Bernt Johan Due-Tønnessen

Persistent Cognitive Dysfunction Secondary to Cerebellar Injury in Patients Treated for Posterior Fossa Tumors in Childhood

Traditionally, the cerebral hemispheres have been regarded as the region of the brain responsible for cognitive functions, while the cerebellum has been considered to be primarily involved in motor functions. Recent studies focus also on the possible involvement of the cerebellum in neurocognitive functions. The aim of this study was to determine the neuropsychological profile of young adults treated for a posterior fossa tumor in childhood and look for possible support for the presence of the so-called ‘cerebellar cognitive affective syndrome’ in these patients. Two groups of young adults were studied. The astrocytoma group (n = 12) had been treated for a low-grade cerebellar astrocytoma with surgery alone (mean age at surgery was 8.6 years and mean age at neuropsychological testing was 23.5 years). The medulloblastoma group (n = 11) had been treated with surgery followed by radiotherapy and chemotherapy (mean age at surgery was 6.1 years and mean age at neuropsychological testing was 23.1 years). The neuropsychological test battery comprised measures of intelligence, motor function, attention, psychomotor speed, verbal memory and visual memory. The medulloblastoma group performed poorer than the astocytoma group on all neuropsychological measures except one. Nonetheless, the astrocytoma group also had impaired scores compared with standard norms on measures of motor speed, attention and executive function. No significant correlation between age at time of treatment and grade of neuropsychological impairment was found in the astrocytoma group, though there was a tendency that young age at time of treatment correlated with better outcome on IQ measures. In the medulloblastoma group, age was significantly correlated with outcome, for both IQ and degree of neuropsychological impairment. For this group, young age at time of treatment indicated a worse outcome. Conclusions: Persistent cognitive dysfunction was detected in patients treated for posterior fossa medulloblastoma and cerebellar astrocytoma. The astrocytoma group was treated with surgery alone, indicating that a cerebellar lesion can result in cognitive dysfunction. Thus, this study gives support to the existence of the cerebellar cognitive affective syndrome. Follow-up of all patients treated for posterior fossa tumor in childhood should include an extensive neuropsychological testing at regular intervals. This may be of benefit for school planning and later work planning.

Long-Term Outcome after Resection of Benign Cerebellar Astrocytomas in Children and Young Adults (0–19 Years): Report of 110 Consecutive Cases

The objective of this retrospective study was to present long-term follow-up data for 110 consecutive children and young adults treated for a benign cerebellar astrocytoma at our institution between 1960 and 2001. Mean age at presentation was 8.9 years. The total surgical mortality was 9%, but declined from 16% in 1960–1977 to 0% in 1988–2001. At the close of the study 97/110 patients were still alive. Nine deaths were surgery related, 2 patients died of shunt-related causes and 2 patients died due to tumor recurrence. Five-, 10- and 25-year survival were 90, 89 and 85%, respectively. Multiple Cox regression analysis showed that tumor infiltration of the brain stem and the time period of surgery were the only explanatory variables significantly associated with survival. Five-year survival improved from 79% in the time period of 1960–1977 to 100% in the time period of 1988–2001. Tumor recurrence after total tumor resection was observed in 5 of 76 (7%) evaluable patients. Growth of residual tumor after subtotal tumor resection was observed in 7 of 26 (27%) evaluable patients. Recent follow- up MR revealed regression of residual tumor in 14 of 16 patients. Only 5 of these patients had received radiotherapy. Thus, spontaneous regression of residual tumor is a more frequent event than growth of residual tumor. The functional outcome was favorable in 82% of the patients [Karnofsky performance index (KPI) ≧90]. Eighteen percent of the patients had moderate to severe disabilities (KPI 50–80). Conclusions: Benign cerebellar astrocytoma is a surgical disease where the prognosis with respect to both survival and functional outcome is favorable. Spontaneous regression of residual tumor is frequently encountered, allowing for observation of residual tumors instead of performing a second resection in cases where a second resection carries a high risk of neurological sequelae.

Choroid plexus tumors in children and young adults: report of 16 consecutive cases.

Abstract Choroid plexus tumors are rare intraventricular tumors, and they represent 2–4% of brain tumors in children. This single-institution retrospective study involves 16 consecutive choroid plexus tumors: 13 papillomas and 3 carcinomas. Tumor locations were the lateral ventricles in 13 cases, the third ventricle in 2 cases and the fourth ventricle in 1 case. The mean age at presentation was 3.1 years. Two patients died of perioperative blood loss. Five-year survival was 85% with papillomas and 33% with carcinomas. None of the papillomas recurred after total tumor resection, and the functional outcome in long-term survivors after papilloma surgery was excellent in 92% of the cases. Two of the carcinoma patients had disseminated disease. Fifty percent of the patients had persistent hydrocephalus after tumor resection, and these required cerebrospinal fluid diversion.

Posterior fossa medulloblastoma in children and young adults (0–19 years): survival and performance

Abstract The objective of this study was to present survival data and outcome status in the long-term survivors of a consecutive series of 111 children and young adults treated for posterior fossa medulloblastoma in our departments from 1960 to 1997. The total surgical mortality was 13%. The surgical mortality rate declined significantly during the time period overall, from 23% before 1970 to 0% after 1990. The 5-year survival rate for patients treated between 1960 and 1973 was 0%, while 5-year survival for patients treated after the introduction of systematic craniospinal radiation in 1974 was 53% . Thirty-four patients were alive at the close of this study, with a mean observation time of 13.5 years. Over half, 61%, of the patients had one or more major deficits/problems with respect to learning ability, power of locomotion, sociability, hobbies and relationships with the opposite sex. A younger age at the time of treatment was correlated with larger deficits/problems in these variables. The correlation between young age at the time of treatment and short final height was significant. The frequency of a second neoplasm was 14%. In all but 3 cases the major cause of permanent deficits/problems was radiation therapy.

Monobloc distraction osteogenesis in pediatric patients with severe syndromal craniosynostosis.

The management of the hypoplastic midface in syndromic craniosynostosis remains a great challenge. Frequently, patients have to be operated on numerous times to achieve a satisfactory end result, partially because of the limited skeletal advancement possible when using traditional surgical techniques. During the last decade, however, methods for gradual midfacial distraction have been presented, whereby greater advancements can be obtained. We present four children aged 17 months to 15 years with severe syndromal craniosynostosis in need of midface advancements because of severe respiratory obstruction or severe exophthalmos. These patients were complex cases with several previous craniofacial surgeries (mean of three times, range of two to six times) that yielded insufficient skeletal advancements. They were operated on with gradual monobloc advancements using the Modular Internal Distraction System. The mean length of operations was 370 minutes (range: 240-455 minutes), and the mean amount of perioperative blood transfusion needed was 1,300 ml (range: 280-2,700 ml) or 66.9 ml/kg (range: 31.1-94.9 ml/kg). The patient with the greatest number of previous operations also had the longest operation time as well as the most blood loss. The average midface advancement obtained was 25 mm (range: 20-30 mm), resulting in cessation or a significant decrease of preoperative respiratory problems, reduced exophthalmos, and improved facial profile. Apart from a local infection in one patient with a connective tissue disorder and several previous wound infections, no major postoperative complications were recorded. Distraction osteogenesis has become a versatile and safe technique that allows for large advancements of the midface.

Le Fort III distraction osteogenesis in syndromal craniosynostosis.

Midface distraction osteogenesis has become a valuable technique. Although outcome data are available from several craniofacial centers, information regarding perioperative and immediate postoperative course is scarce. This report describes seven children, aged 4 to 17 years, with syndromal craniosynostosis in need of midface advancements. Most were rather complex cases with several previous craniofacial surgeries (mean 4.4 times, range 1-8). The Modular Internal Distraction System (Howmedica Leibinger, Inc., Rutherford, NJ) was used for the gradual Le Fort III advancements. The average midface advancement obtained was 23 mm (range 15-30 mm), resulting in improved facial profile, normalized or improved dental occlusion, reduced exophthalmos, and cessation or a significant decrease in preoperative respiratory problems. The mean length of operation was 354 minutes (range 300-535 minutes), and the mean amount of perioperative blood transfusion needed was 1251 mL (range 450-1800 mL) or 46.0 mL/kg (range 8.2-121.4 mL/kg). Complications included subcutaneous infections inferolaterally to the eye (N = 3) and forehead (N = 1). One patient had worsening of her facial profile and underwent a subsequent fronto-orbital advancement. One patient developed a deviation of the nasal septum and needed a corrective rhinoplasty. One patient developed marked trismus and one needed reoperation and trimming of the anchoring titanium plate on the malar process. In one patient, the lacrimal sac was lacerated, leading to transient epiphora. In most patients, Le Fort III distraction led to a significant improvement in the facial profile. However, surgery is still a major undertaking, with several potential complications. In our hands, the rate of complications is not less than for monobloc advancement. Thus, the choice of operation method is not based on which method is the least risky but on which is best suited for the individual patient.

Monobloc and Midface Distraction Osteogenesis in Pediatric Patients with Severe Syndromal Craniosynostosis

We present 2 children with severe syndromal craniosynostosis who were in need of urgent midface advancement surgery due to recurrent ocular dislocations (Pfeiffer’s syndrome type II) or severe upper respiratory obstruction (Crouzon’s syndrome). They were operated using distraction osteogenesis, with gradual midface or monobloc advancements. In the Pfeiffer patient, a maxillary distraction of 25 mm achieved effective cessation of ocular dislocations, whereas a 23-mm monobloc advancement in the Crouzon patient achieved cessation of nocturnal arterial desaturations. No major postoperative complications were recorded. Distraction osteogenesis has become a versatile and safe technique that allows for large skeletal advancements.

Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients

OBJECT The objective of this study was to delineate the long-term results of surgical treatment of pediatric low-grade cerebellar astrocytoma. METHODS One hundred consecutive children and adolescents (0-19 years old) who underwent primary tumor resection for a low-grade cerebellar astrocytoma during the years 1980-2011 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. RESULTS Of the 100 patients, 61 children were in the 1st decade, and 39 were 10-19 years old. The male/female ratio was 1.13:1 (53 males, 47 females). No patients were lost to follow-up. There were no deaths in this series and all 100 patients are currently alive. In 29 patients, the follow-up duration was less than 10 years, in 37 it was between 10 and 19 years, and in 34 it was between 20 and 31 years. The Barthel Index was 100 (normal) in 97 patients, 90 in 2 patients, and 40 in the last patient. A total of 113 tumor resections were performed. Two patients underwent further tumor resection due to MRI-confirmed residual tumor demonstrated on the immediate postoperative MR image (obtained the day after the initial procedure). Furthermore, 9 children underwent repeat tumor resection after MRI-confirmed progressive tumor recurrence up to 10 years after the initial operation. Two of these patients also underwent a third resection, without subsequent radiation therapy, and have experienced 8 and 12 years of tumor-free follow-up thereafter, respectively. A total of 15% of the patients required treatment for persistent hydrocephalus. CONCLUSIONS Low-grade cerebellar astrocytoma is a surgical disease, in need of long-term follow-up, but with excellent long-term results. Nine percent of the children in this study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus.

Ependymoma in children and young adults (0-19 years): report of 25 consecutive cases.

Abstract The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given.

Long-term supratentorial brain structure and cognitive function following cerebellar tumour resections in childhood

The cerebellum is connected to extensive regions of the cerebrum, and cognitive deficits following cerebellar lesions may thus be related to disrupted cerebello-cerebral connectivity. Moreover, early cerebellar lesions could affect distal brain development, effectively inducing long-term changes in brain structure and cognitive function. Here, we characterize supratentorial brain structure and cognitive function in 20 adult patients treated for cerebellar tumours in childhood (mean age at surgery: 7.1 years) and 26 matched controls. Relative to controls, patients showed reduced cognitive function and increased grey matter density in bilateral cingulum, left orbitofrontal cortex and the left hippocampus. Within the patient group, increased grey matter density in these regions was associated with decreased performance on tests of processing speed and executive function. Further, diffusion tensor imaging revealed widespread alterations in white matter microstructure in patients. While current ventricle volume (an index of previous hydrocephalus severity it patients) was associated with grey matter density and white matter microstructure in patients, this could only partially account for the observed group differences in brain structure and cognitive function. In conclusion, our results show distal effects of cerebellar lesions on cerebral integrity and wiring, likely caused by a combination of neurodegenerative processes and perturbed neurodevelopment.