Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

Frontal sinus ablation (Riedel-Mosher’s procedure): indications and role in the endonasal endoscopic era.

BACKGROUND: The aim of this article is to describe the Riedel-Mosher’s surgical technique and identify its current role in the endoscopic endonasal era based on the experience of a tertiary care medical centre. It also provides a brief excursus on materials available for frontal reconstruction. METHODS: A retrospective review of patients submitted to Riedel-Mosher’s procedure from 2005 to 2018 at a single tertiary care centre was carried out. Details of the surgical technique along with data on frontal reconstruction timing and materials used were collected. RESULTS: A total of 21 patients (16 males and 5 females) underwent the Riedel-Mosher’s procedure. The age of the patients ranged from 15 to 84 years. The underlying pathology was represented mainly by chronic osteitis of the frontal bone (17 cases), followed by benign tumours (3 cases) and malignancy (1 case). Perioperative complications occurred in 3 patients. Cranioplasty was carried out only on 16 cases and delayed by an average time of 10 months. Materials for reconstruction included titanium, ceramic, plastic and free flap . CONCLUSIONS: Nowadays, Riedel-Mosher’s procedure is still indicated in selected cases of benign and malignant pathologies of the frontal sinus and/or frontal bone. Surgical expertise is key to approach the frontal sinus safely. Its reconstruction requires proper planning and a wide variety of materials to perform it is now available.

Insect frass in stored cereal products as a potential source of Lactobacillus sanfranciscensis for sourdough ecosystem.

AIM: Insect frass samples were collected from Drosophila melanogaster, Plodia interpunctella, Rhyzopertha dominica, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Tribolium confusum and Tribolium castaneum to elucidate if they can be the origin of Type I sourdough micro-organisms (Lactobacillus sanfranciscensis and Candida milleri). METHODS AND RESULTS: Selective enrichments were carried out to isolate lactic acid bacteria (LBA) and yeast. A metagenetic analysis, targeted on bacterial 16S rRNA gene and fungal ITS region, was performed by using Illumina MiSeq protocol. In cultivation conditions, Lactococcus garvieae and Rhodotorula mucilaginosa were the most frequently species among LAB and yeasts respectively. The Next Generation Sequencing approach revealed that Enterobacteriaceae, Pseudomonadacae and Bacillaceae were the dominating taxa, accounting for 61% of the bacterial community. Lactobacillus genus showed a relative abundance of only 0·36%, but L. sanfranciscensis proved to be the species most frequent between lactobacilli and predominant in faecal samples of T. castaneum and T. confusum larvae. The core fungal microbiota was constituted by Saccharomycetales, Pleosporaceae and Nectriaceae that attained the 51% of recognized OTUs. While the most abundant yeast genus was Candida (17·1%), sequences belonging to C. milleri were not found. CONCLUSIONS: Frass released by the insects of stored cereal products can be the natural reservoir of L. sanfranciscensis. SIGNIFICANCE AND IMPACT OF THE STUDY: Insect dejections are potential sources of novel strains for controlled bakery productions.

Transorbital endoscopic assisted management of intraorbital lesions: lessons learned from our first 9 cases.

BACKGROUND: The management of intraorbital lesions is challenging and it is strongly dependent to their nature, position and biological behaviour. Traditionally, the superior and lateral compartments of the orbit are addressed via lateral orbitotomy or transcranial approaches. Herein we present our preliminary experience in the management of selected supero-lateral intraorbital lesion through an endoscopic-assisted superior-eyelid approach. METHODOLOGY: All cases of intraorbital lesion treated in two Italian tertiary care referral centres using a superior eyelid endoscopic-assisted transorbital approach were retrospectively reviewed. RESULTS: Nine patients have been analysed. The aim of surgery was diagnostic in 5 cases and curative in the remaining 4 patients. Significant tissue biopsy was obtained in all the five diagnostic procedures. Complete resection was obtained in 3/4 lesions. No major intra- or postoperative complications have been observed. Mean surgical time was 68 minutes. Mean hospitalization time was 4.4 days. All patients were satisfied about the surgical procedure, as emerged by the post-operative counselling. At present, the mean follow-up time is 18 months, ranging from 11 to 25 months. CONCLUSIONS: Our preliminary results are promising with successful functional and cosmetic outcomes and reduced morbidity for the patient. This approach should be considered as an option for selected intraorbital lesions.

Endoscopic endonasal management of non-functioning pituitary adenomas with cavernous sinus invasion: a 10- year experience.

BACKGROUND: The management of Non-Functioning Pituitary Adenoma (NFPA) invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy. METHODS: We undertook a retrospective review of 56 cases of NFPA with CS invasion treated through an endoscopic endonasal approach (EEA) between 2000 and 2010. The Knosp classification was adopted to describe CS involvement using information from preoperative MRI and intraoperative findings. Extent of resection and surgical outcomes were evaluated on the basis of postoperative contrast-enhanced MRI. Endocrinological improvement and visual outcomes were assessed according to the most recent consensus criteria. RESULTS: EEA was performed using direct para-septal, trans-ethmoidal-sphenoidal or trans-ethmoidal-pterygoidal-sphenoidal approach. Visual outcomes improved in 30 (81%) patients. Normalization or at least improvement of previous hypopituitarism was obtained in 55% of cases. A gross total resection was achieved in 30.3% of cases. The recurrence-free survival was 87.5%, with a mean follow-up of 61 months (range, 36-166 months). No major intraoperative or postoperative complications occurred. DISCUSSION: EEA is a minimally-invasive, safe and effective procedure for the management of NFPA invading the CS. The extent of CS involvement was the main factor limiting the degree of tumor resection. The EEA was able to resolve the mass effect, preserving or restoring visual function, and obtaining adequate long-term tumor control.

Prevalence of double pituitary adenomas in a surgical series: Clinical, histological and genetic features.

BACKGROUND: The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. AIM: We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. SUBJECTS AND METHODS: One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. RESULTS: One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. CONCLUSIONS: The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow- up.

Endonasal approaches to the sellar and parasellar regions: closure techniques using biomaterials.

PURPOSE: We reviewed the clinical outcomes resulting from various closure techniques used following endoscopic endonasal surgery for lesions in the sellar and parasellar regions. We compared our current closure technique, which uses a biological matrix of native equine collagen (TissuDura) fixed with fibrin sealant (Tisseel), with the technique we employed previously, using autologous materials, in order to assess the comparative efficacy and tolerability of both methods over the medium- to long-term. METHODS: A review was conducted of all cases of endonasal endoscopic intervention carried out in our institution between 1997 and 2007. Operations performed between January 1st 1997 and December 31st 2003 involved a sellar closure technique using autologous materials, either alone or supported by fibrin sealant. From January 1st 2004, sellar reconstruction techniques involving resorbable heterologous materials were used in the closure phases. Post-operatively, clinico-endoscopic assessments took place at 15 days, 1, 3, and 6 months and yearly thereafter, supplemented by magnetic resonance imaging (MRI) scanning at 3 months and annually. RESULTS: Between January 1st 1997 and December 31st 2003, 79 operations were performed in which the sellar closure technique involved the use of autologous materials. Between January 1st 2004 and January 1st 2008, 125 operations were performed in which biomaterials were used for sellar closure. The incidence of complications (fluid fistula) was 2.5% in the autologous materials closure group and 1.6% in the biomaterials closure group. The most marked difference between the two approaches was seen at 1-month follow-up, when restoration of mucociliary transport in the sphenoidal sinus and physiological functionality of the nasal mucosa and paranasal sinuses were observed to be superior in the biomaterials patient cohort. CONCLUSIONS: The development of biomaterials for closure of the sellar floor offers a viable alternative to traditional techniques using autologous materials.

Extended Endoscopic Endonasal Approach for Suprasellar Craniopharyngioma.

Objectives We illustrate a suprasellar craniopharyngiomas treated with an extended endoscopic endonasal approach (EEEA). Design Case report of a 43-year-old male affected by cerebral lesion located in suprasellar region involving the third ventricle and compressing the neurovascular structures, causing an anterosuperior dislocation of the chiasma. There is a complete disruption of the pituitary stalk that can explain the clinical finding of partial anterior hypopituitarism and hyperprolactinemia. The lesion is characterized by a solid and cystic component. Considering the absence of lateral extension and the suprasellar location of the lesion, an EEEA is preferred. Setting University Hospital "Ospedale di Circolo," Department of Neurosurgery, Varese, Italy. Participants Neurosurgical and ENT Skull Base Team. Main Outcome Measures A bilateral parasagittal approach is performed using a four-hand technique. The first step of the surgery is the preparation of the Hadad's flap. The approach is extended to the planum sphenoidalis to expose the suprasellar region. The lesion is completely removed employing also an ultrasound aspirator. Skull base reconstruction is performed with three-layer technique: graft of fat tissue, fascia lata, and nasoseptal flap. Results No postoperative complications occurred. In the post-op, the patient presents a panhypopituitarism and an improvement in neurological status. The visual deficit remains stable. Post-op magnetic resonance imaging at 1 year documents the complete absence of pathological contrast enhancement. Conclusions EEEA is a feasible approach in treating craniopharyngioma with suprasellar extension. The advantages include optimal visualization, good resection rate, and absence of brain retraction. The link to the video can be found at: https://youtu.be/IYm-8P1jbBo .

Cooked garlic and antioxidant activity: Correlation with organosulfur compound composition.

The antioxidant properties and the main beneficial organosulphur compounds of home-cooked garlic samples were studied in order to establish relationships between them. Antioxidant activity was tested by free radical scavenging against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis-(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS+), Fe(III) reducing ability (FRAP) and linoleic acid co-oxidation initiated by soybean lipoxygenase in a micelle system. DPPH, ABTS and FRAP assays showed the highest activity for raw garlic samples, while ß-carotene bleaching assay yielded the highest activity for stir-fried garlic. Pure organosulphur compounds tested by DPPH, FRAP and ß-carotene bleaching assays showed that allicin had an antiradical action mechanism, as well as iron reducing capacity; while antioxidant activity was the main mechanism for ajoenes and 2-VD. To our knowledge, this study is the first demonstration that home-cooked garlic retains its antioxidant activity, and, at the same time, elucidates the mechanisms involved in this activity.

Brain tumours in infants. Preferred treatment options.

Since the advent of CT scan and MRI, the diagnosis of neonatal infantile brain tumours and related diseases is more easily accomplished; their rarity is reflected in the small number of cases reported. Astrocytomas and teratomas are the most common oncotypes in infants and particularly in neonates. Surgical mortality rates are not high and have decreased because of the advances of diagnosis and improvements in treatment. However, the survival rates are disappointing. Follow-up shows little improvement in last 2 decades. Adjuvant therapy is still a problem; radiotherapy gives a small percentage of favourable later neuropsychological results. Postoperative chemotherapy added to maximal surgical resection and delayed irradiation may prolong survival with only minimal short term neurotoxicity in very young children with malignant tumours. Different protocols of chemotherapy are suggested but still not definitely accepted. Radical surgery seems to have a higher chance of success in neonates than infants and remains the less aggressive means; in low grade gliomas after total removal it may be preferable to perform a second operation if the tumour recurs and withhold irradiation and chemotherapy until after 3 years of age.

Evolution of childhood central diabetes insipidus into panhypopituitarism with a large hypothalamic mass: is 'lymphocytic infundibuloneurohypophysitis' in children a different entity?

We report on a 15-year-old girl who had presented with acute onset central diabetes insipidus at the age of 8 years; this was followed by growth failure due to acquired growth hormone deficiency. Initial magnetic resonance imaging showed a uniformly enlarged pituitary stalk and absence of posterior pituitary hyperintensity. Frequent patient examination and magnetic resonance imaging gave unchanged results until after 5 years a large hypothalamic mass and panhypopituitarism were found. Dynamic magnetic resonance imaging documented hypothalamic-pituitary vasculopathy. Histopathological examination revealed perivascular inflammatory lymphoplasmic infiltrates with no granulomatosis or necrosis and negative staining for S-100 protein, suggesting autoimmune inflammatory disease (lymphocytic infundibuloneurohypophysitis?). The response to glucocorticoid pulses (30 mg/kg per day for 3 days i.v.) was favorable. the hypothalamic mass being halved and partial anterior pituitary function recovery maintained for 2 years after the start of treatment. We suggest that long-term surveillance is needed for isolated and chronic thickening of the pituitary stalk and that dynamic magnetic resonance imaging can contribute to the demonstration of hypothalamic-pituitary vascular impairment associated with local vasculitis.

Dependence of fibroblast autofluorescence properties on normal and transformed conditions. Role of the metabolic activity.

The dependence of autofluorescence properties on the metabolic and functional engagement and on the transformation condition was studied on single cells. Normal Galliera rat fibroblasts at low subculture passage (cell strain), at high subculture passage (stabilized cell line), and transformed cell line derived from a rat sarcoma were used as a cell model. The study was performed by microspectrofluorometric and fluorescence imaging technique. The autofluorescence properties of cells were studied by excitation at two wavelengths, namely 366 nm and 436 nm, that are known to favor the emission of different fluorophores. Spectral shape analysis indicated that under excitation at 366 nm autofluorescence is ascribable mainly to coenzyme molecules, particularly to reduced pyridine nucleotides, while under excitation at 436 nm, flavin and lipopigment emission is favored. The energetic metabolic engagement of the different cell lines was analyzed in terms both of parameters related to anaerobic-aerobic pathways (biochemical assay) and of mitochondrial features (supravital cytometry). The results showed that the cell strain and the stabilized and transformed cell lines can be distinguished from one another on the basis of both overall fluorescence intensity and the relative contributions of spectral components. These findings indicated a relationship between autofluorescence properties and energetic metabolism engagement of the cells that, in turn, is dependent on the proliferative activity and the transformed condition of the cells. In that it is a direct expression of the energetic metabolic engagement, autofluorescence can be assumed as an intrinsic parameter of the cell biological condition, suitable for diagnostic purposes.

Enzyme-assisted cell photosensitization: a proposal for an efficient approach to tumor therapy and diagnosis. The rose bengal fluorogenic substrate.

Rose bengal, a xanthene derivative among the most efficient producer of singlet oxygen, was submitted to a chemical modification consisting in the introduction of an acetate group into the aromatic ring fluorophore structure. The acetate group acts as a quencher, thus inactivating both fluorescence and photosensitization properties of the molecule. In the modified structure, rose bengal acts as a fluorogenic substrate giving rise to the cellular reaction termed fluorochromasia. The acetate group is recognized by a carboxylic esterase activity that splits it. Removal of the quencher group results in restoring the native structure of photosensitizer inside the cells. The intracellular turnover of rose bengal acetate was studied in rat glioma-derived cultures cells, in terms of the balance of the processes of influx and enzyme hydrolysis of the fluorogenic substrate, and of the efflux of the fluorescent product. A large intracellular accumulation of photosensitizer is obtained when treatments are performed with the fluorogenic substrate, even at the drug concentration at which rose bengal does not enter the cells. The intracellular localization allows rose bengal to exert a more effective photosensitization effect. Provided that the quencher group is selected according to the metabolic properties of the tumor cells, the use of fluorogenic substrates as photosensitizer precursors could improve fluorescence diagnosis and the photodynamic therapy of tumors, exploiting the biological properties that distinguish pathological from normal conditions.

Surgical treatment of craniosynostosis.

The authors report their experience with the cranial recontouring techniques in the treatment of craniosynostoses. The results obtained treating sixteen children suggest that these techniques can be tolerated well by patients, with very limited postoperative complications. It is underlined that the precocity of the surgical treatment is an indispensable prerequisite in order to obtain satisfactory clinical and cosmetic results.

Spontaneous intracerebral hemorrhage: medical or surgical treatment.

Eighty-six cases of spontaneous intracerebral haemorrhage, some treated by surgery, some by medical therapy, were studied retrospectively. The two groups, characterized on the basis of numerous parameters were compared: the findings are discussed and interpreted in the hopes of indicating a correct therapeutic strategy.

Chemotherapy plus immunotherapy for patients with primary and metastatic brain tumors.

The authors report two clinical trials concerning chemotherapy and immunotherapy combined in the treatment of primary and metastatic brain tumors. In the first study bacillus Calmette-Guerin (BCG) and in the second Levamisole (LMS) were utilized as immunostimulating agents. Chemotherapy was performed with BCNU or CCNU in association with surgery and/or radiotherapy. The immunological response was obtained but immunotherapy failed to demonstrate any significant effect on survival.

Application of fluorescence resonance energy transfer techniques to the study of lectin-binding site distribution on Paramecium primaurelia (Protista, Ciliophora) cell surface.

Fluorescence resonance energy transfer (FRET) is a photophysical phenomenon occurring between the molecules of two fluorochromes with suitable spectral characteristics (donor-acceptor dye pair), and consisting in an excitation energy migration through a non-radiative process. Since the efficiency of the process is strictly dependent on the distance and reciprocal orientation of the donor and acceptor molecules, FRET-based techniques can be successfully applied to the study of biomolecules and cell component organisation and distribution. These techniques have been employed in studying Paramecium primaurelia surface membrane for the reciprocal distribution of N-acetylneuraminic acid (NeuAc) and N-acetylglucosamine (GlcNAc) glycosidic residues, which were found to be involved in mating cell pairing. NeuAc and GlcNAc were detected by their specific binding lectins, Limulus polyphemus agglutinin (LPA) and wheat germ agglutinin (WGA), respectively. Microspectrofluorometric analysis afforded the choice of fluorescein isothiocyanate and Texas red conjugated with LPA and WGA, respectively, as a suitable donor-acceptor couple efficiently activating FRET processes. Studies performed both in solution and in cells allowed to define the experimental conditions favourable for a FRET analysis. The comparative study carried out both on the conjugating-region and the non conjugating region of the surface membrane, indicates that FRET distribution appears quite homogeneous in mating-competent mating type (mt) I, whereas, in mating-competent mt II cells, FRET distribution seems to be preferentially localised on the conjugating-region functionally involved in mating cell pairing. This difference in the distribution of lectin-binding sites is suggested to be related to mating-competence acquisition.

[Neuropsychic development in children born with spina bifida]. / Lo sviluppo neuropsichico dei bambini nati con spina bifida.

The authors present the outcome of 42 patients operated at birth for closure of the spinal malformation. The age of patients at first observation ranged from 3 months to 21 years (mean 8.3 years); 7 patients (16.7%) had a close spina bifida, 35 (83.3%) had an open spina bifida and 30 (85.7%) of them developed hydrocephalus. The protocol included neurological evaluation, determination of development quotient using the Griffith's scale and intelligence quotient using the Wise-R scale. Adolescents underwent also the Blacky pictures test and Offer's interview. Verticalization and tutorial deambulation were achieved in 95.2% of patients; 76% of patients had a I.Q. > 90. The emotional situation was unsatisfactory in the majority of patients due to reduced autonomy and limited self-consideration.