involvement). Overall survival was not significantly influenced by the presence and degree of TCI.

Neonatal hemifacial spasm and fourth ventricle mass.

Congential hemifacial spasm is a rare condition that is characterized by the occurrence of paroxysmal hemifacial contractions in neonates. We review the clinical, neurophysiological, neuroimaging, and histopathological findings, as well as the differential diagnosis, therapeutic approach, and outcome of all the described cases. Moreover, we report two new cases including the ictal video-electroencephalography recordings. Hemifacial spasm starts early in life, and is characterized by unilateral, involuntary, irregular tonic or clonic contractions of muscles innervated by the seventh cranial nerve. Hemifacial spasm is associated with eyelid blinking, and sometimes with breathing irregularities, hyperventilation, and/or other neurological manifestations (dystonic movements, nystagmus). Interictal and ictal video-electroencephalography did not reveal epileptiform abnormalities. In all cases, brain magnetic resonance imaging showed a mass involving the cerebellar peduncle, the cerebellar hemisphere, or the floor of the fourth ventricle. The semiology of the paroxysmal attacks is probably due to the activation of cranial nerve nuclei through intralesional hypersynchronous discharges, as shown by the intraoperative recordings and functional brain imaging described in the literature. We point out the importance of identifying such seizures in order to make an early diagnosis of the underlying cerebral lesion.