Publications by authors named "Paolo Frassanito"

78 Publications

Managing children with brain tumors during the COVID-19 era: Don't stop the care!

Comput Struct Biotechnol J 2021 12;19:705-709. Epub 2021 Jan 12.

Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy.

The COVID-19 pandemic has substantially stressed health care systems globally, subsequently reducing cancer care services and delaying treatments. Pediatric populations infected by COVID-19 have shown mild clinical symptoms compared to adults, perhaps due to decreased susceptibility. Several scientific societies and governments have released information on the management of patients with cancer, wherein they warn against exposure to SARS-CoV-2 infection and suggest continuing treatment. To determine the best diagnostic and therapeutic approach, multidisciplinary tumor boards should convene regularly, including through conference calls and telematics platforms. A prompt diagnostic workup may reduce children's suffering and prevent loss of confidence in the health care system among parents. Moreover, ensuring adequate support and information regarding measures for preventing SARS-CoV-2 infection in pediatric patients and their families is essential for avoiding panic and excessive stress, allowing early reporting of any suspected symptoms of cancer and, in turn, facilitating early diagnosis and prompt modulation of treatment.
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http://dx.doi.org/10.1016/j.csbj.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817528PMC
January 2021

Reply to letter to the editor regarding "Diagnosis and management of cerebral venous sinus thrombosis in children: a single-center retrospective analysis".

Childs Nerv Syst 2021 Feb 6;37(2):357-358. Epub 2021 Jan 6.

Dipartimento di Neurochirurgia Infantile, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

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http://dx.doi.org/10.1007/s00381-020-05005-7DOI Listing
February 2021

Diagnosis and management of cerebral venous sinus thrombosis in children: a single-center retrospective analysis.

Childs Nerv Syst 2021 Jan 6;37(1):153-160. Epub 2020 Nov 6.

Dipartimento di Pediatria, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.

Purpose: Cerebral venous thrombosis (CVT) is a rare disease in children, characterized by partial or total occlusion of blood flow in the cerebral venous system. The aim of this study is to describe clinical presentation, neuroimaging features, therapeutic management, and outcome of children with CVT.

Methods: We retrospectively analyzed the data, including clinical manifestations, laboratory data, neurological findings, and treatment of children with radiologically confirmed CVT, admitted between January 2010 and March 2020 to our hospital. Cases of CVT complicating brain surgery were excluded.

Results: We enrolled 24 children with CVT. Infection was the main etiology (58.3%), followed by trauma in 16.7% of cases. In the remaining 25% of cases, the cause was identified only in one patient presenting a thrombophilic factor. The most frequent site of thrombosis was the superficial venous system (86.8%), with multiple localizations disclosed in 79% of patients. All children received anticoagulant therapy with low molecular weight heparin (LMWH). One patient died for systemic complications of an underlying disease. No patient developed hemorrhagic events during the therapy, lasting from 35 to 360 days (mean 86 days). In all but one surviving patients (22 out of 24), recanalization of the sinus was observed at AngioMRI performed during follow-up. No neurological complications of CVT were recorded (mean follow-up: 1.5 year).

Conclusions: CVT may present with subtle and unspecific clinical manifestations in children. High level of suspicion should be kept in trauma and sinusitis. Anticoagulation treatment is safe and effective and should be promptly started to improve outcome.
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http://dx.doi.org/10.1007/s00381-020-04958-zDOI Listing
January 2021

Current trends in the management of subependymal giant cell astrocytomas in tuberous sclerosis.

Childs Nerv Syst 2020 10 25;36(10):2527-2536. Epub 2020 Sep 25.

Pediatric Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy.

Introduction: The management of subependymal giant cells astrocytomas (SEGAs) has been traditionally represented by surgical treatment through an open craniotomic approach. Though open surgery still represents a major option in the management of this kind of tumors, the introduction of mTOR inhibitors in the clinical practice, technological advances in neuroendoscopy and the more recent use of laser interstitial therapy have significantly enlarged the range of available management opportunities.

Methods: A thorough review of the literature has been performed. Accordingly, current views in open surgical treatment, medical therapy, endoscopic tumor removal and new trends (such as laser interstitial thermal therapy) are discussed.

Results: The risk of significant neurological morbidity (5-50%) complicating open surgery has been for a long time representing a main drawback in the management of SEGAs. More recent series report a significant reduction of morbidity and mortality. The mTOR inhibitors have demonstrated efficacy in both warranting a tumor reduction by up to 60% of the tumor size and helping the control of seizures. However, the reported rate of side effects is as high as 30% and tumor recurrence is a documented occurrence at the time of mTOR inhibitor discontinuation. Endoscopic tumor removal has been more extensively considered an option due to the acquisition of new tools. Limits are still represented by tumor size (< 3 cm) and broad attachment of the tumor to the basal ganglia. Laser interstitial thermal therapy (LITT) is the more recently considered option. Though promising, only short follow-up is available so far, while data on medium- and long-term results of this treatment are completely lacking to date.

Conclusions: Surgical treatment remains a mainstay of the management of SEGAs. The indication for an open craniotomic approach should be balanced with an endoscopic tumor removal or LITT according to patient conditions, presence or not of an active hydrocephalus and extension of the attachment of the tumor to the basal ganglia. The mTOR inhibitors do have a definite role both as primary and as adjuvant treatment, but consistent limitations are represented up to now by a not negligible rate of complications and the uncertainties related to the possibility of tumor recurrence once the medical treatment is discontinued.
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http://dx.doi.org/10.1007/s00381-020-04889-9DOI Listing
October 2020

Neurocutaneous Melanosis in Infancy: Always a Dismal Prognosis?

Turk Neurosurg 2020 ;30(4):476-482

Fondazione Policlinico Gemelli IRCSS, Department of Pediatric Neurosurgery, Rome, Italy.

Aim: To analyze the current literature on neurocutaneous melanosis (NCM), as well as, our cases, in order to better define the prognosis and the presence of risk factors affecting it, thus, offering better information to the parents.

Material And Methods: Two cases observed at the Pediatric Neurosurgery Unit of the Catholic University Medical School in Rome are described. Both of them had cutaneous stigmata and cerebral MR evidence of intracranial melanin deposits. These two children showed a very different clinical course.

Results: The present study enlighten the differences among the two cases and review the literature on the subject, with the attempt to understand which are clinical and disease related factors that might influence the prognosis.

Conclusion: Beside malignant features of cutaneous melanotic lesions, the presence of hydrocephalus at diagnosis and the early appearance of clinical symptoms, when appearing contemporarily, are predicting the rapid progression of the disease and a worse prognosis.
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http://dx.doi.org/10.5137/1019-5149.JTN.27908-19.3DOI Listing
November 2020

Gelfoam Migration: A Potential Cause of Recurrent Hydrocephalus.

World Neurosurg 2020 10 4;142:212-217. Epub 2020 Jul 4.

Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:

Background: Gelfoam is a simple and effective hemostatic agent that is used to seal brain corticotomies or skull burr holes. Owing to its low cost, it is one of the most widely used tools in neurosurgical daily practice. However, migration of Gelfoam fragments can cause occlusion of endoscopic third ventriculostomy (ETV) or shunt, leading to hydrocephalus recurrence.

Case Description: Two cases of Gelfoam migration causing recurrent hydrocephalus are presented: a 12-year-old girl who underwent surgery for posterior fossa tumor removal and ETV for associated hydrocephalus, where a portion of Gelfoam (used to seal the burr hole) migrated up to close the ETV, and a preterm 8-month-old boy who was treated by neuroendoscopic brain lavage and afterward by ventriculoperitoneal shunt for posthemorrhagic hydrocephalus, where all the Gelfoam used to close the corticotomy migrated into the lateral ventricle, thus reopening the corticotomy and releasing small fragments that ultimately obstructed the shunt. A new endoscopic procedure was required in both patients (the second patient also required a shunt revision).

Conclusions: Review of the pertinent literature discloses other complications of Gelfoam migration (e.g., mass effect, granulomatous reaction) as well as other causes of uncommon ETV/shunt obstruction. Nonetheless, Gelfoam will remain an indispensable tool for neurosurgeons. The present report emphasizes the importance of its correct use to avoid complications.
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http://dx.doi.org/10.1016/j.wneu.2020.06.214DOI Listing
October 2020

GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis.

Int J Mol Sci 2020 Jun 19;21(12). Epub 2020 Jun 19.

Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients' calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.
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http://dx.doi.org/10.3390/ijms21124356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352200PMC
June 2020

Securing CSF catheters to the skin: from sutures and bolt system to subcutaneous anchoring device towards zero complications.

Childs Nerv Syst 2020 Nov 17;36(11):2749-2755. Epub 2020 Jun 17.

Pediatric Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.

Introduction: Securing the catheter to the skin either with sutures or staples and to the skull with bolt system still represents the most common options in the management of CSF external drainage. However, these options bear an unavoidable risk of complications. This problem is common to vascular accesses and has been successfully overcome with the introduction of device for subcutaneous anchoring (SecurAcath®, Interrad Medical, Inc., Plymouth, Minnesota), which has rapidly become the standard of care in this field.

Methods: We report our experience with the use of SecurAcath® to secure CSF drainage, either ventricular or spinal. Results were compared with literature data.

Results: Since 2015, SecurAcath® was used in 209 patients (mean age 7 years) to secure 195 external cranial catheters (either ventricular or subdural or intralesional) and 16 spinal drainages. Indwell time ranged from 5 to 30 days. No complication related to the use of the device was observed. In particular, there was no case of dislocation or accidental pullout of the catheter. Rate of infection, or superinfection in case of ventricular catheter implanted for CSF infection, was null.

Conclusions: SecurAcath® is a safe and effective device to secure CSF external catheters, with several relevant advantages, including easy placement and maintenance. Moreover, it may stay in place for the whole duration of the catheter without any skin tissue trauma and allows a complete antisepsis of the exit site, thus reducing local skin complications. This factor has significant impact on the reduction of infection rate of external CSF catheters.
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http://dx.doi.org/10.1007/s00381-020-04737-wDOI Listing
November 2020

A Rare Case of Postinfectious Moyamoya Syndrome: Case Report and Review of the Literature.

World Neurosurg 2020 08 17;140:213-218. Epub 2020 May 17.

Radiology and Neuroradiology, Department of Diagnostic for Images, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: Postinfectious Moyamoya syndrome (MMS) is a rare vasculopathy that can follow meningitis. Only 9 cases of MMS after meningitis have been reported in the literature. We present a unique case of MMS after meningitis caused by Aspergillus fumigatus and Escherichia coli and review all cases of MMS postmeningitis in the literature.

Case Description: A 41-year-old man was admitted to our emergency department for sudden hypoesthesia in the left arm and an intense headache not responsive to drugs. Computed tomography scan and magnetic resonance imaging showed acute ischemic lesions in the right centrum semiovale associated with bilateral chronic watershed cerebral ischemic lesions. The cerebral digital subtraction angiography documented a typical Moyamoya pattern. In anamnesis, the patient suffered from meningitis caused by A. fumigatus and E. coli infection after neurosurgery for subependymoma of the fourth ventricle 2 years before. Laboratory tests, clinical investigation, and imaging ruled out any other cause of vasculopathy and led to the final diagnosis of postinfectious MMS. The patient started medical therapy with oral acetyl salicylic acid, verapamil, and prednisone while surgical approach was excluded in the first instance.

Conclusions: Physicians should be aware of an uncommon but severe complication of meningitis such as MMS, even several years after the infection. Neuroimaging is essential for the diagnosis and to exclude other causes of neurologic symptoms in these patients.
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http://dx.doi.org/10.1016/j.wneu.2020.05.082DOI Listing
August 2020

The scalp block for postoperative pain control in craniosynostosis surgery: a case control study.

Childs Nerv Syst 2020 Dec 17;36(12):3063-3070. Epub 2020 May 17.

Anesthesia and Intensive care, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy.

Purpose: Postoperative analgesia after corrective surgery of pediatric craniosynostosis is crucial in terms of short- and long-term outcomes. The objective of this observational study was to evaluate the effectiveness of an analgesic technique based on the scalp block versus traditional pharmacological approach.

Methods: Thirteen patients, aged between 3 months and 2 years, undergoing surgical correction of craniosynostosis, received scalp nerve block before awakening (scalp block group). This group of patients was compared to a second group of 13 patients, retrieved from our database, treated with the traditional pharmacological approach (control group). Pain scores, need of rescue therapy, resumption of oral nutrition, degree of parent satisfaction at discharge, and length of stay in the Pediatric Intensive Care Unit (PICU) and in the hospital were compared between the two groups.

Results: Objective Pain Score values were significantly lower in patients treated with scalp block at 30 min and at 8 h after extubation. The number of pharmacological interventions for the treatment of pain in PICU was significantly higher in Control group. Children in Scalp block group started earlier oral feeding than in Control group, both for clear fluids and milk. Length of stay in PICU was longer in Scalp block group than in Control group, though the difference between the mean data in the two groups is about 3 . This difference does not seem significant from a clinical standpoint, since it seems more related to logistic issues (e.g., availability of bed in the Pediatric Neurosurgery Unit, presence of a parent), rather than clinical problems contraindicating the discharge from PICU. Indeed, the overall hospital length of stay was similar between the two groups.

Conclusion: Scalp nerve block was effective for immediate postoperative pain control in patients younger than 2 years who underwent cranioplasty for craniosynostosis. The best pain control compared to conventional therapy allowed to limit the need for rescue analgesics in PICU and an earlier recovery time. ClinicalTrials.gov Identification: NCT04133467.
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http://dx.doi.org/10.1007/s00381-020-04661-zDOI Listing
December 2020

Role of susceptibility-weighted imaging and intratumoral susceptibility signals in grading and differentiating pediatric brain tumors at 1.5 T: a preliminary study.

Neuroradiology 2020 Jun 6;62(6):705-713. Epub 2020 Mar 6.

UOC Radiodiagnostica e Neuroradiologia, Dipartimento di Diagnostica per Immagini, Radioterapia, Oncologia ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Purpose: Susceptibility-weighted imaging (SWI) is useful for glioma grading and discriminating between brain tumor categories in adults, but its diagnostic value for pediatric brain tumors is unclear. Here we evaluated the usefulness of SWI for pediatric tumor grading and differentiation by assessing intratumoral susceptibility signal intensity (ITSS).

Methods: We retrospectively enrolled 96 children with histopathologically diagnosed brain tumors, who underwent routine brain MRI exam with SWI (1.5 T scanner). Each tumor was assigned an ITSS score by a radiology resident and an experienced neuroradiologist, and subsequently by consensus. Statistical analyses were performed to differentiate between low-grade (LG) and high-grade (HG) tumors, histological categories, and tumor locations. Inter-reader agreement was assessed using Cohen's kappa (κ).

Results: The interobserver agreement was 0.844 (0.953 between first reader and consensus, and 0.890 between second reader and consensus). Among all tumors, we found a statistically significant difference between LG and HG for ITSS scores of 0 and 2 (p = 0.002). This correlation was weaker among astrocytomas alone, and became significant when considering only off-midline astrocytomas (p = 0.05). Scores of 0 and 2 were a strong discriminating factor (p = 0.001) for astrocytomas (score 0) and for embryonal, choroid plexus, germ-cell, pineal, and ependymoma tumors (score 2). No medulloblastoma showed a score of 0.

Conclusions: Our preliminary ITTS results in pediatric brain tumors somewhat differed from those obtained in adult populations. These findings highlight the potential valuable role of ITSS for tumor grading and discriminating between some tumor categories in the pediatric population.
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http://dx.doi.org/10.1007/s00234-020-02386-zDOI Listing
June 2020

In response to the letter to the editor related to "Management and Prevention of Cranioplasty Infections" by Shay T, Mitchell KA, Gordon CR Recognizing a problem is the first step in fixing it.

Childs Nerv Syst 2019 12 24;35(12):2251-2252. Epub 2019 Oct 24.

Infectious Diseases Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1007/s00381-019-04388-6DOI Listing
December 2019

Acute presentations of intradural lipomas: case reports and a review of the literature.

BMC Neurol 2019 Aug 8;19(1):189. Epub 2019 Aug 8.

Pediatric Neurosurgery - Neurosurgery Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: Lumbosacral lipomas (LLs) may remain asymptomatic or lead to progressive neurological deterioration. However, sudden neurological deterioration is a rare and severe event. Herein, we report rare occurrences of sudden clinical deterioration in two previously asymptomatic children harbouring intradural LLs without dermal sinus tracts or signs of occult dysraphism. A review of the pertinent literature is also included.

Case Presentation: One child exhibited acute deterioration because of an epidural abscess associated with a filar lipoma without a sinus tract (probably caused by haematogenous spreading from a respiratory tract multiple infection), and the other child exhibited acute deterioration because of a very large, holocord syringomyelia-like cyst associated with a small conus lipoma. Both patients were 4 years old. In case #2, a previously undetected, severe tethered cord (conus at the S3-S4 level) was also present. A complete recovery was attained after an urgent surgical operation in both cases (in addition to targeted antibiotic therapy in case #1). All cases of deterioration in the literature were caused by abscess formation in dermal sinus tracts.

Conclusions: Prophylactic surgery may be indicated even in asymptomatic children that have tethered cord and surgically favourable LLs (small dorsal and filar LLs), especially if the conditions are associated with progressive syringomyelia. Similarly, intradural dermal sinus tracts should be regarded as surgery-indicated, even if the conus is in its normal position and the patient is asymptomatic because there is a consistent risk of severe, infection-related complications. Finally, asymptomatic patients with filar LLs and a normally located conus can be candidates for surgery or an accurate clinical and radiological follow-up.
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http://dx.doi.org/10.1186/s12883-019-1413-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688213PMC
August 2019

Chiari type I and hydrocephalus.

Childs Nerv Syst 2019 10 21;35(10):1701-1709. Epub 2019 Jun 21.

Fondazione Policlinico Gemelli IRCCS, Neurochirurgia Infantile, Roma, Italy.

Purpose: The association between Chiari type I malformation (CIM) and hydrocephalus raises a great interest because of the still unclear pathogenesis and the management implications. The goal of this paper is to review the theories on the cause-effect mechanisms of such a relationship and to analyze the results of the management of this condition.

Methods: A review of the literature has been performed, focusing on the articles specifically addressing the problem of CIM and hydrocephalus and on the series reporting about its treatment. Also, the personal authors' experience is briefly discussed.

Results: As far as the pathogenesis is concerned, it seems clear that raised intracranial pressure due to hydrocephalus can cause a transient and reversible tonsillar caudal ectopia ("pressure from above" hypothesis), which is something different from CIM. A "complex" hypothesis, on the other hand, can explain the occurrence of hydrocephalus and CIM because of the venous engorgement resulting from the hypoplasia of the posterior cranial fossa (PCF) and the occlusion of the jugular foramina, leading to cerebellar edema (CIM) and CSF hypo-resorption (hydrocephalus). Nevertheless, such a mechanism can be advocated only in a minority of cases (syndromic craniosynostosis). In non-syndromic CIM subjects, the presence of hydrocephalus could be explained by an occlusion of the basal CSF pathways, which would occur completely in a minority of cases (only 7-10% of CIM patients show hydrocephalus) while it would be partial in the remaining cases (no hydrocephalus). This hypothesis still needs to be demonstrated. As far as the management is concerned, the strategy to treat the hydrocephalus first is commonly accepted. Because of the "obstructive" origin of CIM-related hydrocephalus, the use of endoscopic third ventriculostomy (ETV) is straightforward. Actually, the analysis of the literature, concerning 63 cases reported so far, reveals very high success rates of ETV in treating hydrocephalus (90.5%), CIM (78.5%), and syringomyelia symptoms (76%) as well as in giving a radiological improvement of both CIM (74%) and syringomyelia (89%). The failures of ETV were not attributable to CIM or syringomyelia. Only 11% of cases required PCF decompression after ETV.

Conclusions: The association between CIM and hydrocephalus probably results from different, multifactorial, and not yet completely understood mechanisms, which place the affected patients in a peculiar subgroup among those constituting the heterogeneous CIM population. ETV is confirmed as the best first approach for this subset of patients.
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http://dx.doi.org/10.1007/s00381-019-04245-6DOI Listing
October 2019

Management and prevention of cranioplasty infections.

Childs Nerv Syst 2019 09 20;35(9):1499-1506. Epub 2019 Jun 20.

Infectious Diseases Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: Infection may complicate the outcome of cranial repair with significant additional morbidity, related to hospitalization, surgery and long antibiotic therapy, that may become even dramatic in case of multi-resistant germs and in particular in the paediatric population. Additionally, the economic costs for the health system are obvious. Moreover, surgical decisions concerning the timing of cranioplasty and choice of the material may be strongly affected by the risk of infection. Despite, management and prevention of cranioplasty infections are not systematically treated through the literature so far.

Methods: We reviewed pertinent literature dealing with cranioplasty infection starting from the diagnosis to treatment options, namely conservative versus surgical ones. Our institutional bundle, specific to the paediatric population, is also presented. This approach aims to significantly reduce the risk of infection in first-line cranioplasty and redo cranioplasty after previous infection.

Conclusions: A thorough knowledge and understanding of risk factors may lead to surgical strategies and bundles, aiming to reduce infectious complications of cranioplasty. Finally, innovation in materials used for cranial repair should also aim to enhance the antimicrobial properties of these inert materials.
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http://dx.doi.org/10.1007/s00381-019-04251-8DOI Listing
September 2019

Cerebellar mutism: the predictive role of preoperative language evaluation.

Childs Nerv Syst 2020 06 14;36(6):1153-1157. Epub 2019 Jun 14.

Pediatric Neurosurgery, Institute of Neurosurgery and Institute of Infantile Neuropsychiatry, Fondazione Policlinico Gemelli IRCSS, Rome, Italy.

Background: The association between preoperative language impairment and development of cerebellar mutism after surgical treatment of posterior fossa tumors has gained increasing interest in recent years based on the concept that both local compression/infiltration of the infratentorial periventricular anatomical structures involved in speech and language, as well as an increased distraction of supratentorial periventricular anatomical structures, due to an associated hydrocephalus, involved in the coordination of speech circuits, might lead to the subclinical presence of language disturbances already at diagnosis, predicting the development of a cerebellar mutism syndrome after tumor removal.

Methods: A thorough review of the literature on the subject has been performed, together with a review of our institutional experience reporting the related long-term (10 years) results.

Results And Conclusions: According to our institutional experience, 20/70 (28.5%) children presented preoperative language impairment and developed cerebellar mutism after surgery. A residual impairment persists in 75% of the cases at a follow-up of 2 years, and in 50% of the cases at 10 years, a finding which actually depicts cerebellar mutism no more as a transient deficit but among long-term sequelae. The appearance of complex dysarthria in the postoperative period is a negative prognostic factor for the long-term persistence of speech disturbances.
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http://dx.doi.org/10.1007/s00381-019-04252-7DOI Listing
June 2020

Cranioplasty in children: time for a paradigm shift.

Authors:
Paolo Frassanito

Childs Nerv Syst 2019 09 1;35(9):1457-1458. Epub 2019 Jun 1.

Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.

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http://dx.doi.org/10.1007/s00381-019-04165-5DOI Listing
September 2019

Craniocerebral disproportion after decompressive craniectomy in infants: The hidden enemy of cranial repair?

Childs Nerv Syst 2019 09 27;35(9):1467-1471. Epub 2019 May 27.

Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Introduction: Cranioplasty aims at restoring the physiological integrity and volume of the skull. Any disproportion between the intracranial content and the volume of the container may favor the occurrence of complications. A classification of volume mismatches is proposed. A negative mismatch, consisting of intracranial content minor to skull volume, is well represented by the sinking flap. On the other side, a positive mismatch, consisting of intracranial content higher than skull volume, usually depends on CSF collection or hydrocephalus once the brain edema is regressed. Though, in children, this condition may result from physiological brain growth after decompressive craniectomy. Treatment algorithm based on this classification is presented.

Illustrative Case: A 1-year-old boy with a severe traumatic brain injury underwent right decompressive craniectomy, evacuation of subdural hematoma, and dural expansion at another institution. After failure of autologous bone-assisted cranioplasty for infection, a helmet was recommended in order to postpone the cranial repair. Patient was admitted to our institution 3 years later. CT scan showed brain herniation through the cranial defect, associated to a condition of acquired craniocerebral disproportion, due to the condition of "open skull". Augmented hydroxyapatite cranioplasty (CustomBone, Finceramica, Faenza, Italy) was performed in order to manage this rare condition of positive volume mismatch. Subsequent course was uneventful and no complication was recorded at 30-month follow-up.

Conclusions: This illustrative case highlights the possible occurrence of a positive structural mismatch between the skull and the intracranial content after decompressive craniectomy, thus configuring a condition of acquired craniocerebral disproportion, aside of other brain or CSF complications. We firstly recognize this condition in the literature and propose it as a possible factor affecting the outcome of cranioplasty in infants and young children.
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http://dx.doi.org/10.1007/s00381-019-04166-4DOI Listing
September 2019

The growth of the neurocranium: literature review and implications in cranial repair.

Childs Nerv Syst 2019 09 14;35(9):1459-1465. Epub 2019 May 14.

Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair.

Methods: A search of the electronic database of Pubmed was performed, using the key word "neurocranium growth", thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review.

Results And Conclusions: The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions.
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http://dx.doi.org/10.1007/s00381-019-04193-1DOI Listing
September 2019

Multimodal Management of Aggressive Recurrent Aneurysmal Bone Cyst of Spine: Case Report and Review of Literature.

World Neurosurg 2019 Jun 20;126:423-427. Epub 2019 Mar 20.

Neurochirurgia Infantile, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy.

Background: Different treatment options have been proposed for aneurysmal bone cysts (ABCs) with sclerotherapy favored as primary treatment and surgery remaining the mainstay of treatment in case of compression of neural structures. Recurrent spinal ABCs are burdened by increased risk of spinal deformity and instability, further complicating the management of these cases.

Case Description: A 15-year-old boy presented with acute symptoms and signs of spinal cord compression due to a large thoracic ABC. Subtotal resection of the lesion achieved optimal decompression of neural structures with good neurologic recovery, but the remnant of the lesion rapidly grew with recurrent spinal cord compression after 40 days. The patient underwent total surgical resection with full neurologic recovery. Unfortunately, recurrence of the lesion was documented at 3-months' follow-up. This was successfully treated with percutaneous injection of hydroxyapatite cement. Two years' follow-up ruled out any further recurrence of the lesion. Furthermore, spinal deformity and instability were also excluded.

Conclusions: Percutaneous sclerotherapy with hydroxyapatite cement proved to be highly effective and safe in the treatment of spinal ABC, though surgery remains mandatory in case of spinal cord compression. The main advantage of sclerotherapy with hydroxyapatite cement seems to be the capacity to regenerate bone with normal radiologic features.
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http://dx.doi.org/10.1016/j.wneu.2019.02.246DOI Listing
June 2019

Correction to: Central nervous system (CNS) neuroblastoma. A case-based update.

Childs Nerv Syst 2019 May;35(5):899

Pediatric Neurosurgery, Institute of Neurosurgery, Catholic University Medical School, Rome, Italy.

Unfortunately in the original publication, the affiliation provided for the author G. Tamburrini was incorrect. The correct affiliation for G. Tamburrini should read as follows.
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http://dx.doi.org/10.1007/s00381-019-04100-8DOI Listing
May 2019

Piezosurgery in Pediatric Neurosurgery.

World Neurosurg 2019 Jun 2;126:e625-e633. Epub 2019 Mar 2.

Neurochirurgia Pediatrica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia; Istituto di Neurochirurgia, Università Cattolica del Sacro Cuore, Roma, Italia.

Background: Piezosurgery (PS) has gained increasing dispersion in neurosurgery. In pediatric neurosurgery, the experience is limited to craniosynostosis surgery. The present study assesses PS in the pediatric population, also considering outcomes and complications in cranial and spinal procedures.

Methods: All consecutive craniotomies and laminotomies, performed with PS (group A) or conventional osteotomes (group B) in the 2014-2017 period were reviewed. The following variables were analyzed: dural tears, estimated blood loss and need of transfusion, cosmetic outcome (Sloan score), and operative times. A review of the pertinent literature is included.

Results: 172 children were enrolled, 90 in group A and 82 in group B. The mean follow-up time was 2.1 years. A statistically significant difference in favor of group A was found about EBL (105 vs. 113 ml) and late outcome (Sloan class A 98.5% vs. 91.5%). PS also reduced the risk of dural tears (1 vs. 7 cases in groups A and B, respectively) and blood transfusion (52% vs. 55.5%) but without statistical significance. The operative times were significantly shorter in group B (13 vs. 23 minutes), although the newer PS plus (PSP) was demonstrated to significantly shorten these times compared with the traditional PS (3.5 vs. 6.5 minutes for orbitotomy and 7.5 vs. 9.5 minutes for hemicraniotomy).

Conclusions: PS is a safe and effective tool that can be specifically recommended for bone splitting and graft, laminotomy, and craniotomy in cosmetically eloquent areas. The limit of operation times can be overcome by a learning curve in neurosurgery and PSP.
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http://dx.doi.org/10.1016/j.wneu.2019.02.103DOI Listing
June 2019

Bony Decompression for Chiari Malformation Type I: Long-Term Follow-Up.

Acta Neurochir Suppl 2019;125:119-124

Paediatric Neurosurgery, Agostino Gemelli Hospital Foundation, Institute of Neurosurgery, Catholic University of Rome, Rome, Italy.

Background: Several surgical techniques are used for the management of Chiari malformation type I (CM-I). Bony posterior fossa decompression is considered a good option in children, though with a higher risk of requiring reoperation. However, there is not enough evidence from the series in the literature, which are often limited by inadequate follow-up. The goal of this study was to assess the effectiveness of suboccipital craniectomy alone in children after long-term follow-up.

Methods: Forty-two children (25 female and 17 male; mean age 6.7 years), operated on with bony decompression alone, were retrospectively reviewed. All patients underwent suboccipital craniectomy. Thirty-eight children required C1 laminectomy, and 21 also underwent dural delamination on the basis of intraoperative ultrasound investigations. The outcome was assessed using the traditional measurement and the Chicago Chiari Outcome Scale (CCOS). The mean follow-up period was 11.3 years (range 5-15 years).

Results: Headache was the most frequent preoperative symptom (81%), followed by neck pain (40%), vertigo (40%), ataxia (26%), and upper and lower extremity paraesthesia (26%). Syringomyelia was present in 19 patients (45%). Resolution and significant improvement of preoperative clinical symptoms were observed in 36.5% and 21.5% of cases, respectively. Three children required adjunctive surgery for symptom recurrence (7%). The tonsil position and syringomyelia were normalized or improved in 50% and 79% of cases, respectively. No complications occurred. According to the CCOS scores, 69.5% of children had an excellent outcome, 28.5% had a functional outcome and 2% had an impaired outcome.

Conclusion: Bony decompression alone is an effective, safe and long-lasting treatment for children with CM-I. A certain risk of symptom recurrence requiring new surgery exists, but it is widely counterbalanced by the low risk of complications. Careful patient selection is crucial for a good outcome. Prospective and randomized studies are needed for further validation.
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http://dx.doi.org/10.1007/978-3-319-62515-7_17DOI Listing
August 2019

Rehabilitation in systemic sclerosis: proposed personalised rehabilitation programme.

G Ital Med Lav Ergon 2018 12;40(4):248-256

Physical Medicine and Rehabilitation Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; University of Pavia, Italy.

Objectives: Systemic sclerosis is a multisystem autoimmune disease that causes chronic widespread obliterative vasculopathy of the small arteries associated with various degrees of tissue fibrosis. The prognosis of the disease depends largely on the visceral involvement; however musculoskeletal involvement is an important factor to functional disability. Suffering from a chronic auto-immune disease, such as Systemic Sclerosis, compromises the quality of life and the work ability. The rehabilitative treatment may be a viable option for improving the quality of life, but there are few studies to support this hypothesis in adequate population. (Rehabilitation is still an under- studied field of research). Aim: Proposed personalised rehabilitation programme, with a multilocalized, multidisciplinary approach specifically designed for patients with Systemic Sclerosis.

Methods: Retrospective study. Setting: Rehabilitation Institute, inpatients. Population: Forty-three patients affected by systemic sclerosis. Methods: Patients underwent a rehabilitation programme of 3 weeks. Three cycles of rehabilitation in 3 consecutive years were administered. The priority outcome measure was the Health Assessment Questionnaire-Disability Index (HAQ-DI). The effectiveness of treatment cycles repeated at 1-year intervals was also compared to the first cycle.

Results: Each treatment had an acute beneficial effect, leading to an improvement in the disability score after each of the three cycles (admission vs discharge: 1.2±0.6 vs 0.8±0.6, p minor than 0.0001, 1.3±0.6 vs 1.0±0.6, p minor than 0.0001 and 1.4±0.7 vs 1.1±0.7, p minor than 0.0001). The improvement in HAQ-DI scores after repeated cycles was progressively lower, but the difference in efficacy was not statistically significant (p=0.38 and p=0.17 for the comparison between the second and the first and the third and the first cycles respectively).

Conclusions: The multilocalized, multidisciplinary protocol developed by our rehabilitation team led to a significant reduction in disability perceived by patients, independently of the disease duration. The beneficial effects at the end of the first cycle were reproduced in the subsequent cycles. Nevertheless, there was a tendency of progressive efficacy reduction in following cycles, due to increased disability caused by disease stage. Impact of rehabilitation: We believe that our results demonstrate the utility of personalised, multilocalized, multidisciplinary rehabilitation treatment in slowing the evolution of systemic sclerosis.
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December 2018

Custom-made hydroxyapatite for cranial repair in a specific pediatric age group (7-13 years old): a multicenter post-marketing surveillance study.

Childs Nerv Syst 2018 11 10;34(11):2283-2289. Epub 2018 Jul 10.

Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: CustomBone Service (CBS) is a patient-specific, biocompatible, and osteoconductive device made of porous hydroxyapatite, indicated for cranial reconstruction in adults and children. Adult literature data report a failure rate of about 8%. The aim of this Post-Marketing Surveillance study is to verify the hypothesis that CBS in children aged 7-13 years old shows a failure rate not superior to adults.

Materials And Methods: Inclusion criteria were age at implantation ranging 7-13 years old, with at least 1 year elapsed from the date of surgery. The degree of satisfaction of surgeons and patients was assessed.

Results: Data about 76 implants in 67 patients (M:F = 41:26) were obtained from 28 centers across 7 European countries. The mean age at surgery was 10.03 ± 1.72 years, with age stratification almost equally distributed. Fifty-nine subjects received one CBS, 7 subjects two and one subject received three CBS. Main etiologies were trauma (60.5%), malformation (11.8%), bone tumor (10.5%), and cerebral tumor (7.9%). Main indications to CBS were decompression (47.4%), autologous bone resorption (18.4%), tumor resection (11.8%), malformation (9.2%), comminuted fracture (5.3%), and other materials rejection (5.3%). Main implantation sites were fronto-parieto-temporal (26.3%), parietal (23.7%), frontal (11.8%), fronto-temporal (10.5%), and parieto-temporal (7.9%). CBS was chosen as first line of treatment in 63.1% of the cases. Mean follow-up was about 36 months. Eleven adverse events (14.5%) were reported in nine devices. Five CBS required explantation (three cases of infection, one fracture, and one mobilization). Failure rate was 6.58%, which is statistically not superior to the explantation rate recorded in adults (two-sided 95%, CI 2.2-14.7%). Satisfaction of surgeons and patients was of about 95%.

Conclusion: CBS is a safe and effective solution for cranial repair in pediatric patients. In particular, over the age of 7, CBS shows a rate of failure as low as in adults.
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http://dx.doi.org/10.1007/s00381-018-3905-8DOI Listing
November 2018

BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche.

Bone 2018 07 17;112:58-70. Epub 2018 Apr 17.

Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; Fondazione Policlinico Universitario "Agostino Gemelli", 00168 Rome, Italy. Electronic address:

Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS patients. Also, Bbs9 expression increased during in vivo ossification of rat sutures. BBS9 functional knockdown affected the expression of primary cilia on patient suture cells and their osteogenic potential. Computational modeling of the upregulated protein isoforms (observed in patients) predicted that their binding affinity within the BBSome may be affected, providing a possible explanation for the aberrant suture ossification in NCS.
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http://dx.doi.org/10.1016/j.bone.2018.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970090PMC
July 2018

Central nervous system (CNS) neuroblastoma. A case-based update.

Childs Nerv Syst 2018 05 8;34(5):817-823. Epub 2018 Mar 8.

Pediatric Neurosurgery, Institute of Neurosurgery, Catholic University Medical School, Rome, Italy.

Background: Primary central nervous system (CNS) neuroblastoma is a rare intracranial tumor affecting children mainly in the first years of life. It is usually a supratentorial tumor with a wide spectrum of clinical presentation, seizures, and focal neurological deficits being the most common presenting signs.

Case Description: A 2-year-old child was admitted to our ward after a generalized seizure. Neurological examination was normal. Radiological studies showed a small DWI hyperintense lesion of the right rectus gyrus. Follow-up brain MRI 8 months later showed a huge growth of the tumor (90 × 80 × 65 mm) with polycyclic and apparently defined margins, cystic components, and diffuse contrast enhancement. Complete tumor removal was performed in two planned surgical steps. Histological diagnosis was CNS neuroblastoma. At a follow-up of 8 months, the child is in good clinical and neurological condition and is completing chemotherapy treatment according to the SIOP PNET 4 protocol.

Discussion And Conclusion: A thorough review of the literature confirms that primary CNS neuroblastoma has to be considered a distinct entity. The disease related mortality is 12.5%, lower than the one usually reported for other previously described as PNETs tumors. The most relevant factors influencing prognosis are the possibility of obtaining a complete tumor removal and age more than 3 years, which allows to include radiotherapy among treatment options.
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http://dx.doi.org/10.1007/s00381-018-3764-3DOI Listing
May 2018

Effectiveness of Extracorporeal Shock Wave Therapy and kinesio taping in calcific tendinopathy of the shoulder: a randomized controlled trial.

Eur J Phys Rehabil Med 2018 Jun 29;54(3):333-340. Epub 2017 Nov 29.

Unit of Neuromotor Rehabilitation, Istituti Clinici Scientifici Maugeri IRCCS Rehabilitation Center Montescano, Pavia, Italy.

Background: Extracorporeal Shock Wave Therapy (ESWT) is effective in the treatment of calcific tendinopathy of the rotator cuff, eliciting an analgesic/anti-inflammatory action and promoting tissue regeneration. Kinesio taping (KT), another recently-introduced rehabilitative tool, exerts an analgesic and biomechanical action on joints and muscles. ESWT and KT may have a synergic effect when used in combination, but the effectiveness of the association has not been established.

Aim: The aim of this study was to test if the association of KT with ESWT is superior to ESWT alone in the treatment of rotator cuff calcific tendinopathy.

Design: Randomized controlled trial.

Setting: Rehabilitation Institute outpatients.

Population: Forty-two patients with rotator cuff calcific tendinopathy were randomly assigned to the experimental group (ESWT+KT, N.=21) or control (ESWT, N.=21).

Methods: In the experimental group, patients underwent three sessions (once a week for 3 weeks) of ESWT with KT applied at the end of each session. Controls underwent three sessions of ESWT only. All patients were assessed before treatment (T0) and at 1 (T1), 4 (T2) and 12 weeks (T3) after the end of treatment with the following outcome measures: a visual analogue scale (VAS), the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Subjective Shoulder Rating Questionnaire (SSRQ), and Oxford Shoulder Score (OSS).

Results: Both groups showed significant improvement in all outcome measures, but the time course differed between the two groups. At T1 vs. T0, the improvement was significantly better in ESWT+KT than ESWT on VAS (P=0.007), DASH (P<0.0001) and SSRQ (P=0.0001). Successive improvements at T2 vs. T1 and T3 vs. T2 did not differ significantly between the groups. At the end of follow-up, ESWT+KT still showed significantly greater improvement than ESWT on VAS (P=0.02) and SSRQ (P=0.038).

Conclusions: KT associated with ESWT seems to improve the recovery in rotator cuff calcific tendinopathy with a faster therapeutic response compared to ESWT only.

Clinical Rehabilitation Impact: Our results suggest the effectiveness of using KT as adjuvant therapy to ESWT in rotator cuff calcific tendinopathy, through enhancing the short-term analgesic action and the medium- to long-term biological-regenerative effects.
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http://dx.doi.org/10.23736/S1973-9087.17.04749-9DOI Listing
June 2018

Problems of reconstructive cranioplasty after traumatic brain injury in children.

Childs Nerv Syst 2017 Oct 6;33(10):1759-1768. Epub 2017 Sep 6.

Department of Neurosurgery, International Neuroscience Institute, Hannover, Germany.

Cranial repair after traumatic brain injury in children is still burdened by unsolved problems and controversial issues, mainly due to the high rate of resorption of autologous bone as well as the absence of valid alternative material to replace the autologous bone. Indeed, inert biomaterials are associated to satisfactory results in the short period but bear the continuous risk of complications related to the lack of osteointegration capacity. Biomimetic materials claiming osteoconductive properties that could balance their mechanical limits seem to allow good cranial bone reconstruction. However, these results should be confirmed in the long term and in larger series. Further complicating factors that may affect cranial reconstruction after head injury should be identified in the possible associated alterations of CSF dynamics and in difficulties to manage the traumatic skin lesion and the surgical wound, which also might impact on the cranioplasty outcome. All the abovementioned considerations should be taken into account when dealing with the cranial reconstruction after decompressive craniectomy in children.
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http://dx.doi.org/10.1007/s00381-017-3541-8DOI Listing
October 2017