Cranioplasty Cognitive Outcome Study

Study Overview
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Brief Summary
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This will be a multicenter prospective randomized study of adult patients with an acquired skull defect as a result of craniectomy and considered suitable for cranioplasty, i.e. reconstruction of the skull defect, at all seven Hong Kong Hospital Authority neurosurgical units. Patients that underwent their primary craniectomy operation at any of the Hospital Authority neurosurgery centers from the 1st March 2019 and considered suitable for cranioplasty will be included in this study. Those who underwent their primary craniectomy before 1st March 2019 or at an institution other than the aforementioned neurosurgical units will be excluded. Data from clinical records, operation notes, medication-dispensing records, laboratory records and radiological reports will be collected. 30 adult patients with craniectomy will be recruited and randomized into two groups: early cranioplasty, i.e. performed within 3 months of craniectomy, and late, i.e. cranioplasty performed more than 3 months after the operation. The aim of the study is to determine whether early cranioplasty can improve on patient's cognitive performance compared to those who undergo the procedure after 3 months.

Detailed Description
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Decompressive craniectomy, a neurosurgical procedure where a portion of the skull calvarium is removed, is a life-saving procedure. The complication rate of cranioplasty, a neurosurgical procedure where the acquired skull defect is reconstructed, ranges from 11% to 26% and includes postoperative hemorrhage and infection. (4) The syndrome of the trephined is a recognized long-term complication in which certain groups of patients, experience debilitating neurocognitive deficits in addition to chronic headache, dizziness, fatigability and clinical depression. (2) It is believed that the lack of an overlying bone may cause undue significant atmospheric pressure on the underlying cortex, thereby reducing cerebral perfusion and cerebrospinal fluid flow. There are reports that cognitive improvement can be observed in up to 30% of patients after cranioplasty yet the underlying mechanism for this observation is unclear. (1) Some studies have demonstrated enhanced cerebral perfusion by non-invasive investigations, but there is a lack of large scale systematically performed studies to verify such cerebral hemodynamic effects. (1-3) Clinical equipoise exists regarding the optimum timing of cranioplasty procedures after craniectomies. While the anecdotal practice of delaying cranioplasty for at least 3 months after a craniectomy is common, local and overseas observational studies suggest that performing early cranioplasties (i.e. within 3 months) is equally safe in terms of infection and other operative complications. (4-6)

Official Title
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Impact of Cranioplasty on Cognitive Outcome: A Multi-Center Prospective Randomized Study

Conditions
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Cognitive Impairment, Brain Herniation

Intervention / Treatment
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* Procedure: Early cranioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years-old, Craniectomy was performed due to head injury, infarct or spontaneous intracerebral hemorrhage, and benign tumors. Craniectomy skull defect size of >10cm at its longest diameter Craniectomy performed at any of the Hospital Authority's Neurosurgical Centers after 1st March 2019 Exclusion Criteria: Age older than 80 years-old, Patients cannot communicate by obeying simple command, Patients who are unfit for cranioplasty as decided by the treating neurosurgeon Posterior fossa craniectomy Craniectomy performed before 1st March 2019 Craniectomy performed at an institution outside the Hospital Authority Any pre-existing illness that renders the patient moderately or severely disabled before the brain insult. Patients that need an additional procedure e.g. cerebrospinal fluid shunting with cranioplasty in the same setting. History of central nervous system infection Craniectomy-related complications such as hemorrhage or surgical site infection requiring surgical intervention or deemed to affect patient's long-term cognitive outcome Claustrophobia or any other medical condition that prohibits the patient from undergo MRI scanning Patients who cannot understand spoken English or Chinese

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2-arm randomised study with subjects centrally randomised by assigning them into either the control late cranioplasty group or the intervention early cranioplasty group. All subjects will eventually receive the cranioplasty procedure.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Late cranioplasty<br>Subjects undergoing cranioplasty within 3 months after craniectomy. | |
| Experimental: Early cranioplasty<br>Subjects undergoing cranioplasty beyond 3 months after craniectomy. | Procedure: Early cranioplasty<br>* Subjects undergoing cranioplasty beyond 3 months after craniectomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MOCA) | Minimum (worse): 0/30; Maximum (best) 30/30. Higher values represent a better outcome. | 3-months | 
| Neurobehavioural Cognitive State Examination (NCSE) | Multi-domain assessment involving: orientation, attention, registration, comprehension, repetition, naming, construction, calculation, similarities,judgement. Stratification of each domain into mild, moderate and severe impairment. The higher the number the better the outcome. | 3-months | 
| Rivermead Behavioural Memory Test (RBMT) |  | 3-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor assessment | Medical Research Council limb power | 3-months | 
| Modified Functional Ambulation Category (MFAC) | 7 ordinal scale assessment. The lower the scale, the worse the ambulatory ability of the patient. I: bed bound; 2: wheel-chair bound; 3: dependent walker; 4: Assisted walker; 5: Supervised walker; 6: Indoor walker; 7: Outdoor walker (patient can walk anywhere). | 3-months | 
| Quality of life assessment | Short Form-36 (SF-36) | 3-months | 
| Psychological assessment | Beck depression inventory (BDI) | 3-months | 
| Caregiver assessment | Caregiver Strain Index | 3-months | 
| Caregiver | Caregiver self-assessment questionnaire | 3-months | 
| MRI cerebral perfusion assessment | Cerebral blood flow | 3-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cranioplasty, Craniectomy, Cognitive impairment, Syndrome of the trephined