Infra- and Supratentorial Neuromonitoring in Patients With Posterior Fossa Lesions: DUAL-ICP Trial
Phase: NA
Conditions: Intracranial Pressure Increase, Posterior Fossa Lesion, Posterior Fossa Hemorrhage
Sponsor: Medical University Innsbruck

 
 STUDY PROTOCOL 
DUAL ICP STUDY  
Intracranial Supra- and Infratentorial Multimodal Neuromonitoring 
 
 
 
Project-no.: [NCH -11112018] 
Version [2.0], [April 4th, 2019] 

 
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CONTENT 
Content.............................................................................................................................................................................................. 1 
Abstract............................................................................................................................................................................................. 3 
Project collaborators – Co – Investigators - Funding.................................................................................................... 4 
Project Collaborators ............................................................................................................................................................. 4 
Department of Neurosurgery ........................................................................................................................................ 4 
Principal Investigator ....................................................................................................................................................... 4 
Internal Co-Investigators ................................................................................................................................................ 4 
External Co-Investigators................................................................................................................................................ 5 
Sponsor ........................................................................................................................................................................................ 5 
Introduction and Goals............................................................................................................................................................... 6 
Background ................................................................................................................................................................................ 6 
HISTORY ...................................................................................................................................................................................... 8 
PRESENT ...................................................................................................................................................................................10 
AIMS OF THE STUDY............................................................................................................................................................11 
Questions...................................................................................................................................................................................13 
Hypotheses...............................................................................................................................................................................13 
Clinical Relevance.............................................................................................................................................................13 
Study Design .................................................................................................................................................................................14 
METHODS..................................................................................................................................................................................14 
Variables and Parameters..................................................................................................................................................15 
Intervention/Examination.................................................................................................................................................15 
Instruments.........................................................................................................................................................................16 
Dissemination ..............................................................................................................................................................................17 
Study Population (Specimen / Test Person / Patients).............................................................................................18 
In- and Exclusion Criteria...................................................................................................................................................18 
Inclusion Criteria ..............................................................................................................................................................18 

 
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Exclusion Criteria..............................................................................................................................................................18 
Informed Consent of Test Persons / Patients............................................................................................................18 
Calculation of the NumBer of Cases...............................................................................................................................19 
Analysis...........................................................................................................................................................................................20 
Statistical Analysis.................................................................................................................................................................20 
Privacy.............................................................................................................................................................................................21 
Ethic Comittee..............................................................................................................................................................................22 
Literature - References ............................................................................................................................................................23 
 

 
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ABSTRACT 
 
Invasive neuromonitoring of intracranial pressure (ICP) is an important element of 
neurosurgical critical care that is used primarily as an indicator of adequate cerebral perfusion in 
patients, when clinical observation is not an option. Due to the constraint in size and the critical 
structures within the posterior fossa, detection of intracranial pressure particularly in the 
postoperative phase has been deemed desirable in patients with surgery in this region, particularly 
in those subjected to prolonged procedures and critical care.  
 
The posterior fossa is an anatomically constricted compartment with narrow spaces and 
intracranial hypertension quickly leads to brainstem damage and neurological dysfunction. ICP in 
the supratentorial space not necessarily correlates with ICP in the infratentorial space. Some 
authors claim that it would be beneficial to measure ICP in infratentorial space after posterior 
fossa surgery in some cases.  
 
In patients whose neurological examination results may be inconclusive or limited, it is 
valuable to have a reliable alternative method of evaluation. It is generally accepted that 
continuous ICP monitoring is very important to determine the timing of surgery and to prevent 
secondary brain damage caused by increased ICP. 
 
In t The relationship between the intracranial pressure (ICP) profiles in the supratentorial 
and infratentorial compartments remain unclear. After a neurosurgical operation in the posterior 
fossa there are most likely pressure differences between supra- and infratentorial spaces. It is well 
known that the pressure within the skull is unevenly distributed, with appreciable ICP gradients. 
To rely on autonomic changes or neurological deterioration as signs of a postoperative 
complication narrows the temporal margin of safety for the institution of treatment.  
 
It has been the policy of our Department to electively monitor all complex posterior fossa 
procedures via a supratentorial intracranial multimodal monitoring; however, it remains unclear 
whether an acute change in the posterior fossa would be reflected by the supratentorial monitor 
prior to clinical deterioration.  
 
Thus, we intend to apply the intracranial multimodal monitoring in both infratentorial and 
supratentorial compartments simultaneously. Such coincident measurements most likely will be 
the most sensitive way to assess focal swelling, ischemia and tissue perfusion, or other relevant 
complications in the posterior fossa structures.  
 
The goal of this study is to test whether direct infratentorial monitoring is a more 
efficacious method for detecting dynamic changes in the operative compartment and whether it is 
safe, in view of the critical structures within the region. In particular, the motivation behind this 
study is also to determine the value of ICP and brain tissue oxygenation monitoring (LICOX) in 
the infratentorial compared to the supratentorial space in patients with posterior fossa lesions. We 
aim to immediately detect any pertinent complications that are related to mass effect or swelling 
within the posterior fossa, resulting in subsequent prompt therapeutic intervention in these 
patients. With this in mind, postoperative multimodal neuromonitoring is a standard procedure at 
our intensive care unit. The additional intracranial infratentorial monitoring most likely is the 
most sensitive way to detect any relevant complications or lesions that may result in irreversible 
sequelae.    
 

 
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PROJECT COLLABORATORS – CO – INVESTIGATORS - FUNDING 
PROJECT COLLABORATORS 
DEPARTMENT OF NEUROSURGERY 
Medical University Innsbruck 
MZA - Medical Center Anichstrasse 
Anichstrasse 35   
6020 Innsbruck 
Austria 
PRINCIPAL INVESTIGATOR 
PD Dr. Ondra Petr, PhD 
Consultant – Faculty/Staff 
Department of Neurosurgery 
Medical University Innsbruck 
MZA - Medical Center Anichstrasse 
Anichstrasse 35 
6020 Innsbruck, Austria 
Tel: +43 (0)512 504 81286 
@: ondra.petr@tirol-kliniken.at 
Mayo Research Collaborator 
Department of Neurologic Surgery 
Mayo Clinic, Rochester, Minnesota, U.S. 
INTERNAL CO-INVESTIGATORS 
Prof. Dr. C. Thomé  
– Department of Neurosurgery (chairman) Study-Coordinator 
Dr. W. Ho  
– Department of Neurosurgery 
Study-Coordinator 
Dr. A. Görke 
– Department of Neurosurgery 
Study-Coordinator 
Dr. S. Tülü 
– Department of Neurosurgery 
 
Dr. D. Pinggera  
– Department of Neurosurgery 
Dr. K. Brawanski 
– Department of Neurosurgery 
Dr. N. Kögl 
– Department of Neurosurgery 
Dr. A. Mehmeti 
– Department of Neurosurgery 
 
Prof. Dr. R. Beer  
– Department of Neurology 
PD Dr. R. Helbok  
– Department of Neurology 
Univ.Doz. Dr. B. Pfausler  
– Department of Neurology 
 
PD Dr. S. Jochberger 
– Department of Anesthesiology  
Dr. M. Luger 
– Department of Anesthesiology  
Dr. L. Petrová 
– Department of Anesthesiology  
 
Ass. Prof. Dr. B. Glodny  
– Department of Radiology 
Prof. Dr. E. Gizewski  
– Department of Neuroradiology (chairman) 
Ass. Prof. Dr. A. Grams  
– Department of Neuroradiology (vice-chairman) 
 

 
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EXTERNAL CO-INVESTIGATORS 
 
Prof. Dr. D. Netuka, PhD 
– Department of Neurosurgery, Military University Hospital Prague  
(vice-chairman) 
 (Czech Republic) 
 
 
SPONSOR 
Department of Neurosurgery  
Medical University Innsbruck 
MZA - Medical Center Anichstrasse 
Anichstrasse 35   
6020 Innsbruck 
Austria 
 
 
SIGNATURELIST OF STUDY-COORDINATORS 
 
 
 
 
  
 
 
 
 
 
 
 
 
PD. Dr. Ondra Petr, PhD  
 
 Date  
 
 
 
 
 
 
Prof. Dr. C. Thomé  
 
 Date  
 
 
 
 
 
Dr. W. Ho  
 
 Date  
 
 
 
 
 
Dr. A. Görke  
 
 Date  
 
 
 
 

 
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INTRODUCTION AND GOALS 
BACKGROUND 
 
CRANIAL LESIONS IN THE POSTERIOR FOSSA AND INTRACRANIAL 
MULTIMODAL NEUROMONITORING  
 
Invasive neuromonitoring of intracranial pressure (ICP) is an important element of 
neurosurgical critical care that is used primarily as an indicator of adequate cerebral perfusion in 
patients, when clinical observation is not an option. Due to the constraint in size and the critical 
structures within the posterior fossa, continuous detection of postoperative pressures has been 
deemed desirable in patients with surgery in this region, particularly in those subjected to 
prolonged procedures and critical care.  
 
The posterior fossa is an anatomically constricted compartment with narrow spaces and 
intracranial hypertension quickly leads to brainstem damage and neurological dysfunction. ICP in 
the supratentorial space not necessarily correlates with ICP in the infratentorial space. Some 
authors claim that it would be beneficial to measure ICP in infratentorial space after posterior 
fossa surgery in some cases.  
 
In patients whose neurological examination results may be inconclusive or limited, it is 
valuable to have a reliable alternative method of evaluation. It is generally accepted that 
continuous ICP monitoring is very important to determine the timing of surgery and to prevent 
secondary brain damage caused by increased ICP.1, 2 
In t 
There have been few clinical studies in which simultaneous pressures were recorded 
above and below the tentorium in patients with intracranial pathology. Smyth and Henderson3 
found a lower lumbar pressure in 8 of 33 patients with intracranial space-occupying lesions, most 
of which were tumors, but the maximum difference in pressure was 100 mmH20. Yet, these 
findings together with a statement by Evans:4 “We now know as a result of many observations 
that there is a close correspondence between the ventricular and lumbar pressures under almost all 
circumstances” contrast with the high incidence of transtentorial herniation demonstrated post-
mortem in patients with brain tumors.5 
Developing and improving methods to monitor patients with posterior fossa lesions and 
to evaluate efficacy of treatment are essential. These include neuroimaging as well as intracranial 
multimodal neuromonitoring, mostly placed in the supratentorial compartment.  
The relevance of infratentorial neuromonitoring remains largely unclear. So far, the 
placement of ICP probes in the posterior fossa seems to carry very low morbidity. Furthermore, 
to rely on autonomic changes, neurological deterioration, or measurements of only the 
supratentorial compartment as a sign of relevant complications in the posterior fossa highly 
narrows the temporal margin of safety for the institution of treatment. Comprehensive evaluation 
of possible risks of posterior fossa lesions and their treatments is crucial. Of note, immediate 
detection of treatment-related complications is often challenging, still being able to avoid 
permanent neurological sequelae. The application of the advanced neuromonitoring in the 
posterior fossa may be supportive in achieving this difficult goal and may provide objective 
assessments of procedure-related complications.  

 
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Therefore, the data generated by the above-mentioned method can be expected to be 
beneficial in individualized treatment plans. 
It is a relatively novel approach to intracranial multimodal neuromonitoring. The 
application of infratentorial probes offers potential for better understanding of lesion maturation 
and progression, clinical deterioration, and monitoring the effect of treatments.  
 
We hypothesize that additional multimodal infratentorial neuromonitoring will be of high 
clinical value detecting any relevant complication and giving detailed insight in 
pathophysiological interactions in posterior fossa lesions.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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HISTORY 
 
In the late 19th century, a widespread interest evolved in the problem of cerebral 
compression and the etiology of neurological deficits induced by an expanding intracranial mass. 
As methods were developed for recording intracranial and intraspinal pressure and for the 
experimental production of acute intracranial hypertension, it was observed by some 
investigators6-10 that increased pressure was not transmitted consistently from the intracranial to 
the intraspinal space.  
 
With regard to communication of pressure within the brain, von Bergmann11 was the first 
as early as 1885 to conclude from experimental studies that the brain does not transmit pressure 
equally in all directions. In 1901, Cushing7 stated that the pressure exerted by an intracranial 
foreign body "is not transmitted equally throughout the cerebral chamber, and in consequence the 
circulatory embarrassment in corresponding degrees is unevenly felt." He also affirmed that 
severe effects of compression could occur locally with little or no transmission to remote areas of 
the brain. Meyers8  also found such a differential with injection of Ringer's lactate into the lateral 
ventricle, but the gradients of pressure illustrated in these papers were relatively small. More 
recently, Kahn9 produced experimental increased intracranial pressure by perfusion of distilled 
water into the common carotid artery and found that a differential of pressure developed between 
the supratentorial space and the posterior fossa. Penn12 and Leech and Miller13 also found such a 
differential with injection of Ringer's lactate into the lateral ventricle, but the gradients of 
pressure illustrated in these papers were relatively small. 
 
Clinical interest in the transmission of increased intracranial pressure developed as a 
result of the demonstrated importance of transtentorial herniation causing rapid neurological 
deterioration and death in patients with a space-occupying intracranial mass. This was 
reemphasized by Finney and Walker.5 They found evidence of transtentorial herniation in 55.4% 
of an unselected series of brain tumor autopsies, including an incidence of 88% in glioblastomas 
of the cerebral hemisphere. In 23% of supratentorial tumors herniations of both tentorial incisura 
and foramen magnum were present.  
 
Clarifying the high incidence of transtentorial herniation, Langfitt et al10 postulated that 
since communication of pressure from the supratentorial space to the posterior fossa is dependent 
upon patency of the basal cisterns surrounding the brain stem in the tentorial incisura, an early 
manifestation of obstruction of the incisura is the development of a differential of pressure 
between the supratentorial and infratentorial spaces. 
 
In their initial experiments10 a balloon was placed in the extradural space in the posterior 
fossa in order to create a space-occupying mass, but with gradual inflation of the balloon 
stripping of the dura mater from the skull over the transverse sinus occurred, and the balloon 
expanded into the supratentorial space. Therefore, the infratentorial balloon was inserted in the 
subdural space over the lateral and inferior aspects of the cerebellum.  
 
It is worthy of notice that a failure of communication of pressure from the infratentorial 
to the supratentorial space then occurred with inflation of the balloon. With small volumes of the 
balloon the intracerebral pressure was elevated to several times the subarachnoidal pressure over 
the corresponding cerebral hemisphere, and communication of pressure to the subarachnoidal 
space occurred gradually as the intracerebral mass was enlarged with additional injections. In 
contrast, transmission of pressure from the subarachnoidal space through the brain to the 
intracerebral balloon was invariably complete and virtually instantaneous. 

 
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In prior experiments14-16 performed by the Philadelphia group in which sustained 
increased intracranial pressure was produced by a gradually expanding extradural mass, the 
pressure within the extradural mass was equal to the pressure in the opposite extradural space in 
some animals, whereas in others it was many times the contralateral extradural pressure. This 
demonstrated that the dura mater can restrain significantly the expansion of an extradural mass 
and prevent transmission of pressure from the mass to the underlying brain.14 Likewise, it was 
found that a progressive failure of communication of pressure from the supratentorial to the 
infratentorial space occurs as cerebral tissue obstructs the tentorial incisura, and herniation of the 
cerebellar tonsils into the foramen magnum prevents transmission of pressure from the posterior 
fossa to the spinal canal.10 Thus, in these circumstances the brain does not transmit increased 
intracranial pressure.10 
 
With the gradual expansion of an extradural mass, transmission of pressure from the mass 
to the brain is dependent upon the firmness of attachment of the dura mater to the inner table of 
the skull, its configuration in relation to the underlying brain, and its physical properties.17 
 
In the past, recording of ventricular fluid pressure has proved to be a reliable method in 
clinical neurosurgery, as shown by Lundberg et al.18-20 Furthermore, some authors recorded 
supratentorial pressure during posterior fossa surgery with the intention of obtaining continuous 
information on the pressure state in major intracranial compartment.3, 21, 22 
 
Of note, some surgeons were reluctant to introduce direct subdural posterior fossa 
monitors for a number of reasons. Some of the possible problems may include cerebrospinal fluid 
(CSF) leaks, cranial nerve dysfunction, and the possibility of brainstem irritation with resulting 
autonomic dysfunction. Yet, many recent studies have showed the safety and feasibility of 
intracranial monitoring in the posterior fossa.1, 21, 23-26  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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PRESENT 
 
With regards to pathophysiology and clinical practice, the intracranial pressure (ICP) 
profiles in the supratentorial and infratentorial compartments remain unclear. After a 
neurosurgical operation in the posterior fossa there are most likely pressure differences between 
supra- and infratentorial spaces.27 It is well known that the pressure within the skull is unevenly 
distributed, with demonstrated ICP gradients.25 By contrast, Rieger et al23 reported no significant 
differences between supratentorial and infratentorial ICP values in an animal model. The 
infratentorial ICP elevation in the presented pig model led to a uniform ICP elevation in the 
intracranial space without development of a considerable pressure gradient below and above the 
tentorium. Importantly, in the low pressure part of the ICP curve, cerebrospinal fluid connects the 
compartments and contributes to the pressure equilibrium.  
 
To rely on autonomic changes or neurological deterioration as signs of a postoperative 
complication narrows the temporal margin of safety for the institution of treatment.  
 
It has been the policy of our Department to electively monitor all complex posterior fossa 
procedures via a supratentorial intracranial multimodal monitoring; however, it remains unclear 
whether an acute change in the posterior fossa would be reflected by the supratentorial monitor 
prior to clinical deterioration.  
 
Thus, we intend to apply the intracranial multimodal monitoring in both infratentorial and 
supratentorial compartments simultaneously. Such coincident measurements most likely will be 
the most sensitive way to assess focal swelling, ischemia and tissue perfusion in the posterior 
fossa structures.  
 
Importantly, the benefits of intracranial pressure (ICP) monitoring must be weighed 
against the associated risks and complications. The risks of ICP monitoring are related to the 
degree of invasiveness, the location of the device, the presence of systemic infections, the need to 
restrict patient movement, and monitoring drift or artificially low readings. Complications include 
infection, hematomas, epilepsy, cerebral puncture, cranial nerve palsies, and CSF leaks. In 
general, the incidence of complication has been quoted as from 1.1% to 7.7%.28-32 
A major motivating factor in our routine use of postoperative ICP monitoring is that 
clinical parameters (for example, blood pressure, neurological status, pulse, and respiration) are 
not always reliable markers of increased ICP or impending neurological deterioration secondary 
to complications.10, 33 Moreover, some authors have showed the safety of ICP monitoring in the 
posterior fossa.1, 21, 23-26   
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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AIMS OF THE STUDY 
 
The goal of this study is to test whether direct infratentorial monitoring is a more 
efficacious method for detecting dynamic changes in the operative compartment and whether it is 
safe, in view of the critical structures within the region. 
 
The motivation behind this study is to determine the value of ICP and brain tissue 
oxygenation monitoring (LICOX) in the infratentorial compared to the supratentorial space in 
patients with posterior fossa lesions. Our aim is also the immediate detection of any pertinent 
complications that are related to mass effect or swelling within the posterior fossa, leading to 
subsequent prompt intervention in these patients. With this in mind, postoperative multimodal 
neuromonitoring is a standard procedure at our intensive care unit. The additional intracranial 
infratentorial monitoring most likely is the most sensitive way to detect any relevant 
complications or lesions that may result in irreversible sequelae.    
 
The additional monitoring may also help to direct normal postoperative care in terms of 
ventilatory support, the use of positive end-expiratory pressures, continued osmotherapy, and 
patient positioning. Finally, in postoperative patients with a neurological deficit or in those who 
must be maintained sedated or paralyzed, ICP- and brain tissue oxygenation (LICOX) with blood 
pressure monitoring are highly reliable methods to detect potential worsening as soon as possible. 
Of note, the infratentorial and supratentorial compartments are related by conduction of fluid in 
the subarachnoid space. 
 
Under normal anatomical conditions, there is little intercompartmental difference in 
pressure between the infra- and supratentorial fossae. Surgery, brain shifts, or occlusion of the 
basilar cisterns may radically alter the equilibration of both compartmental pressures, since brain 
is a non-Newtonian fluid.33 Furthermore, the pressure and compliance within the two 
compartments are different, as indicated by aforementioned studies.7-9, 12, 13, 25 A thorough review 
of the current literature reveals little information concerning the specific risks and complications 
related to direct posterior fossa monitoring, and just fractional knowledge of ICP pathophysiology 
in the posterior fossa and relations between both supra- and infratentorial compartments.   
 
Ultimately, recent data1, 21, 23-26 strongly support the thesis that infratentorial monitoring is 
a safe technique, and most likely does not offer any greater risk than a subdural catheter located 
in the supratentorial space. In addition, the placement of the monitor within the operative site 
prevents exposing the patient to double jeopardy for infection, by avoiding a separate procedure. 
It is well known that the risk of infection is greatest at the time of introduction of any ICP 
monitoring device.  
 
 
 
 
 
 
 
 
 
 
 
 

 
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To summarize all intentions of the anticipated clinical trial we aim to: 
 
1) prove the safety and feasibility of the intracranial multimodal monitoring in the posterior 
fossa, 
2) establish the methodological use of infratentorial multimodal monitoring in patients with 
posterior fossa lesions as standard of care; 
3) gain additional information of posterior fossa pathophysiology with complementary 
monitoring of the dynamical changes; subsequently  
4) facilitate the neurointensive care of these patients including ventilatory support, the use 
of positive end-expiratory pressures, continued osmotherapy, and patient positioning; 
ultimately  
5) better understand of pathophysiological processes with 
6) immediately identify of complications with subsequent prompt intervention if needed.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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QUESTIONS 
 
* 
Is infratentorial multimodal neuromonitoring safe and feasible, and necessary? 
* 
Do data assessed by multimodal monitoring in the posterior fossa correlate with data 
from the supratentorial compartment? 
* 
Is infratentorial multimodal neuromonitoring able to timely predict complications such as 
local swelling, mass effect, vasospasm, ischemia, or infarction? 
* 
Is infratentorial multimodal neuromonitoring of value in daily clinical practice? 
 
 
HYPOTHESES 
 
! The intracranial multimodal monitoring in the posterior fossa is safe and feasible, without 
any increased risk due to additional probes.  
! Data generated by infratentorial multimodal neuromonitoring do not completely correlate 
with data from standardized supratentorial multimodal neuromonitoring. There are 
significant differences in ICP- or brain tissue oxygenation values between the 
supratentorial and infratentorial compartments.  
! The infratentorial multimodal monitoring immediately detects all relevant complications 
related to posterior fossa lesions including mass effect, local swelling, postoperative 
hematoma, ischemic events, decrease in the blood flow, vasospasm and inadvertent or 
prolonged vessel occlusion, or infarction, resulting in prompt therapeutic intervention if 
necessary. 
! Additional information from infratentorial probes facilitate to maintain the critical 
patients including ventilatory support, the use of positive end-expiratory pressures, 
continued osmotherapy, and patient positioning. 
 
 
 
CLINICAL RELEVANCE 
Our prospective study can provide better guidance and optimization of clinical therapy 
through a comprehensive assessment of patients harboring posterior fossa lesions.  
This study has very high potential to generate a new intellectual property, to yield 
discoveries improving the prediction of complications and monitoring the effects of treatments. 
The data will offer better understanding of pathophysiological mechanisms in posterior fossa 
lesions. 

 
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STUDY DESIGN 
 
METHODS 
 
In phase I of the study 15 patients with posterior fossa lesions who require prolonged 
neurointensive care and in which any intracranial invasive intervention is indicated regardless of 
used technique or treatment modality will be enrolled in the study. The indication for posterior 
fossa lesion treatment will be decided on a case-by-case basis by our neurosurgical team 
irrespective of the study. 
The study will start as a monocentric clinical trial (pilot study), and subsequently in phase 
II the study is planned to be continued as a multicentric trial.  
In the majority of patients, ICP- and LICOX sensors are usually placed in the right 
frontal lobe and/or at the site of the lesion. In case of posterior fossa surgery, additional probes 
(ICP / LICOX) will be placed into the surgical field.  
The neuromonitoring data will be recorded and analyzed. Additionally, demographic 
data, all treatment-related complications, and management of intracranial hypertension will be 
recorded.  
All adverse effects will be noted and reported, even if no clinical consequence will ensue. 
Non-neurological complications such as cardiopulmonary complications will be documented 
separately.  
After the invasive treatment of the posterior fossa lesion, all patients will undergo CT 
and/or MRI as standard of care within 72 hours after the intervention (the acute phase) as a 
protocol for detection of procedure-related complications. As standard of care, an additional 
follow-up MRI will be performed if needed. In stable patients a preoperative MRI will also be 
performed before invasive treatment 
 
The following outcomes will be evaluated and analyzed: mean ICP, ICP pulse amplitude, 
respiratory waves, slow waves and the RAP (compensatory reserve) index of supra- and 
infratentorial ICP signals, transtentorial difference, brain tissue oxygenation, blood saturation, 
ASTRUP, and further vital parameters, peri- and postoperative morbidity and mortality, 
procedure-related morbidity including infection, hematomas, epilepsy, cerebral puncture, cranial 
nerve palsies, and CSF leaks, perioperative cerebral ischemia, long-term neurological morbidity 
and mortality, and overall neurological outcome.  
Institutional review board will be obtained by the Ethics Committee of the Medical 
University Innsbruck, Austria. Informed consent will be acquired from all patients for 
participation in the study during the study period according to local requirements.  
All treatment techniques and MRIs will be performed as a part of routine clinical care and 
no modifications will be introduced in the treatment or the follow-up modalities currently used by 
the Department of Neurosurgery and Neuroradiology, with the exception of 31P- MRS (see 
above).  
 
 
 

 
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VARIABLES AND PARAMETERS 
Clinical data 
The following demographic characteristics of treated posterior fossa lesions and 
outcomes will be documented and analyzed: type, location, size, shape, volume, technical success 
of treatment, recurrence, bleeding / rebleeding, perioperative morbidity and mortality, procedure-
related morbidity including thromboembolic events, iatrogenic rupture, perioperative stroke, 
occurrence of complications related to lesion (e.g. mass effect, delayed ischemia, hydrocephalus, 
vasospasm, etc.) long-term neurological morbidity and mortality, and overall good neurological 
outcome 
 
Cerebral multimodal neuromonitoring 
ICP, brain oxygen partial pressure (PtO2) / LICOX®, alternatively microdialysis, cerebral blood 
flow / Hemedex®, cortical spreading depolarization (CSD) 
 
 
MRI (including DWI and 31P-MRS in selected cases) 
Phosphocreatin (PCr), Phosphomonoester (PME), Phosphoethanolamin (PEth), Phosphocholin 
(PCho), Phosphodiester (PDE), Glycero-Phosphocholin (GPC), Glycero-Phosphoethanolamin 
(GPE), Anorganisches Phosphat (Pi), Adenosin-Triphosphat (α, β, γ ATP), Adenosin Diphosphat 
(ADP), Mg2+, pH 
 
 
 
INTERVENTION/EXAMINATION 
All patients suffering from symptomatic posterior fossa lesions are first treated and 
stabilized in the emergency room and/or at the ICU. After the initial imaging (in most cases 
CT/CTA), if necessary, patients are transported to the OR and/or the angiosuite. After treatment, 
regardless of the used treatment modality and possibly after implementation of invasive 
multimodal neuromonitoring according to contemporary guidelines by patient impaired 
consciousness (e. g., with GCS≤8), implantation of multimodal neuromonitoring is performed – 
please find the details in the study protocol TIBI-study (AN2014-0201 339/4.6 – microdialysis, 
tissue perfusion measurement, ICP-measurement, LICOX) the patients are transported to the 
neurosurgical or neurological ICU. In each patient, MRI including 31P-MRS will be performed at 
different stages of treatment (the indication for neuroimaging will be decided on a case-by-case 
basis). As mentioned above, in stable patients a preoperative MRI will also be performed which 
may provide additional relevant information for patient treatment. 
Simultaneously, data from invasive multimodal neuromonitoring and laboratory values 
will be acquired and evaluated during the ICU stay after treatment.  
All methods are validated by an international collaborative ring trial, as they are used in 
routine.  
Finally, outcome scores like the mRS and the Glasgow Outcome Scale will be recorded.  
 

 
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INSTRUMENTS 
! Multimodal Neuromonitoring 
□ ICP-measurement, Raumedic, Münchberg, Germany 
□ Brain tissue oxygen and brain temperature, Licox, Integra, Plainsboro, New Jersey, USA 
□ Cerebral microdialysis, CMA, Stockholm, Sweden 
□ Alternatively tissue perfusion measurement, Hemedex, Cambridge, MA,USA 
 
 

 
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DISSEMINATION 
A part of this study will most likely be assigned as a clinical Ph.D.-project for the residents at the 
Department of Neurosurgery.  

 
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STUDY POPULATION (SPECIMEN / TEST PERSON / PATIENTS) 
IN- AND EXCLUSION CRITERIA 
INCLUSION CRITERIA 
□ Posterior fossa lesions with anticipated prolonged neurointensive critical care 
□ Patients older than 18 years 
□ Informed consent if applicable (unconscious patients will be also enrolled) 
□ No existing exclusion criteria  
EXCLUSION CRITERIA 
□ Coagulation disorders 
□ Age < 18 years 
□ Pregnancy 
 
 
INFORMED CONSENT OF TEST PERSONS / PATIENTS 
All patients harboring posterior fossa lesion who meet the inclusion criteria will be enrolled in the 
study.   
Informed consent will be acquired from all patients for participation in the study during the study 
period.  
All interventions and neuroimaging (e.g. MRI) will be performed as a part of routine clinical care 
and no modifications will be introduced in the treatment or the follow-up modalities currently 
used by the Department of Neurosurgery / Neuroradiology, except 31P-MRS (see above). 
 
 
 
 
 
 
 
 
 
 

 
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CALCULATION OF THE NUMBER OF CASES 
The study is designed as a prospective clinical trial (the sample of 30 patients was selected 
according to epidemiologic data and estimated annual incidence of posterior fossa lesions in 
Central Europe).  
Regarding the complex patient cohort a high drop-out rate for MRI in the acute phase due to 
unstable patients with a consecutive infeasibility of MRI is to be expected.  
 

 
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ANALYSIS 
Data collection 
Clinical and procedural data will be collected prospectively. The adverse events are 
classified in three groups, according to their mechanism: 
* 
Lesion-related events 
* 
Intraoperative / intraprocedural (iatrogenic) events 
* 
Device-related problems 
 
The outcome of adverse events is classified in four groups: 
* 
No clinical modification 
* 
Transient deficit(s)  
* 
Permanent deficit(s) (deficit(s) remaining at the 6-months follow-up) 
* 
Death 
All-cause morbidity is defined as a modified Rankin score ≥ 3. When the preoperative mRS 
was greater than 2, the all-cause morbidity is defined as any increase in the mRS value.  
 
STATISTICAL ANALYSIS 
The distribution of continuous variables will be described by using means and standard 
deviations, and discrete variables will be described as frequencies, percentages, and confidence 
intervals. The Clopper-Pearson exact method will be used to construct 95% confidence intervals 
(CIs).  
The characteristics of both treatment groups will be compared by using Chi2 test. All 
outcome results will be compared between the study groups by using a  MannWhitneyU test, or 
Student t test where appropriate. P <0.05 is considered indicative of a statistically significant 
difference.  
 

 
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LITERATURE - REFERENCES 
 
1. 
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posterior fossa hematoma]. Nihon Ika Daigaku zasshi 1990;57:334-343 
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3. 
Smyth GE, Henderson WR. OBSERVATIONS ON THE CEREBROSPINAL FLUID 
PRESSURE ON SIMULTANEOUS VENTRICULAR AND LUMBAR PUNCTURES. Journal 
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Langfitt TW, Weinstein JD, Kassell NF, et al. TRANSMISSION OF INCREASED 
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Penn RD, Lee MC, Linninger AA, et al. Pressure gradients in the brain in an 
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Langfitt TW, Shawaluk PD, Mahoney RP, et al. EXPERIMENTAL INTRACRANIAL 
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16. 
Weinstein JD, Langfitt TW, Bruno L, et al. Experimental study of patterns of brain 
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