Clinical trial NCT03791996: Cranioplasty Cognitive Outcome Study
Official title: Impact of Cranioplasty on Cognitive Outcome: A Multi-Center Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cognitive Impairment
Brain Herniation
Keywords: Cranioplasty
Craniectomy
Cognitive impairment
Syndrome of the trephined
Lead sponsor: Kwong Wah Hospital
Sponsor class: OTHER
Collaborators: name: The Queen Elizabeth Hospital
name: Queen Mary Hospital, Hong Kong
name: Prince of Wales Hospital, Shatin, Hong Kong
name: Princess Margaret Hospital, Canada
name: Tuen Mun Hospital
name: Pamela Youde Nethersole Eastern Hospital
First posted: 2019-01-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: 3-months
measure: Neurobehavioural Cognitive State Examination (NCSE)
timeFrame: 3-months
measure: Rivermead Behavioural Memory Test (RBMT)
timeFrame: 3-months
Secondary outcomes:
measure: Motor assessment
timeFrame: 3-months
measure: Modified Functional Ambulation Category (MFAC)
timeFrame: 3-months
measure: Quality of life assessment
timeFrame: 3-months
measure: Psychological assessment
timeFrame: 3-months
measure: Caregiver assessment
timeFrame: 3-months
measure: Caregiver
timeFrame: 3-months
measure: MRI cerebral perfusion assessment
timeFrame: 3-months
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Kwong Wah Hospital
state: Hong Kong
Study officials:
affiliation: Neurosurgery, Queen Elizabeth Hospital
name: Calvin Mak, MBBS FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.