Spyros Sgouros

Identification and characterisation of childhood cerebellar tumours by in vivo proton MRS.

1H MRS has great potential for the clinical investigation of childhood brain tumours, but the low incidence in, and difficulties of performing trials on, children have hampered progress in this area. Most studies have used a long‐TE, thus limiting the metabolite information obtained, and multivariate analysis has been largely unexplored. Thirty‐five children with untreated cerebellar tumours (18 medulloblastomas, 12 pilocytic astrocytomas and five ependymomas) were investigated using a single‐voxel short‐TE PRESS sequence on a 1.5 T scanner. Spectra were analysed using LCModelTM to yield metabolite profiles, and key metabolite assignments were verified by comparison with high‐resolution magic‐angle‐spinning NMR of representative tumour biopsy samples. In addition to univariate metabolite comparisons, the use of multivariate classifiers was investigated. Principal component analysis was used for dimension reduction, and linear discriminant analysis was used for variable selection and classification. A bootstrap cross‐validation method suitable for estimating the true performance of classifiers in small datasets was used. The discriminant function coefficients were stable and showed that medulloblastomas were characterised by high taurine, phosphocholine and glutamate and low glutamine, astrocytomas were distinguished by low creatine and high N‐acetylaspartate, and ependymomas were differentiated by high myo‐inositol and glycerophosphocholine. The same metabolite features were seen in NMR spectra of ex vivo samples. Successful classification was achieved for glial‐cell (astrocytoma + ependymoma) versus non‐glial‐cell (medulloblastoma) tumours, with a bootstrap 0.632 + error, eB.632+, of 5.3%. For astrocytoma vs medulloblastoma and astrocytoma vs medulloblastoma vs ependymoma classification, the eB.632+ was 6.9% and 7.1%, respectively. The study showed that 1H MRS detects key differences in the metabolite profiles for the main types of childhood cerebellar tumours and that discriminant analysis of metabolite profiles is a promising tool for classification. The findings warrant confirmation by larger multi‐centre studies. Copyright

Spinal Sagittal Malalignment following Surgery for Primary Intramedullary Tumours in Children

Background/Objective: As prior studies analysed predictive factors for various post-laminectomy spinal deformities in mixed spinal regions, age groups or pathologies, their validity and conclusions were unclear. The objective of this study was to determine predictive factors for worsened cervical or thoracic spinal sagittal alignment following laminectomy or laminotomy for primary intramedullary spinal cord tumours in children. Methods: In this retrospective study, patients treated between 1980 and 1998 were reviewed. Changes in spinal alignment at the last follow-up compared to the pre-operative state were studied. Factors analysed were age, pre-operative spinal alignment, procedure types (laminectomy or laminoplasty), number of laminae operated, surgery of C2 or T1 laminae, histological grade, presence of post-operative neurological deficit and post-operative radiotherapy. Results: There were 27 patients. The mean age was 5.6 years (range 1.3–14.0 years), and the mean duration of follow-up was 3.7 years (range 0.075–9.9 years). In the cervical-cervicothoracic surgical group (n = 12), alignment worsened post-operatively in 3 patients. The number of laminae operated upon had a statistically significant impact on the development of post-operative kyphosis (p = 0.07). In the thoracic-thoracolumbar surgical group (n = 15), alignment worsened in 9 patients. Procedure types were statistically significantly different, with laminectomy associated with an increased risk of post-operative kyphosis (p = 0.01). All 5 patients who had spinal fusion for worsened post-operative alignment were in the thoracic-thoracolumbar group; no patients in the cervical-cervicothoracic group required spinal fusion (p = 0.047). Other predictive factors did not reach statistical significance (p > 0.05). Conclusions: Worsened spinal sagittal alignment following laminectomy or laminoplasty and the need for spinal fusion is more common in the thoracic-thoracolumbar region than in the cervical-cervicothoracic region. In the cervical-cervicothoracic region, operation on a greater number of laminae tends to increase the risk of worsened alignment. In the thoracic-thoracolumbar region, laminectomy is associated with worsened alignment, while laminoplasty reduces this risk; also, pre-operative kyphotic deformity tends to increase the risk of worsened alignment post-operatively.

Posterior skull surgery in craniosynostosis

In 1984, two young infants with unusual “clover-leaf” patterns of skull deformity were treated by posterior skull-releasing surgery that dramatically improved their overall skull shape, to the extent that further operative intervention was not required. This focused our attention on the posterior skull and its role in craniosynostosis. In cases of multi-suture craniosynostosis and craniofacial syndromes severely raised intracranial pressure is frequent, demanding early surgery. One of the problems identified with such surgery undertaken before 6 months of age is recurrent craniosynostosis needing later re-operation. This occurred in 15 (5%) of 275 patients treated between 1978 and 1994. Since 1986, in the presence of significantly raised intracranial pressure it has been our policy to do an initial posterior skull release or decompression. This takes the pressure of the growing brain away from the orbits, allowing us to defer fronto-orbital advancement until the age of 12 months or later. Three patients managed in this way completely avoided anterior surgery, while in another 9 patients re-operation for recurrent anterior deformity has not been required. The exception to this policy has been the presence of severe exorbitism posing a threat to vision. Under these circumstances early fronto-orbital advancement is mandatory, and an additional posterior skull release may be helpful later. Debate continues especially on the management of unilateral lambdoid synostosis. The recent increase in positional posterior plagiocephaly, possibly related to supine nursing of newborns, has emphasised the need to differentiate between a fixed deformity, which might require surgical correction, and positional moulding of the occiput, which improves spontaneously. This paper reports our experience with 22 patients treated by posterior skull surgery, either alone or as an additional procedure, which we believe has a definitive role in the management of craniosynostosis.

Skull base growth in childhood

While studying skull base changes in craniosynostosis, it became apparent that there is a lack of reference studies quantifying the changes of three-dimensional (3D) parameters of the normal skull base throughout childhood. Using advanced 3D visualisation techniques, 34 points of the skull base were identified on MRI scans of 66 normal children, aged 1 month to 15 years. Several distances and angles between the various landmarks were measured in an attempt to quantify the growth of skull fossae with age. Two main growth periods were observed: before and after the first 5 years of life. Most change occurred in the first period. Anatomical regional differences were identified between the two sexes. During the first 5 years of life, the anterior fossa showed rapid growth rate with respect to its anterior projection in males, whereas in the females there was a more concentric growth pattern. The body of the sphenoid bone and the middle fossa showed a rapid growth rate in both sexes which was greater in the females. The posterior fossa showed a concentric pattern of growth in both sexes with a greater growth rate in the females. These findings provide new insight into the pattern of growth of the various parts of the skull base and can be used for comparative study of deformities that affect such growth.

Extracellular glutamine to glutamate ratio may predict outcome in the injured brain: a clinical microdialysis study in children

The amino acid content of hourly microdialysis samples from nine severely head-injured children was examined. Of particular interest was the measurement of the excitatory amino acid glutamate, as high levels of this substance, which are associated with the excitotoxicity cascade, have been linked to high intracranial pressure and poor outcome in a similar study in adults. Interpretation of these data is complicated by many clinical and methodological factors and these are discussed in relation to the findings. Our findings from this pilot study in children confirm the associations between glutamate levels, intracranial pressure and outcome, but fail to corroborate the correlation between excitatory and structural amino acid levels seen in adult patients, that was interpreted as evidence of non-specific leakage of amino acids through damaged cell membranes. In addition, we have shown that the role of glutamine in glutamate homeostasis is an important consideration and that estimation of the extracellular glutamine/glutamate ratio may have some prognostic value in head trauma cases as there is evidence of links to clinical outcome.

The international infant hydrocephalus study: concept and rational

IntroductionDuring the recent meetings of the International Study Group on Neuroendoscopy and the International Society for Pediatric Neurosurgery, the consensus view emerged that there is a need to assess the value and efficacy of neuroendoscopic procedures against shunting in a scientific manner, to resolve long-lasting debates on the subject.Material and methodsA prospective randomized, controlled trial of endoscopic third ventriculostomy vs shunting in children presenting under the age of 2 years with pure aqueduct stenosis is been proposed and organized (the International Infant Hydrocephalus Study, IIHS). The participating surgeons must adhere to the philosophy of randomization and be suitably experienced in endoscopic techniques in infants. The primary outcome of the trial will be the overall health-related quality of life of these children at 5 years of age. Hence, the study is focusing on the effect of surgery on neurodevelopment, rather than the less important issue of shunt or stoma survival, that has been debated extensively with no conclusion so far. Intention-to-treat analysis will be performed according to the first surgery. Secondary outcomes such as complication and reoperation rate, total hospitalization time and cost, need for repeat imaging, and others will be analyzed as well.ResultsPure aqueduct stenosis is relatively rare, making recruitment problematic, but has been chosen to avoid other confounding factors that could influence outcome. More than 25 centers worldwide have committed already to patient recruitment to the study. It is anticipated that recruitment will last for 2 years, aiming for 91 patients per arm. The study has started recruiting patients already in some countries.ConclusionIt is hoped that the trial will not only provide answers to unsettled debates on the value of neuroendoscopy but also create a network of collaborating pediatric neurosurgeons for future initiatives.

The Influence of Hair Shave on the Infection Rate in Neurosurgery

Objective: To investigate whether not shaving hair in neurosurgical operations carries an increased infection rate. Methods: Taking advantage of different practices among neurosurgeons in a single institution, we embarked upon a prospective non-randomised study of 100 consecutive neurosurgical procedures involving 90 paediatric patients aged 7 days to 16.8 years. The patients were split into two groups (‘hair shave’ and ‘no hair shave’). The differences with respect to wound complications, positive microbiology on wound culture swabs and wound infection rates were analysed. Other factors considered were the cleansing solution, prophylactic antibiotic regime, duration of the operation, the surgeon’s experience and the patient’s age. Results: The only complications observed were 4 incidences of wound dehiscence (2 in the hair shave and 2 in the no hair shave group) and 3 shunt infections (2 in the hair shave and 1 in the no hair shave group). We did not find any significant difference between the two arms for any of the factors assessed. Age was a significant factor in shunt infection, as all shunt infections were seen in patients aged less than 6 months, regardless of whether the hair was shaved or not (p = 0.024, Fisher’s exact test). Conclusion: This study confirms our clinical experience that no hair shave is a good alternative to the traditional hair shaving approach, allowing patients to enjoy the psychological benefits of undisturbed body image while recovering from major surgery.

Skull base growth in children with Chiari malformation Type I

OBJECT The goal of this study was to establish whether children with Chiari malformation Type I (CM-I) have abnormal skull base geometry. METHODS Distances and angles between skull base landmarks were measured on preoperative magnetic resonance images obtained in 30 children (age range 36-204 months) with symptomatic isolated CM-I; 16 of them (53%) had syringomyelia. Comparisons were made with 42 children of similar age who comprised the control group by using one-way analysis of variance. RESULTS The angle formed by the crista galli (CG), dorsum sellae (DS), and foramen magnum (FM) was larger than normal in individuals with CM-I than in those without (145 degrees in patients with CM-I but no syringomyelia and 151 degrees in those with CM-I and syringomyelia compared with 135 degrees in controls; p = 0.000). The angle formed by the left internal auditory meatus (IAM), FM, and right IAM was also larger than normal in the patients (122 degrees in patients with CM-I but no syringomyelia and 123 degrees in those with CM-I and syringomyelia compared with 110 degrees in controls; p = 0.001). The angle formed by the anterior clinoid process (ACP), CG, and right ACP was smaller than normal (29 degrees in all patients with CM-I compared with 34 degrees in controls; p = 0.000). The distance between the two IAMs was longer than normal (75 mm in patients with CM-I but no syringomyelia and 63 mm in those with CM-I and syringomyelia compared with 58 mm in controls; p = 0.000). The distance between the two ACPs was shorter than normal in the syringomyelia group (31 mm in patients with CM-I but no syringomyelia and 27 mm in those with CM-I and syrinx compared with 32 mm in controls; p = 0.001). Within the group of patients with CM-I, the DS-FM and left ACP-right ACP distances were smaller in the syringomyelia group (p = 0.009 and p = 0.037, respectively). CONCLUSIONS Children with CM-I have abnormal geometrical measurements of their entire skull base, not only the posterior fossa, irrespective of presence of syringomyelia. This may indicate a mesodermal defect as a possible cause of the malformation.

Spinal teratoma : is there a place for adjuvant treatment? Two cases and a review of the literature

Spinal teratomas are rare intradural spinal tumours, commonly of benign histological profile. The main treatment remains surgical excision which often is incomplete as the tumour is frequently intimately related to surrounding nerve roots and adjacent spinal cord. The value of adjuvant treatment in the form of radiotherapy has not been clearly identified. We report two patients with spinal teratomas in the lower thoracic and conus region, who were treated with surgical excision and did not receive radiotherapy. One of the tumours recurred at 38 months following surgical excision and required a second operation. We review in addition another 20 patients reported in the literature with such tumours. With a mean follow-up of 25 months a local recurrence rate of 10% was observed, the same in both total and subtotal excision groups. No deaths were reported. Analysis of cumulative survival from surgery to treatment failure demonstrated that recurrence occurs late, verifying a slow biological progression of this tumour type. Although no reliable information of the effect of radiotherapy can be obtained, it is difficult to see how radiotherapy could have an impact on such a slow growing tumour. Initial treatment of choice remains surgical excision. If the teratoma shows any malignant histological features or germ cell elements radiotherapy should be employed after surgical excision, even if apparently totally excised. In the presence of benign histology it would seem appropriate to avoid radiotherapy after initial surgery. In case of tumour recurrence or progression to explore the possibility of further surgery first, before considering radiotherapy which even then may have doubtful efficacy.Spinal teratomas are rare intradural spinal tumours, commonly of benign histological profile. The main treatment remains surgical excision which often is incomplete as the tumour is frequently intimately related to surrounding nerve roots and adjacent spinal cord. The value of adjuvant treatment in the form of radiotherapy has not been clearly identified. We report two patients with spinal teratomas in the lower thoracic and conus region, who were treated with surgical excision and did not receive radiotherapy. One of the tumours recurred at 38 months following surgical excision and required a second operation.We review in addition another 20 patients reported in the literature with such tumours.With a mean follow-up of 25 months a local recurrence rate of 10% was observed, the same in both total and subtotal excision groups. No deaths were reported. Analysis of cumulative survival from surgery to treatment failure demonstrated that recurrence occurs late, verifying a slow biological progression of this tumour type. Although no reliable information of the effect of radiotherapy can be obtained, it is difficult to see how radiotherapy could have an impact on such a slow growing tumour. Initial treatment of choice remains surgical excision. If the teratoma shows any malignant histological features or germ cell elements radiotherapy should be employed after surgical excision, even if apparently totally excised. In the presence of benign histology it would seem appropriate to avoid radiotherapy after initial surgery. In case of tumour recurrence or progression to explore the possibility of further surgery first, before considering radiotherapy which even then may have doubtful efficacy.

Skull Base Growth in Craniosynostosis

Although considerable scientific work has been published on the role of the skull base in craniosynostosis, the changes with age throughout childhood have not been fully outlined. The realisation that little attention has been paid to the posterior skull in craniosynostosis, resulted in renewed interest in skull base growth. The availability of computer-based image analysis provides a new accurate method of study in three dimensions. Using three-dimensional visualisation techniques, 34 points of the skull base were identified on CT scans of 50 children with craniosynostosis of various types, aged from 1 month to 5 years. Several distances and angles between the various landmarks were measured in an attempt to quantify the growth of skull fossae with age. Comparisons were made with normal controls. In children with craniosynostosis, the anterior fossa was overdeveloped in the males, whereas in the females remained underdeveloped throughout the first 2 years of life. The body of the sphenoid showed moderate underdevelopment in the first 2 years in both sexes, the effect being more prominent in the males. The middle fossae showed overdevelopment in both sexes in the first 2 years of life. The posterior fossa was underdeveloped in both sexes in the first 2 years of life, the effect being more prominent in the females. Craniosynostosis seems to affect both sexes to a similar degree, but there are regional differences in the growth pattern. Better understanding of the normal growth pattern of the skull base and the effect of craniosynostosis upon it may assist our approach to surgical treatment and in particular the role of anterior and posterior skull expansive surgery.