Cranioplasty Cognitive Outcome Study

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

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.

Study Overview

• Status: Unknown
• Conditions: Cognitive Impairment; Brain Herniation
• Intervention / Treatment: Procedure: "Early" cranioplasty

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Calvin Mak, MBBS FRCS; Phone Number: 35066026; Email: mhk349@ha.org.hk
• Study Contact Backup: Name: Marina Lee; Phone Number: 35066026; Email: leeymm@ha.org.hk

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Recruiting
      • Kwong Wah Hospital
      • Principal Investigator: Peter YM Woo, FRCS (SN)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age greater than or equal to 18 years-old,
2. Craniectomy was performed due to head injury, infarct or spontaneous intracerebral hemorrhage, and benign tumors.
3. Craniectomy skull defect size of >10cm at its longest diameter
4. Craniectomy performed at any of the Hospital Authority's Neurosurgical Centers after 1st March 2019

Exclusion Criteria:

1. Age older than 80 years-old,
2. Patients cannot communicate by obeying simple command,
3. Patients who are unfit for cranioplasty as decided by the treating neurosurgeon
4. Posterior fossa craniectomy
5. Craniectomy performed before 1st March 2019
6. Craniectomy performed at an institution outside the Hospital Authority
7. Any pre-existing illness that renders the patient moderately or severely disabled before the brain insult.
8. Patients that need an additional procedure e.g. cerebrospinal fluid shunting with cranioplasty in the same setting.
9. History of central nervous system infection
10. Craniectomy-related complications such as hemorrhage or surgical site infection requiring surgical intervention or deemed to affect patient's long-term cognitive outcome
11. Claustrophobia or any other medical condition that prohibits the patient from undergo MRI scanning
12. Patients who cannot understand spoken English or Chinese

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: "Late" cranioplasty; Subjects undergoing cranioplasty within 3 months after craniectomy.
Experimental: "Early" cranioplasty; Subjects undergoing cranioplasty beyond 3 months after craniectomy.	Procedure: "Early" cranioplasty; Subjects undergoing cranioplasty beyond 3 months after craniectomy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kwong Wah Hospital
• Collaborators: Prince of Wales Hospital, Shatin, Hong Kong; Queen Mary Hospital, Hong Kong; Princess Margaret Hospital, Canada; Tuen Mun Hospital; Pamela Youde Nethersole Eastern Hospital; The Queen Elizabeth Hospital
• Investigators: Principal Investigator: Calvin Mak, MBBS FRCS, Neurosurgery, Queen Elizabeth Hospital

Publications and helpful links

General Publications

• Halani SH, Chu JK, Malcolm JG, Rindler RS, Allen JW, Grossberg JA, Pradilla G, Ahmad FU. Effects of Cranioplasty on Cerebral Blood Flow Following Decompressive Craniectomy: A Systematic Review of the Literature. Neurosurgery. 2017 Aug 1;81(2):204-216. doi: 10.1093/neuros/nyx054.
• Bender A, Heulin S, Rohrer S, Mehrkens JH, Heidecke V, Straube A, Pfefferkorn T. Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Inj. 2013;27(9):1073-9. doi: 10.3109/02699052.2013.794972. Epub 2013 May 10.
• Ashayeri K, M Jackson E, Huang J, Brem H, Gordon CR. Syndrome of the Trephined: A Systematic Review. Neurosurgery. 2016 Oct;79(4):525-34. doi: 10.1227/NEU.0000000000001366.
• Malcolm JG, Rindler RS, Chu JK, Grossberg JA, Pradilla G, Ahmad FU. Complications following cranioplasty and relationship to timing: A systematic review and meta-analysis. J Clin Neurosci. 2016 Nov;33:39-51. doi: 10.1016/j.jocn.2016.04.017. Epub 2016 Aug 4.
• Xu H, Niu C, Fu X, Ding W, Ling S, Jiang X, Ji Y. Early cranioplasty vs. late cranioplasty for the treatment of cranial defect: A systematic review. Clin Neurol Neurosurg. 2015 Sep;136:33-40. doi: 10.1016/j.clineuro.2015.05.031. Epub 2015 May 29.
• Tsang AC, Hui VK, Lui WM, Leung GK. Complications of post-craniectomy cranioplasty: risk factor analysis and implications for treatment planning. J Clin Neurosci. 2015 May;22(5):834-7. doi: 10.1016/j.jocn.2014.11.021. Epub 2015 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: December 30, 2018
• First Submitted That Met QC Criteria: December 30, 2018
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Cognitive impairment; Cranioplasty; Craniectomy; Syndrome of the trephined
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: CCO-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No