Cognition and Functional Connectivity After Elective Treatment of Brain Aneurysms

Study Overview
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Brief Summary
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The aim of this proposal is to investigate the effects of uneventful microsurgical and endovascular treatment of unruptured saccular non-giant anterior communicating artery [ACoA] aneurysms on resting state functional connectivity levels of higher order cognitive networks and to correlate the connectivity levels of these networks with neuropsychological performance and functional outcome. This study compares two treatment groups and one control group.

Detailed Description
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The aim of this proposal is to investigate the effects of uneventful microsurgical and endovascular treatment of unruptured saccular non-giant anterior communicating artery [ACoA] aneurysms on resting state functional connectivity levels of higher order cognitive networks and to correlate the connectivity levels of these networks with neuropsychological performance and functional outcome. The investigators' hypothesis is that the functional connectivity of various cognition networks, i.e. cognitive control network, emotion control of cognitive networks, and working memory networks, as assessed by resting state functional magnetic resonance imaging [rsfMRI], can be impaired after uneventful microsurgical and endovascular treatment of unruptured ACoA aneurysms and can be correlated with neuropsychological performance. The investigators propose to investigate 38 patients harboring unruptured ACoA aneurysms and 19 healthy controls over a 36 (until 48) months period. Patients and healthy controls will undergo baseline structural MRI, task fMRI, rsfMRI, and baseline neuropsychological examinations prior as well as 2 months after either microsurgical or endovascular aneurysm treatment or baseline examinations, respectively. Furthermore all subjects will undergo additional neuropsychological examinations 12 months after baseline examination or long-term recovery from microsurgical and endovascular treatment, respectively. The research question is of substantial importance for this patient population, since it is currently incompletely understood how the minor structural brain tissue damages seen after both treatment methods of unruptured ACoA aneurysms translate into the observed neuropsychological deficits - which are often subtle and transient in nature but still insufficiently explained on grounds of morphology and structural connectivity alone. The sensitivity of rsfMRI to depict the functional communication of spatially remote brain regions presents a novel opportunity to investigate these deficits on a whole brain scale by mapping resting state functional connectivity in higher order cognition networks that are thought to be endangered by events related to both microsurgery and embolization. Correlating these data seems promising for several reasons. First, functional connectivity analysis could be correlated with the neuropsychological impairment in various neuropsychiatric disorders and in ischemic stroke. Ischemic damage to the territories supplied by ACoA perforating arteries is involved in many cases of postoperative neuropsychological impairment after ACoA aneurysm treatment. Second, neuropsychological evaluations have become increasingly incorporated into the standard of care in the postoperative follow-up of cerebral aneurysm patients. RsfMRI could serve as a novel adjunct to neuropsychological outcome assessment. Third, the results could add relevant information to the general perception of the role of frontal lobe and forebrain damage in the pathophysiology of neurocognitive impairment. This could have an impact on neurorehabilitation programs to improve neurocognitive outcome and quality of life in this patient population. Forth, the correlation of validated neuropsychological tests with the functional connectivity rsfMRI data would further enhance the role of rsfMRI in neuroscience and its clinical use.

Official Title
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Cognition and Functional Connectivity After Elective Treatment of Brain Aneurysms

Conditions
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Aneurysm

Intervention / Treatment
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* Procedure: Clipping
* Procedure: Coiling


Participation Criteria
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Eligibility Criteria
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Intervention Groups: Inclusion criteria Male or female patients aged > 18 years Microsurgical or endovascular treatment of unruptured, saccular, non giant ACoA aneurysm Right-handedness Compliance (the patients have to be able to lay motionless in a 3 Tesla MR scanner and to cooperate with the examiner during the examination) Willingness and competence to sign informed consent form German native speaker Exclusion criteria Ruptured ACoA aneurysm Previous history of intracranial hemorrhage or serious head injury Non-saccular aneurysm [i.e. dissecting, fusiform, mycotic, traumatic] Psychiatric or neuropsychological impairment prior to aneurysm treatment Current use of any psychotropic drugs except aneurysm treatment related medication Severe visual or auditory impairment Current pregnancy or breast feeding Metallic implants [other than aneurysm clips or coils detailed in the Ethics section] or other contraindications to MRI Healthy controls: Inclusion criteria Male or female subjects aged > 18 years Right-handedness Compliance [the patients have to be able to lay motionless in a 3 Tesla MR scanner and to cooperate with the examiner during the examination] Willingness and competence to sign informed consent form German native speaker Exclusion criteria Major concurrent or previous medical or neurological illness Major concurrent or previous psychiatric Axis I disorder according to DSM-5 Clinically significant abnormal values in laboratory screening or general physical examination Current use of any psychotropic drugs Previous history of intracranial hemorrhage, serious head injury Previous or current substance abuse [except nicotine and caffeine] Severe visual or auditory impairment Current pregnancy or breast-feeding Metallic implants or other contraindications to MRI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Clipping<br>Clipping of an aneurysm of the anterior communicating artery - A titan clip will be placed round the aneurysm neck to exclude the aneurysm from the bloodflow and prevent fatal subarachnoidal hemorrhage. Patients will undergo baseline structural MRI, task fMRI, rsfMRI, and baseline neuropsychological examinations prior as well as 2 months after microsurgical aneurysm treatment. Furthermore the patients will undergo additional neuropsychological examinations 12 months after long-term recovery from microsurgical treatment. | Procedure: Clipping<br>* During the microsurgical operation a titan clip will be placed round the aneurysm neck to exclude the aneurysm from the bloodflow and prevent fatal subarachnoidal hemorrhage.<br>* Other names: microsurgical aneurysm clipping;|
| Coiling<br>Coiling of an aneurysm of the anterior communicating artery - Using a catheter technique the aneurysm dome will be filled up with coils to prevent subarachnoidal hemorrhage. Patients will undergo baseline structural MRI, task fMRI, rsfMRI, and baseline neuropsychological examinations prior as well as 2 months after endovascular aneurysm treatment. Furthermore the patients will undergo additional neuropsychological examinations 12 months after long-term recovery from endovascular treatment. | Procedure: Coiling<br>* Using a catheter technique the aneurysm dome will be filled up with coils to prevent subarachnoidal hemorrhage.<br>* Other names: endovascular treatment of brain aneurysms;|
| Healthy Controls<br>Healthy controls will undergo baseline structural MRI, task fMRI, rsfMRI, and baseline neuropsychological examinations prior as well as 2 months after baseline examinations. Furthermore all subjects will undergo additional neuropsychological examinations 12 months after baseline examination. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prefrontal neuronal functional integration measured with fMRI |  | Changes pre- vs. posttreatment after 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prefrontal executive functioning measured with neuropsychological tests |  | Changes pre- vs. posttreatment after 2 months (short-term outcome) and after 12 months (long-term outcome). | 
| Correlation of changes on neuropsychological (executive functioning) and neuronal level (fMRI). |  | Changes pre- vs. posttreatment after 2 months measured with fMRI correlated with changes in neuropsychological tests after 2 months (short-term outcome) and after 12 months (long-term outcome). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aneurysm, cognition, functional connectivity, frontal lobe function, neuropsychological testing, coiling, clipping