Neoplasms

Nervous System Diseases

All Conditions

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

The sitting position Device sCtO2 Device BIS

The prone position Device sCtO2 Device BIS

The non invasive cerebral oxymetry (INVOS-Covidien) has been used to measure cerebral oxygen saturation.

SctO2

Ozlem Korkmaz Dilmen

Yusuf Tunali

The sitting or prone positions are used for posterior fossa surgery. Although the sitting position may cause hemodynamic instability, venous air embolism, it also provides optimum access to midline lesions, decreases intracranial pressure. The sitting position has not been only used in neurosurgery, it has been also used in the shoulder surgery. The sitting position related hypotension may reduce the cerebral perfusion pressure, therefore may cause cerebral ischemia. The sitting position related cerebral ischemia has been shown in the shoulder surgery. The non invasive cerebral oxymetry (INVOS-Covidien) has been used to measure cerebral oxygen saturation. Some studies has been done to investigate whether the sitting position cause cerebral desaturation or not in the shoulder surgery by non invasive cerebral oxymetry. The study results are controversial.

It has been investigated that the effect of the prone position on the cerebral oxygenation in the spine surgery and the investigators found that the prone position may increase cerebral oxygenation.

However, all studies have been done in patients without intracranial pathology. We speculate that due to the sitting position reduces the intracranial pressure, it may improve the cerebral oxygenation in the patients have intracranial pathology. Therefore we will compare the sitting and the prone positions effects on the cerebral oxygenation in patients undergoing posterior fossa tumour surgery by non invasive cerebral oxymetry.

Method: 62 patients have posterior fossa tumour will include the study. Patients will divide to 2 groups according to the surgical position, the prone (n=31) or the sitting (n=31). Patients heart rate, mean blood pressure (MAP), cerebral oxygen saturation (SctO2), peripheral oxygen saturation (SpO2), BIS values will record before the induction of anesthesia. Five minutes after the standard anesthesia induction all values will record and it will accept as a baseline. After that all these parameters will record in each 3 minutes until the beginning of surgery. Mean while, more than 5 % reduction in SctO2 and more than 20 % reduction in SctO2 and/or MAP will record. As well as, if the SctO2 reduces than 55 and 60 %, it will record.

The sitting or prone positions are used for posterior fossa surgery. Although the sitting position may cause significant complications such as including hemodynamic instability, venous air embolism, paradoxical air embolism (PAE), pneumocephalus, peripheral neuropathy, quadriplegia and macroglossia, it also provides optimum access to midline lesions in posterior fossa and cervical spine, improves blood and cerebral spinal fluid drainage, decreases intracranial pressure, lowers airway pressure, and improves access to the endotracheal tube and ability to observe the face for signs of cranial nerves stimulations. The sitting position has not been only used in neurosurgery, it has been also used in the shoulder surgery. The sitting position related hypotension may reduce the cerebral perfusion pressure, therefore may cause cerebral ischemia. The sitting position related cerebral ischemia has been shown in the shoulder surgery.

The non invasive cerebral oxymetry (INVOS-Covidien) has been used to measure cerebral oxygen saturation. Some studies has been done to investigate whether the sitting position cause cerebral desaturation or not in the shoulder surgery by non invasive cerebral oxymetry. The study results are controversial.

It has been investigated that the effect of the prone position on the cerebral oxygenation in the spine surgery and the investigators found that the prone position may increase cerebral oxygenation.

However, all studies have been done in patients without intracranial pathology. We speculate that due to the sitting position reduces the intracranial pressure, it may improve the cerebral oxygenation in the patients have intracranial pathology. Therefore we will compare the sitting and the prone positions effects on the cerebral oxygenation in patients undergoing posterior fossa tumour surgery by non invasive cerebral oxymetry.

Method: 62 patients have posterior fossa tumour will include the study. Patients will divide to 2 groups according to the surgical position, the prone (n=31) or the sitting (n=31). Patients heart rate, mean blood pressure (MAP), cerebral oxygen saturation (SctO2), peripheral oxygen saturation (SpO2), BIS values will record before the induction of anesthesia. Five minutes after the standard anesthesia induction all values will record and it will accept as a baseline. After that all these parameters will record in each 3 minutes until the beginning of surgery. Mean while, more than 5 % reduction in SctO2 and more than 20 % reduction in SctO2 and/or MAP will record. As well as, if the SctO2 reduces than 55 and 60 %, it will record.

Effects of the Prone and the Sitting Positions on the Brain Oxygenation in Posterior Fossa Surgery

After anesthesia induction cerebral oxygen saturation will record in each 3 minutes until the beginning of surgery

Istanbul University

MD, DESA, Associate Prof in Anesthesiology

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Hyperventilation

Respiration Disorders

Respiratory Tract Diseases

Signs and Symptoms, Respiratory

Oculocerebral Syndrome With Hypopigmentation

• Group 1: hyperventilation (ETco2 25-30 mm Hg) for 20 minutes that will start immediately after skin incision followed by normoventilation (ETco2 31-35 mm Hg) for another 20 minutes.

• Group 2: normoventilation (ETco2 31-35 mm Hg) for 20 minutes immediately after skin incision followed by hyperventilation (ETco2 25-30 mm Hg) for another 20 minutes.

evaluation of the changes of cerebral oxygen saturation during hyperventilation and normo-ventilation (using near-infrared spectroscopy) in pediatrics undergoing posterior fossa tumor resection.

cerebral oximetry

The aim of this study is to evaluate the changes of cerebral oxygen saturation during hyperventilation and normo-ventilation (using near-infrared spectroscopy) in pediatrics undergoing posterior fossa tumor resection.

Introduction:

Hyperventilation has been used for intraoperative brain relaxation for decades, Interestingly, this common practice is not based on robust evidence .

The mechanism of brain relaxation secondary to hyperventilation is attributed to the hypocapnia induced cerebral vasoconstriction and the subsequent reduction of cerebral blood volume (CBV) and intracranial volume. The CBV reduction is accompanied by the reduction in cerebral blood flow that could render the brain at ischemic risk, if the cerebral metabolic activity remains the same before and after hyperventilation. So, it is possible that inadvertent cerebral ischemia may outweigh the benefits of hyperventilation and should be subjected for further investigation.

Cerebral near-infrared spectroscopy (NIRS) is a useful non-invasive tool for regional cerebral oxygen saturation (rScO2) monitoring, which provides continuous, real time information on the balance between cerebral oxygen delivery and consumption.

Cerebral oximetry monitoring had the ability to detect clinically silent episodes of cerebral ischemia in a variety of clinical settings which could be an important safeguard for cerebral function.

Hyperventilation had been shown to significantly reduce cerebral oxygenation using near-infrared spectroscopy in patients undergoing elective abdominal surgery.

Multiple studies have shown that prolonged hyperventilation correlated with poor outcome especially in brain injured patients. 5,6 However, there is still a lack of evidence on the relationship between hyperventilation and neurological outcome in patients having craniotomy.

However, to the best of the investigator's knowledge no previous randomized controlled trials had studied the effect of hyperventilation versus normo-ventilation on cerebral oximetry in pediatrics undergoing posterior fossa tumor surgeries.

V. Study procedure:

This is a prospective, randomized controlled trial with a two-period crossover design so that the patient can act as a control to himself. Enrolled patients are children (1-6 years old) undergoing posterior fossa tumor resection. Prior to anesthetic induction, the two sensors (SAFB-SM, Covidien, Dublin, Ireland) for near-infrared spectroscopy (INVOS 5100C, Covidien, Dublin, Ireland) will be applied on the left and right sides of the forehead with the caudal border approximately 1 cm above the eyebrows to measure regional oxygen saturation (rSO2). A bispectral index (BIS) sensor will also be fixed on the left forehead (Model QUATRO, Covidien, Dublin, Ireland) to monitor the depth of anesthesia. Both sensors will be fixed to their positions using adhesive pads to avoid removal during positioning and soaking with betadine solution. Baseline values for cerebral oxygen saturation will be obtained using NIRS monitor, Standard monitors (electrocardiogram, non-invasive blood pressure, pulse oximeter) will be applied to all patients. The anesthetic management will be standardized for all patients as follows:

General anesthesia will be induced by inhalational agent 'sevoflurane' until intravenous line is secured then Fentanyl (1-2 µg/kg), Propofol (1-2 mg/Kg) will be given intravenously. Intubation will be facilitated by Atracurium (0.5 mg/kg) and confirmed by capnography. Nasopharyngeal temperature probe will be inserted for monitoring of core body temperature which will be kept between 36.5-37 C using warming blankets. A 22 G arterial cannula will be placed in the left radial artery and baseline ABG will be obtained to correlate value of Etco2 and Paco2. Anesthesia will be maintained with isoflurane in oxygen 40% and will be adjusted to maintain BIS between 40 and 60 and Atracurium infusion (0.5 mg/kg/hr). Central venous line will be inserted in the right internal jugular vein under complete aseptic condition under ultrasound guidance, wide bore peripheral cannula will be inserted for fluid management and a Foley's catheter will be inserted in the urinary bladder for urine output monitoring. Patients will be positioned in the prone position with the arms positioned and secured at the patient's side and after careful padding of the pressure points; the patient head will be supported on the forehead using a horseshoe adapter. Slight neck flection will be permitted till the anesthetist can pass two fingers easily between the chin and the chest to allow for optimum surgical exposure. Patients will be randomly assigned using concealed envelopes, according to a computer-generated random number to one of the following two treatment sequences:

* Group 1: hyperventilation (ETco2 25-30 mm Hg) for 20 minutes that will start immediately after skin incision followed by normoventilation (ETco2 31-35 mm Hg) for another 20 minutes.
* Group 2: normoventilation (ETco2 31-35 mm Hg) for 20 minutes immediately after skin incision followed by hyperventilation (ETco2 25-30 mm Hg) for another 20 minutes. The ventilation strategies will be achieved using volume-controlled mode with a tidal volume of 8 ml/kg, I/E ratio:1/2 and ETco2 will be maintained at the desired range by adjusting the respiratory rate. Positive end-expiratory pressure (PEEP) will not be applied. After removal of the bone flap and exposure of the dura matter, a 20-gauge plastic cannula will be inserted into the subdural space along the surface of the brain. This will be connected to a calibrated pressure transducer via a length of polyethylene high pressure tubing filled with normal saline. The transducer will be zeroed at ear level. During the study period, the mean subdural pressure will be recorded at 2 minutes intervals at the end expiratory phase.

Assessment phase 1: An arterial blood sample will be obtained immediately after skin incision for blood gas analysis to determine the difference between arterial and end-tidal carbon dioxide tension (Pa-ETCO2). Ventilation and ETCO2 will be kept constant for at least 20 min, which is long enough for stabilization of any vascular responses to the change in Paco2. At the end of the equilibration period (20 minutes), another arterial blood sample will be obtained to confirm that the targeted Paco2 (was achieved. The neurosurgeon, unaware of the anesthetic and ventilatory management provided, will be then asked to score the brain bulk according to a four-point scale as follows:

1. Excellent with no swelling
2. Minimal swelling, acceptable
3. Swollen but no treatment required
4. Swollen, needing treatment. After this assessment, ventilation will be changed immediately according to group assignment.

Assessment phase 2: Another 20 min of equilibration will be allowed and measurements will be repeated as previously described. During the whole period of study (40 minutes), the cerebral oximetry will be recorded at 5 minutes intervals. During this period factors that may affect cerebral oximeter will be controlled by maintaining position of the patient head, (normothermia with temperature at 36.5-37 C), within 20% of the base line blood pressure using increments of ringer solution and ephedrine boluses as appropriate, maintain PH 7.35-7.45, Hb level around 10 gm/dl guided by blood loss and repeated measurements of Hb in ABG and blood glucose level between 80-180 mg/dl. The study will be ended at this point, the subdural cannula will be removed, and surgery will proceed as normal. Specific or routine interventions for brain swelling such as a change in body position or diuretic therapy with mannitol or furosemide will not be administered until the study had ended. However, for ethical reasons, interventions will be made if requested by the surgeon and the patient will be then withdrawn from the study. Data will be collected by an independent blinded anesthesiologist using a data collection form.

• Measurement tools:

* Demographic and categorical characteristics including patient's age in years, weight in Kg, gender, type of the procedure( 4th ventricular, medulloblastoma,... )
* Both NIRS values at baseline and every 5 minutes during each phase of the study
* Subdural intracranial pressure (ICP) every 2 minutes during each phase of the study
* End tidal co2 every 5 minutes during each phase of the study
* Paco2 baseline and at the end of each phase of ventilation (20 minutes following start of phase 1 assessment and 20 minutes after start of phase 2 assessment)
* Heart rate and mean arterial blood pressure every 10 minutes.
* Brain relaxation score

The Effect of Different Ventilation Strategies on Cerebral Oxygenation Using Near Infrared Spectroscopy (NIRS) in Pediatrics Undergoing Posterior Fossa Tumor Surgery

The Effect of Different Ventilation Strategies on Cerebral Oxygenation Using Near Infrared Spectroscopy (NIRS) in Pediatrics Undergoing Posterior Fossa Tumor Surgery: Randomized Controlled Cross Over Study

NIRS value at the end of phase 1 assessment in each group

Brain relaxation score: four-point scale as follows:

1. Excellent with no swelling
2. Minimal swelling, acceptable
3. Swollen but no treatment required
4. Swollen, needing treatment. the higher the score the higher the intracranial pressure

Kasr El Aini Hospital

lecturer of anesthesia

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Wounds and Injuries

Behaviors and Mental Disorders

Hemorrhage

Subarachnoid Hemorrhage

Congenital Abnormalities

Epilepsy

Epilepsy, Temporal Lobe

Intracranial Hemorrhages

Brain Injuries

Brain Injuries, Traumatic

Hematoma

Unconsciousness

Coma

Arnold-Chiari Malformation

Supratentorial Neoplasms

Craniocerebral Trauma

Trauma, Nervous System

Cerebrovascular Disorders

Vascular Diseases

Spinal Dysraphism

Neural Tube Defects

Nervous System Malformations

Epilepsies, Partial

Syndrome

Epileptic Syndromes

Consciousness Disorders

Neurobehavioral Manifestations

Neurologic Manifestations

Chiari Malformation Type 2

Merve Tugba Ozfidan Donmez, MD

Ozlem Korkmaz Dilmen, MD

Yusuf Tunali, MD

Fatma Eren Akcil, MD

1. The primary aim of this study is to investigate the correlation between the length of ICU stay and a newly developed FIVE score in neuro-intensive care patients.
2. The secondary objectives are to evaluate the impact of the FIVE score on hospital length of stay, Modified Rankin Scale, and mortality, as well as to determine the correlation between the GCS, FOUR, and FIVE scores

Consciousness monitoring is crucial in neuro-intensive care. Despite the use of different scoring systems to establish a common language among evaluators, the Glasgow Coma Scale (GCS) remains the most widely used in clinical practice. In GCS evaluation, verbal response, motor response, and eye response are assessed. Another scoring system, FOUR (Full Outline of UnResponsiveness ) Score is similar to the Glasgow Coma Score (GCS). But it is designed to provide a more comprehensive neurological assessment. The FOUR score evaluates four areas: including eye opening, motor response, brainstem reflexes, and respiration, and assigns a score for each area. A comprehensive education regarding those scores was given the intensive care healthcare providers before the trial.

In this study, the investigators developed the Full Intracranial Validity Evaluation (FIVE) Score, by adding the mean arterial pressure and gag reflex components to the FOUR score. The investigators believe that this new score, which can be used for clinical monitoring, may offer an alternative to FOUR and GCS monitoring. According to this scoring system, in addition to the criteria for the FOUR score, patients with a mean arterial pressure between 60-130mmHg receive 2 points; patients under inotropic support with a mean arterial pressure between 60-130mmHg receive 1 point; patients with a mean arterial pressure below 60mmHg or above 130mmHg receive 0 points. Additionally, for patients with infratentorial mass, the investigators add the assessment of gag reflex in the calculation of the FIVE score. If the reflex is absent, 0 points are given; if it is unilateral, 1 point is given, and if it is preserved, 2 points are given.

The demographic data, diagnoses, systemic comorbidities, the American Society of Anaesthesiologists (ASA) score, the Charlson Comorbidity Index (CCI), and the APACHE II scores of patients were recorded.

The GCS, FOUR, and FIVE scores of the patients were recorded at neuro ICU admission, every 12 hours during neuro ICU follow-up period and discharge. In our clinic, GCS monitoring is routinely performed hourly for every patient admitted to the ICU. For patients with a decrease of two or more points in GCS score, FOUR and FIVE scores were re-evaluated and recorded without waiting for the 12 hours. Besides this, the worst, the best and the mean GCS, FOUR, and FIVE scores were recorded in the neuro ICU follow-up period. The assessment count of the GCS, FOUR, and FIVE scores during clinical follow-up was recorded.

The length of ICU and hospital stay were recorded. The Modified Rankin Scale of the patients was recorded six months after ICU discharge.

The primary aim of this study is to investigate the correlation between the length of ICU stay and a newly developed FIVE score in neuro-intensive care patients. The secondary objectives are to evaluate the impact of the FIVE score on length of hospital stay, Modified Rankin Scale, and mortality, as well as to determine the correlation between the GCS, FOUR, and FIVE scores.

A New Approach in Intensive Care Unit Consciousness Assessment: FIVE Score

The New Developed FIVE Score and Its Comparison With GCS and FOUR Scores Regarding Length of Hospital Stay Morbidity and Mortality in Neuro-intensive Care Patients. an Observational Prospective Study

Glasgow Coma Scale (GCS) and Four/Five Scores, along with the highest, lowest, and average scores, discharge scores, Modified Rankin Scores at 6 months post-discharge, and length of stay information measured upon admission to the intensive care unit will be shared.

Full Intracranial Validity Evaluation, minimum value:0, maximum value: 20, higher scores mean a better situation

Glasgow Coma Score, minimum value:3, maximum value: 15, higher scores mean a better situation

In scoring post-discharge morbidity six months after intensive care unit discharge, Modified Rankin Score is used. minimum value:0, maximum value:6, higher scores mean a worse outcome

Istanbul University - Cerrahpasa (IUC)

medical doctor

Mutism

Speech Disorders

Language Disorders

Communication Disorders

Neurodevelopmental Disorders

Mental Disorders

Psychotic Disorders

Children (0-18 years) with a tumour in the posterior fossa (cerebellum/4th ventricle/brainstem ) requiring surgery or open biopsy at one of the participating centres.

Aske F Laustsen, MD, PhD stud

Astrid M Sehested, MD

Andreas Peyrl

Jurgen Lemiere

Vladimir Benes

Steen Rosthøj, MD

Niels Clausen, MD

Karen O Møller, Nurse

Marianne Juhler, MD, Dr. med

Astrid Sehested, MD

Jonathan K Groenbaek, MD, PhD

Peder S Wehner, MD

Tuula Lönnqvist

Atte Karppinen

Jouni Pesola

Satu Lehtinen

Kristiina Nordfors

Päivi Lähteenmäki

Marika Gronroos

Ulf Nestler

Péter Hauser, MD, PhD

Andrea Carai, MD

Rosita Kiudeline

Giedre Rutkauskiene

Leonie v d Abbeele

Kirsten van Barsen

Ingrid K Torsvik

Einar Stensvold

Tore Stokland

Harald Thomassen

Johan Cappelen

Magnus Sabel

Irene Devenney

Charlotte Castor

Pernilla Grillner

Mattias Mattsson

Christoffer Ehrstedt

Pelle Nilsson

Conor Mallucci

Kjeld Schmiegelow, MD, Dr. med

Karsten Nysom, MD

The purpose of this study is to determine why up to 25% of the pediatric patients who have surgery for a tumor in the posterior fossa develops the Cerebellar Mutism Syndrome (CMS). Furthermore the purpose is to explore the clinical course and the best treatment of the syndrome.

Background:

Cancer accounts for 22 % of all deaths among children in Europe and is thus the leading non-traumatic pediatric cause of death. Central nervous system (CNS) tumours constitute 25% of all childhood cancers, and the majority of these are located in the posterior fossa. One of the most troublesome late effects after neurosurgery for such a tumour is the cerebellar mutism syndrome which is seen in up to 25% of the patients. It is characterized by mutism, hypotonia, ataxia and irritability. The exact aetiology, risk factors, clinical course and treatment have yet to be identified. The aim of this study is to accomplish that.

Method:

This is an observational prospective multicentre study that will include a minimum of 500 paediatric patients with posterior fossa CNS tumours from the Nordic countries. Additional countries might be added later once the study is running. The study has started in fall 2014 in 20 centres from 5 Nordic countries. Prior to this a pilot study was performed on 43 Danish adult patients to validate and fine-tune registration procedure. All patients will be treated according to local standards, but clinical data will be collected and imaging will be reviewed centrally.

To calculate the participation rate the annual number of included patients from each country will be compared to the number of registered patients in the cancer registers of the respective country and year.

A blood sample for genetic analysis will be collected from all patients. The patients' neurology and speech functions will be examined both pre-operatively and repeatedly post-operatively, including recording of standardised speech samples. All data will be collected trough a, for the purpose developed, online database.

Registration of data

The following data will be registered at the following 5 time points:

1. Preoperatively Hospital and country, and patient related variables (date of birth, handedness, bilingualism, sex and date of diagnosis). Medical history (Previous neurological/neuropsychological/ psychiatric problems, comorbidities, previous operations or other treatment for the tumour, previous regular use of any kind of medication). Preoperative neurological status will be examined and a language and speech test will be performed and recorded. If the patient is younger than 2 years a bedside assessment of the speech will be performed instead of a test. A blood sample for genetic analysis will be drawn together with the standard blood samples. Alternatively this can be done at any time during follow-up.
2. Postoperatively within 72 hours of surgery Operation related variables (date, duration and course of operation, surgical position, surgical approach, and tumour removal method), complications, technology employed, preoperative hydrocephalus and estimated completeness of tumour resection.
3. Postoperatively within 1-4 weeks from surgery Approximately 1-2 weeks post-op: Postoperative language and speech status and for those older than 2 years, a recording of a speech sample. Neurological examination. Glucocorticoid administration pre-, intra- or postoperatively plus other medications used to treat the CMS postoperatively and their effects. Kind(s) of imaging performed on the tumour pre- and postoperatively. Approximately 4 weeks post-op: Development and treatment of postoperative intracranial haematoma and hydrocephalus, leakage of cerebrospinal fluid and need for ventilator.
4. Postoperatively at about 2 months from surgery Postoperative development of CMS, detailed survey of the status of CMS in those affected including recording of speech sample and neurological examination. Medications used to treat the CMS since last registration and their effects.
5. Postoperatively at about 12 months from surgery Language and neurological status including a speech sample for those older than 2 years. Medications used to treat the CMS since last registration and their effects. Other anti-cancer treatment given (chemotherapy and/or radiotherapy). Results from the pathology department regarding the kind of tumour histology and genetics. Registration of whether neuropsychological assessment(s) have been performed. Kind(s) of imaging performed on the tumour since 1st follow-up. Copies of the MRIs and descriptions performed pre-op, right after the operation and approximately. 12 months post-op are obtained.

All registered data will be examined by a third party who will check for missing data or misentries in order to ensure a high quality of the data. In case of missing data or misentries the third party will contact the person who made the registration.

The database is administered by the children's cancer epidemiology group (CCEG) at Karolinska Hospital in Stockholm, which is also responsible for the Swedish children's brain tumour registry and the leukaemia database for the Nordic Society of Pediatric Hematology and Oncology (NOPHO)

Other courses:

In case of acute surgery, coma etc. information about the study and the offer to participate can be given within 7 days from the operation. In these cases preoperative data about the patient can be obtained from the patient's medical record and/or from the parents, but a preoperative speech sample cannot be performed. These patients will not be included in the analysis of whether and how preoperative speech and language status affects the risk of developing CMS, but will be included in all the other study analyses. Speech samples will be performed postoperatively in exactly the same manner as in patients that were included before operation to able to monitor the patient's speech postoperatively and register signs of the CMS.

Should the patient have posterior fossa tumour surgery performed again during the 12 months follow-up period, the patient will re-start the follow-up programme from that date. A separate pre-op and all the post-op registrations will be performed again, and used in the analysis of risk of first versus second or further surgery. New genetic blood samples will not be necessary in these cases. Should the patient have posterior fossa tumour surgery performed after the last 12 months follow-up, the patient will be offered to participate in the study again and a new consent will have to be obtained. New genetic blood samples will not be necessary in these cases.

If the patient leaves the study for any reason before the follow-up 12 months post-op, a separate form will be filled out explaining why the patient left.

If the patient turns 18 while included in the study, a new consent to participate will have to be given by the patient him- /herself.

Blood samples and analyses:

As soon as a patient has been registered, the study centre will request a 2 ml anticoagulated blood sample for genetic profiling (Single-Nucleotide Polymorphism (SNP) analysis).

The investigators will use a newly developed single nucleotide polymorphism (SNP) sequencing strategy that allows cost-effective mapping of 25-30.000 genetic polymorphisms within biological domains that could potentially be linked to the development of CMS (e.g. inflammation, vascularization, blood-brain-barrier markers, and apolipoprotein E and other lipoprotein pathway genes). The genetic data will be linked to the clinical data to identify genetic variants associated with the risk of CMS or the course of CMS. Specifically the investigators will map all SNPs in all genes that are known or are likely to be linked to these pathways, including mRNA binding sites and first order protein-protein interactions. Rather than expecting large effects of single SNPs, the strategy of this approach is to use front-line bioinformatics and pathway analyses to explore the additive effect of numerous SNPs involved in the same biological pathway. This will identify high-impact pathways, although with individual low-impact SNPs. The results obtained could guide future therapeutic approaches to CMS.

If the custodial parents do not consent to their child contributing a blood sample to the study, the child may still participate in the study, albeit not in the part involving genetic analysis. The samples as well as the rest of the study data will be protected under the Act on Processing of Personal Data and the Act on the Health Act.

All MRIs are analyzed by neuroradiologists with respect to tumour resection and neuroradiographic signs associated with CMS.

All speech recording are analyzed by speech therapists with respect to signs associated with CMS. The results of neuropsychological tests that may have been performed routinely will be separately obtained and analyzed.

Power calculations:

For the surgical hypothesis, assuming that 35% of patients are operated with an approach that has a lower risk of CMS (assumed to be 10%) and the remaining 65% of patients are operated using other approaches that carries a 20% risk of CMS, the investigators will with 80% power be able to identify a difference at a 5% significance level if the investigators include a total of 450 patients.

For the genetic analysis, several pathways and SNP-profiles will be explored with appropriate adjustments for multiple comparisons. Multiple SNPs will due to randomness be found to be related with the risk of CMS. Their true biological significance will subsequently be validated through internal validation, as the investigators will explore if other SNPs in the same biological pathway, e.g. SNPs in the same genes but not the same haplotype or SNPs that affect coding or regulatory regions in the identified risk-related genes are more significantly associated with risk of CMS than randomly selected SNPs. Furthermore, the genes/SNPs will be explored by bioinformatic predictions of the impact of the SNPs on protein-folding, binding affinity etc. Once such high-risk SNPs/genes/pathways have been identified and published, the investigators will attempt to have them confirmed in independent patient cohorts from Europe or the US. Based on a projected overall risk of CMS of 20%, a frequency of a specific SNP (or SNP-profile) of 30%, and a projected doubled risk of CMS in the group that harbour the SNP (or SNP-profile), the investigators will with 90% power be able to identify such a genetic predisposition at a 5% significance level, if a total of 343 patients are included in the study. Thus, the study has sufficient power.

To analyze the effect of the above mentioned variables (surgical method, administration of corticosteroid, handedness etc.) on the risk of developing CMS the investigators will perform univariate and multivariate regression analyses as well as standard descriptive analyses. These analyses will be performed using R.

Discussion:

The study will be the largest prospective multicenter study on cerebellar mutism syndrome to date, and the first one of its kind to systematically gather detailed information about 1) the surgical approaches least likely to cause the syndrome, 2) how the syndrome is best treated, 3) the role of genetics and 4) differences in incidence and clinical course of the syndrome for different patients.

The ultimate aim of the study is to reduce the incidence and improve the treatment of cerebellar mutism syndrome and lead to harmonization of the treatment of CNS tumour patients across the Nordic countries.

A blood sample from each patient will be collected in order to make SNP analyses on the DNA to explore the role of genomic variants on the development, severity and recovery from the CMS.

Cerebellar Mutism Syndrome Study

Nordic Study of the Cerebellar Mutism Syndrome in Children With Brain Tumours of the Posterior Fossa

The development of CMS is determined by a survey developed Robertson et al. The correlation between the risk of developing CMS and different neurosurgical techniques, genomic variants, treatments, tumor types, comorbidities, neuroradiologic findings, handedness and preoperative language status will be explored.

Speech production that is severely reduced and limited to single words or short sentences which can only be elicited after vigorous stimulation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effects of the Prone and the Sitting Positions on the Brain Oxygenation in Posterior Fossa Surgery	NCT02933749	Infratentorial ...	SctO2 BIS	18 Years - 70 Years	Istanbul University
The Effect of Different Ventilation Strategies on Cerebral Oxygenation Using Near Infrared Spectroscopy (NIRS) in Pediatrics Undergoing Posterior Fossa Tumor Surgery	NCT04232059	Infratentorial ... Hyperventilatio... Craniotomy	cerebral oximet...	1 Year - 6 Years	Kasr El Aini Hospital
A New Approach in Intensive Care Unit Consciousness Assessment: FIVE Score	NCT06036732	Postoperative I... Postoperative I... Supratentorial ... Infratentorial ... Arnold Chiari M... Subarachnoid He... Traumatic Brain... Epilepsy, Tempo... Cerebrovascular... Intensive Care ... Coma Unconsciousness Assessment, Sel...		18 Years - 80 Years	Istanbul University - Cerrahpasa (IUC)
Effects of the Prone and the Sitting Positions on the Brain Oxygenation in Posterior Fossa Surgery	NCT02933749	Infratentorial ...	SctO2 BIS	18 Years - 70 Years	Istanbul University
Cerebellar Mutism Syndrome Study	NCT02300766	Infratentorial ... Mutism		- 18 Years	Rigshospitalet, Denmark
The Effect of Different Ventilation Strategies on Cerebral Oxygenation Using Near Infrared Spectroscopy (NIRS) in Pediatrics Undergoing Posterior Fossa Tumor Surgery	NCT04232059	Infratentorial ... Hyperventilatio... Craniotomy	cerebral oximet...	1 Year - 6 Years	Kasr El Aini Hospital

Spots Global Cancer Trial Database for infratentorial neoplasms