- Email: [email protected]
Case-Control Study of Cephalometrics in Patients with Moyamoya
Original Article
Case-Control Study of Cephalometrics in Patients with Moyamoya Nida Faheem1, Domenico A. Gattozzi2, Ernest J. Madarang3, Paul J. Camarata2, Gary S. Gronseth1
OBJECTIVE: To determine whether cranial metrics consistently differed between patients with moyamoya and age-, sex-, and race-matched controls.
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METHODS: Patients diagnosed with moyamoya disease by cerebral angiogram were obtained from a prospectively collected database through the Department of Neurosurgery at the University of Kansas Medical Center. Control patients matched by decade of age, sex, and race were collected through a deidentified hospital database by International Classification of Diseases-9 and 10 codes for ischemic stroke to identify patients with computed tomography angiograms. Imaging studies for both groups were analyzed to obtain 6 skull metrics: maximum anterior to posterior distance, maximum biparietal distance, bregma to occiput distance, right carotid canal diameter (CCD), left CCD, and cephalic index.
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RESULTS: Forty-five patients were identified in each cohort. Measurements of mean anterior to posterior skull diameter, mean biparietal skull diameter, bregma to occiput distances, and calculated cephalic index did not demonstrate a statistically significant difference between patients with moyamoya and control patients. Right carotid canal mean diameter was 4.8 mm for the moyamoya group and 5.4 mm for the control group, with a significant raw mean difference of L0.61 mm (95% confidence interval, L0.95 to L0.27). Left CCD was 4.7 mm for the moyamoya group and 5.5 mm for the control group, resulting in a significant raw mean difference of L0.76 mm (95% confidence interval, L1.09 to L0.43).
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Key words Carotid canal - Cephalometric - Ischemic stroke - Moyamoya - Skull -
Abbreviations and Acronyms BOD: Bregma to occiput distance BPD: Biparietal diameter CCD: Carotid canal diameter CI: Confidence interval CT: Computed tomography CTA: Computed tomography angiogram FOD: Fronto-occipital diameter
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CONCLUSIONS: This study identified 2 skull parameters as statistically different in patients with moyamoya compared with a matched control group of patients with ischemic stroke: right CCD and left CCD.
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INTRODUCTION
A
lthough Takeuchi and Shimizu1 first described a patient with bilateral hypoplasia of the internal carotid arteries in 1957, the term “moyamoya disease,” meaning a “vague or hazy puff of smoke” in Japanese, was not used until 1969, when Suzuki and Takaku2 identified a characteristic angiographic appearance of dilated, skull-base collateral arteries that form in response to brain ischemia. Moyamoya disease typically causes progressive, bilateral supraclinoid internal carotid artery (ICA) stenosis that can also involve proximal portions of the middle cerebral and/or anterior cerebral arteries. The posterior circulation is rarely involved, even in advanced cases. Small collateral vessels form from the Circle of Willis, intracranial portion of the ICA, anterior choroidal artery, and posterior cerebral arteries to communicate with the lenticulostriate or thalamoperforating arteries. This aids reconstitution of blood flow distal to the site of vessel occlusion.3 Clinically, patients experience both ischemic infarcts secondary to progressive anterior circulation stenosis and hemorrhagic infarcts related to fragility of the small, thin-walled collateral vessels.4 Although moyamoya has been identified in patients worldwide, there is a predominance of the disease in East Asian populations—specifically Japan, China, and Korea. Surveys in Japan in
HERON: Healthcare Enterprise Repository for Ontological Narration ICA: Internal carotid artery RMD: Raw mean difference From the Departments of 1Neurology, 2Neurosurgery, and 3Radiology, University of Kansas Medical Center, Kansas City, Kansas, USA To whom correspondence should be addressed: Domenico A. Gattozzi, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019) 130:e831-e838. https://doi.org/10.1016/j.wneu.2019.06.233 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
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CEPHALOMETRICS IN PATIENTS WITH MOYAMOYA
Figure 1. Examples of the cephalometrics assessed. (A) Maximum anterior to posterior diameter, (B) biparietal diameter, (C) bregma to occiput
2006, estimated an annual incidence of 0.94 patients per 100,000 population per year.5 In comparison, hospital discharge data in 2005, from the western United States reported a significantly lower incidence of 0.086 per 100,000 population per year. There is also a 2-to-1 female-to-male ratio.6 Several conditions have been strongly associated with moyamoya disease including radiotherapy of the head or neck, neurofibromatosis type 1, sickle cell anemia, and Down syndrome. Down syndrome has a 26-fold greater prevalence in patients with coexisting moyamoya disease (3760 per 100,000) compared with the prevalence of Down syndrome among live births (145 per 100,000).7,8 The question arises then if there is a shared characteristic between Down Syndrome and an East Asian racial background underlying the association with moyamoya disease. Cephalometric analyses of patients with Down syndrome have demonstrated brachycephaly with reduced anterior and posterior
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diameter, (D) carotid canal diameter (CCD), green square delineating close-up area for (E) CCD close-up.
cranial base lengths.9 This likely occurs secondary to craniosynostosis, specifically with premature ossification of the coronal suture. Restriction of the skull’s growth in the anterior and posterior directions results in brachycephaly with recessed frontal bones and a flattened occiput.10 Similarly, cephalometric analyses of East Asian and Caucasian skulls demonstrate brachycephaly with a flatter back and forehead in East Asian patients.11-13 Other observational studies have additionally noted non-craniosynostosis deformational brachycephaly in infants of predominantly supine-sleeping cultures such as Japan and Korea, as opposed to prone-sleeping Western cultures.14 We sought to delineate a consistent correlation between skull metrics and moyamoya disease, with a hypothesis that patients with moyamoya had a shorter anterior to posterior cranial diameter and decreased bregma to occiput distance (BOD) (indicative of a flatter occiput) compared with non-moyamoya
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CEPHALOMETRICS IN PATIENTS WITH MOYAMOYA
Table 1. Continued
Table 1. Background Characteristics Moyamoya
Control
Sex Male
11
11
Female
34
34
Moyamoya
Control
60e70
0
0
80e90
0
0
4
4
Male
3
3
Female
1
1
Asian Sex
Age (years) (% male) 16e19
2 (0%)
2 (0%)
20e30
22 (23%)
22 (23%)
Age (years) (% male)
40e50
16 (25%)
16 (25%)
60e70
5 (40%)
5 (40%)
16e19
0
0
0
20e30
0
0
40e50
3 (66%)
3 (66%)
60e70
1 (100%)
1 (100%)
80e90
0
0
4
4
Male
1
1
Female
3
3
80e90
0
Race White
24
24
Sex Male Female
3 21
3
Other
21
Sex
Age (years) (% male) 16e19
1 (0%)
1 (0%)
Age (years) (% male)
20e30
12 (17%)
12 (17%)
40e50
9 (11%)
9 (11%)
16e19
1 (0%)
1 (0%)
60e70
2 (0%)
2 (0%)
20e30
1 (0%)
1 (0%)
0
0
40e50
1 (0%)
1 (0%)
11
11
60e70
1 (100%)
1 (100%)
80e90
0
0
9 (20%)
8 (18%)
80e90 Black Sex Male
4
4
Diabetes
Female
7
7
Hypertension
24 (53%)
25 (56%)
Tobacco use
18 (40%)
21 (47%)
Coagulopathy
1 (2%)
2 (4%)
4 (9%)
0
38 (84%)
45 (100%)
Age (years) (% male) 16e19
0
0
20e30
7 (43%)
7 (43%)
Sickle cell disease
40e50
3 (33%)
3 (33%)
Ischemic stroke
60e70
2 (50%)
2 (50%)
Hemorrhagic stroke
8 (18%)
3 (7%)
28 (62%)
25 (56%)
0
5 (11%)
0
0
Antiplatelet use
2
2
Anticoagulation use
Male
0
0
Female
2
2
80e90 Hispanic Sex
Age (years) (% male) 16e19
0
0
20e30
2 (0%)
2 (0%)
40e50
0
0 Continues
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controls. If a statistically significantly different metric was noted, we planned to incorporate this into a scoring system for earlier identification of progressive moyamoya disease. METHODS Study Design Approval for this study was received by an institutional review board committee for ethical standards on human
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Table 2. Results Moyamoya
Controls
Measure
Mean
SD
Number
Mean
SD
Number
APD
160.143
9.004
45
161.496
9.089
45
BPD
134.039
7.244
45
132.940
7.944
45
BOD
140.098
6.076
45
141.432
4.645
45
RCC
4.802
0.861
45
5.410
0.765
45
0.764
1.093
LCC
4.693
0.899
45
5.457
0.678
45
CI%
83.887
5.521
45
82.400
5.084
45
RMD
LCL
UCL
5.092
2.384
2.042
4.240
1.334
3.568
0.901
0.608
0.944
1.354 1.099
1.487
0.706
0.271 0.435 3.680
APD, anterior-posterior diameter; BOD, bregma to occiput distance; BPD, biparietal diameter; CI, confidence interval; LCC, left carotid canal diameter; LCL, lower confidence level; RCC; right carotid canal diameter; RMD, raw mean difference; SD, standard deviation; UCL, upper confidence level.
experimentation. This study was a caseecontrol design. Patients with moyamoya were identified through a previously collected neurosurgery database at the University of Kansas Medical Center. Control patients were selected through the HERON (Healthcare Enterprise Repository for Ontological Narration) deidentified patient database with International Classification of Diseases-9 and 10 codes for ischemic stroke. Patients with ischemic stroke were
Figure 2. Scatter plot comparing cephalometric measurements between moyamoya and control populations. FOD Diam, fronto-occipital diameter;
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chosen because of the availability of computed tomography angiograms (CTAs) necessary for all skull metrics. Inclusion criteria for patients with moyamoya were as follows: patients were between the ages of 16 and 90 years, diagnosed with moyamoya disease (no distinction was made for primary or secondary moyamoya disease) by cerebral angiogram, with at least 1 CTA for the purposes of measuring cranial metrics, and at least 2 cerebral
BP Diam, biparietal diameter; BOD, bregma to occiput distance.
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ORIGINAL ARTICLE NIDA FAHEEM ET AL.
CEPHALOMETRICS IN PATIENTS WITH MOYAMOYA
Figure 3. Scatter plot comparing left and right carotid canal diameters (CCDs) between moyamoya and control populations. LCC Diam, left CCD; RCC Diam, right CCD.
angiograms to be reviewed in the second part of this study for Suzuki staging. Control patients were included if between the ages of 16 and 90 years, diagnosed with an ischemic stroke, and had at least 1 CTA for the purposes of measuring cranial metrics. Pediatric patients, patients with Down Syndrome, and those with traumatic, surgical, or other significant cranial deformity were excluded from both groups. Patients with moyamoya were sorted by sex, then decade of age (16e19, 20e30, 40e50, 60e70, and 80e90 years), and race (white, black, Hispanic, Asian, or other—with other defined as distinct from the 4 prior racial backgrounds, a mixed racial background, or unidentified). These were then matched based on sex, decade of age, and race to non-moyamoya control patients. Basic vascular risk factors including diabetes, hypertension, tobacco use, coagulopathies, ischemic stroke, hemorrhagic stroke, and sickle cell disease were assessed. Antithrombotic use at time of presentation (antiplatelet or anticoagulant use) was additionally recorded. Under instructions of a neuroradiologist, primary investigators obtained 4 cranial measurements on each patient in the moyamoya and control groups: maximum anterior to posterior diameter from inner bony mantle at the level of the nasion to inner bony mantle at the level of the inion, maximum biparietal diameter (BPD) measured from outer bony mantle bilaterally, maximum distance from bregma (visualized on sagittal CTA head as converging point of coronal and sagittal sutures) to posterior aspect of the foramen magnum at the base of the occiput, and maximum width of the carotid canal bilaterally was measured at mid-way through the transverse portion of each canal in the petrous bone (Figure 1). The measurements obtained on axial sequences (fronto-occipital diameter [FOD], BPD, carotid canal diameter [CCD]) were obtained on thin-cut computed tomography (CT) sequences with a slice thickness of 0.625 mm, with approximately 256 images in the series. The measurements obtained on sagittal sequences (BOD) were obtained on sagittal
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reconstruction of the axial images, with approximately 91 images in the series. Cephalic indices were also calculated by dividing BPD by FOD and multiplying by 100. Patients with agenesis of the carotid canal were excluded; all patients included had a measurable CCD on imaging. Average measure and standard deviation for each parameter was obtained per group. Analysis of variance was performed and the raw mean difference (RMD) of the variance, along with 95% confidence intervals (CIs), was calculated for each parameter per group. RESULTS Forty-five patients were identified in each cohort. Table 1 demonstrates background characteristics of the moyamoya and control patients. Overall, there was a greater predominance of women compared with men, with 34 women and 11 men in both moyamoya and control groups. Patients were primarily in the age group 20e30 (22 patients, 23%) years, or 40e50 (16 patients, 25%) years. Average age of the moyamoya group at presentation to the neurosurgery service was 39 years; average age of the control group was 41 years. Assessed by racial background, white patients comprised most of the moyamoya and matched controls (24 patients), followed by black (11 patients), Asian (4 patients), Hispanic (2 patients), and other (4 patients). Moyamoya and matched controls were fairly similar across the vascular risk factors, with notable differences being 4 patients with sickle cell disease in the moyamoya group—a known associated risk factor—and anticoagulant use in 5 patients in the ischemic stroke control group, whereas zero patients were on anticoagulants in the moyamoya cohort (Table 1). Mean anterior to posterior diameter for patients with moyamoya was 160.1 mm compared with 161.5 mm for the controls, with a non-significant RMD of 1.4 mm (95% CI, 5.01 to 2.38). Mean
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Table 3. Carotid Canal Diameters Associated with Moyamoya Disease Laterality
Table 3. Continued Left CCD
Affected Side
6.4
6.5
Right
6
6.1
Right
Both
4.31
4.27
Right
4.7
Both
4.5
4.3
Right
4.4
5.7
Both
3.6
3.3
Right
5.6
4.8
Both
5.1
5.3
Right
5.2
5.76
Both
3.22
5.6
Right
5.5
4.96
Both
CCD, carotid canal diameters.
4.9
4.77
Both
4.57
4.48
Both
4.14
4.37
Both
4.36
4.45
Both
2.84
2.89
Both
2.3
3.65
Both
6.19
4.77
Both
5.13
4.91
Both
4.17
4.5
Both
4.3
4.27
Both
3.5
2.95
Both
4.37
4.95
Both
4.1
4.1
Both
4.64
5.2
Both
5.62
5.7
Both
4.5
4.7
Both
5.6
5.8
Both
4.79
5.3
Both
5.8
6.3
Both
4.63
3.3
Both
4.49
4.5
Both
4.48
4.7
Both
6.02
5.4
Both
5.31
6.1
Both
5.2
5.3
Both
4.78
4.73
Left
5.85
4.62
Left
3.9
4.2
Left
3.18
3.9
Left
5.21
5.8
Left
4.8
4.8
Right
Right CCD
Left CCD
Affected Side
4.1
4.1
Both
4.2
5.5
5.2
Continues
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Right CCD
BPD for patients with moyamoya was 134.0 mm compared with 132.9 mm for the controls, with a non-significant RMD of 1.1 mm (95% CI, 2.04 to 4.24). BODs were 140.1 mm for the moyamoya group and 141.4 mm for the control group; this resulted in a nonsignificant RMD of 1.33 mm (95% CI, 3.6 to 0.90). Right carotid canal mean diameter was 4.8 mm for the moyamoya group and 5.4 mm for the control group, with a significant RMD of 0.61 mm (95% CI, 0.95 to 0.27). Left CCD was 4.7 mm for the moyamoya group and 5.5 mm for the control group, resulting in a significant RMD of 0.76 mm (95% CI, 1.09 to 0.43). Cephalic index (BPD divided by anterior to posterior distance, multiplied by 100) was 83.8% for the moyamoya group, 82.4% for the control group; this yielded a non-significant RMD of 1.5% (Table 2; Figures 2 and 3). DISCUSSION CCD Watanabe et al.15 studied the CT scans of 60 adult patients without moyamoya who obtained CT scans for other reasons (headache, trauma, etc.). They found that of the 60 unaffected non-matched adults, the bony carotid canal was on average 5.27 mm wide, whereas in their 11 reported adult patients with moyamoya it was on average 3.31 mm. In addition, they studied the CT scans of 50 pediatric patients, 10 of which were aged <2 years to trend growth and development.15 Motoshima et al.16 also did a caseecontrol-type study looking at differences in petrous carotid canals in moyamoya. They noted a significantly smaller CCD in patients with moyamoya compared with control patients. They studied 35 patients who were ageand sex-matched. Their population included both pediatric and adult patients. We age-, sex-, and race-matched our patient population and only studied adults, but still found a significant narrowing of the petrous carotid canal in our moyamoya population compared with controls.16 Pediatric studies have additionally noted that agenesis of the carotid canal is seen in agenesis of the ICA.17 Yet other studies suggest that the process begins with the arteries themselves rather than cephalometrics. Some suggest that diminished shear stress in the ICA region can predispose to development of moyamoya.18 Another study
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showed that vessels affected by moyamoya show concentric enhancement, whereas those from intracranial atherosclerosis show eccentric enhancement, suggesting a different pathophysiological process originating in the arteries themselves.19 Kim et al.20 suggest that flow changes in the ICA throughout the petrous canal results in the intracranial findings of moyamoya disease. They note that patients with moyamoya have shorter distances between the carotid canal to the siphon, significantly lower tortuosity, and less blood flow, despite similar flow velocities. Contrary to Seol et al.,18 by Kim’s analysis the shear stress in the walls of the ICA in patients with moyamoya is actually increased.20 In our case, we noted a significant difference in CCD between our moyamoya and control populations. Interestingly, the difference noted in our study was statistically significant for both right and left sides, regardless of whether the patient had unilateral or bilateral disease, and in the cases of unilateral disease whether it was ipsilateral or contralateral (Table 3). Although this validates the association, it does not provide insight as to causation. FOD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls noted a significantly increased FOD in their moyamoya population compared with controls.21 In our adult cohort of 45 patients with moyamoya, we found no significant difference in FOD with matched controls. BPD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls noted a significantly larger BPD in their moyamoya population compared with controls. In our adult cohort of 45 patients with moyamoya, we found no significant difference in BPD with matched controls.21 Cephalic Index One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls measured cephalic index. The authors noted no significant difference in cephalic index in their moyamoya population compared with controls.21 In our adult cohort of 45 patients with moyamoya, we also found no significant difference in cephalic index with matched controls. BOD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls. The authors noted a significantly decreased BOD in their moyamoya population compared with controls.21 In our adult cohort of 45 patients
REFERENCES 1. Takeuchi K, Shimizu K. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve. 1957;9: 37-43.
2. Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20:288-299.
with moyamoya, we found no significant difference in BOD with matched controls. A possible explanation for this discrepancy may be the image used to measure BOD, with Qureshi et al.21 using the sagittal scout CT head image and our study using sagittal views of CTA head. Use of the CTA instead of plain CT allowed us to track the coronal suture until reaching the bregma, which would not be possible on a single scout image. Further Discussion Our series validates the previously reported association with smaller petrous CCD in moyamoya. To our knowledge, our series is the largest to date, including 45 patients, and includes only adult patients, whereas Watanabe et al.15 and Motoshima et al.16 studied all ages, including pediatric patients. Although our validation of this association does not offer insight as to which occurs first, carotid canal narrowing or progressive ICA occlusion, or whether neither of the 2 are causative, but simply both downstream manifestations of another disease process, there remains a definite statistical difference in CCD between patients with moyamoya and matched controls. Interestingly, the difference noted in our study was statistically significant for both right and left sides, regardless of whether the patient had unilateral or bilateral disease, and in the cases of unilateral disease whether it was ipsilateral or contralateral. Furthermore, to our knowledge, our study offers the largest overview of matched patients with moyamoya to assess for FOD, BPD, BOD, and cephalic index. When compared with age-, sex-, and racematched controls, we found no significant difference. There are 2 notable epidemiologic differences to note between our case and control populations. There were 4 patients with sickle cell disease in the moyamoya group with none in the control group. Sickle cell disease is a known risk factor for development of moyamoya. There was anticoagulant use present in 5 patients in the control group with none in the moyamoya group. Considering that our control patients were selected from patients with ischemic stroke rather than hemorrhagic stroke, and we focused mostly on cephalometrics rather than volume or distribution of ischemia, this difference is unlikely to affect our data in a meaningful way. CONCLUSIONS There are no significant differences in FOD, BPD, BOD, and cephalic index in adult patients with moyamoya disease compared with matched controls. CCD is significantly smaller bilaterally in adult patients with moyamoya disease compared with matched controls. Further studies are needed to determine the clinical relevance of this association.
3. Oka K, Yamashita M, Sadoshima S, Tanaka K. Cerebral haemorrhage in Moyamoya disease at autopsy. Virchows Arch A Pathol Anat Histol. 1981;392: 247-261.
4. Iwama T, Morimoto M, Hashimoto N, Goto Y, Todaka T, Sawada M. Mechanism of intracranial rebleeding in moyamoya disease. Clin Neurol Neurosurg. 1997;99(suppl 2):S187-S190.
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5. Wakai K, Tamakoshi A, Ikezaki K, et al. Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey. Clin Neurol Neurosurg. 1997;99(suppl 2):S1-S5. 6. Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology. 2005;65:956-958. 7. Hwang SW, Jea A. A review of the neurological and neurosurgical implications of Down
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syndrome in children. Clin Pediatr (Phila). 2013;52: 845-856. 8. Kainth DS, Chaudhry SA, Kainth HS, Suri FK, Qureshi AI. Prevalence and characteristics of concurrent down syndrome in patients with moyamoya disease. Neurosurgery. 2013;72:210-215 [discussion: 215]. 9. Suri S, Tompson BD, Cornfoot L. Cranial base, maxillary and mandibular morphology in Down syndrome. Angle Orthod. 2010;80:861-869. 10. Quintanilla JS, Biedma BM, Rodriguez MQ, Mora MT, Cunqueiro MM, Pazos MA. Cephalometrics in children with Down’s syndrome. Pediatr Radiol. 2002;32:635-643.
CEPHALOMETRICS IN PATIENTS WITH MOYAMOYA
14. Graham JM Jr, Kreutzman J, Earl D, Halberg A, Samayoa C, Guo X. Deformational brachycephaly in supine-sleeping infants. J Pediatr. 2005;146: 253-257. 15. Watanabe A, Omata T, Koizumi H, Nakano S, Takeuchi N, Kinouchi H. Bony carotid canal hypoplasia in patients with moyamoya disease. J Neurosurg Pediatr. 2010;5:591-594. 16. Motoshima S, Noguchi T, Kawashima M, et al. Narrowed petrous carotid canal detection for the early diagnosis of moyamoya disease. Fukuoka Igaku Zasshi. 2012;103:206-214. 17. Li S, Hooda K, Gupta N, Kumar Y. Internal carotid artery agenesis: a case report and review of literature. Neuroradiol J. 2017;30:186-191. 18. Seol HJ, Shin DC, Kim YS, et al. Computational analysis of hemodynamics using a twodimensional model in moyamoya disease. J Neurosurg Pediatr. 2010;5:297-301.
12. Kasai K, Richards LC, Brown T. Comparative study of craniofacial morphology in Japanese and Australian aboriginal populations. Hum Biol. 1993; 65:821-834.
19. Ryoo S, Cha J, Kim SJ, et al. High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke. 2014;45:2457-2460.
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Conflict of interest statement: Dr. Gattozzi is a recipient of an NREF (Neurosurgery Research and Education Foundation) grant to study adult stem cell transplantation in a rodent model of cerebral ischemia. Dr. Gronseth is an editor for the journal Neurology and is the methodologist for the AAN (American Academy of Neurology). Portions of this work were presented in poster form at the University of Kansas Resident and Fellow Research Forum in Kansas City, Kansas, USA in May 2018. Received 15 April 2019; accepted 29 June 2019
11. Ball R, Shu C, Xi P, Rioux M, Luximon Y, Molenbroek J. A comparison between Chinese and Caucasian head shapes. Appl Ergon. 2010;41: 832-839.
13. Moate SJ, Darendeliler MA. Cephalometric norms for the Chinese: a compilation of existing data. Aust Orthod J. 2002;18:19-26.
21. Qureshi AI, Gilani WI, Gilani SI, Adil MM. Cephalometric features of moyamoya disease: a case control study. J Vasc Interv Neurol. 2014;7:13-18.
20. Kim T, Bang JS, Kwon OK, et al. Morphology and related hemodynamics of the internal carotid arteries of moyamoya patients. Acta Neurochir (Wien). 2015;157:755-761.
Citation: World Neurosurg. (2019) 130:e831-e838. https://doi.org/10.1016/j.wneu.2019.06.233 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.233
Case-Control Study of Cephalometrics in Patients with Moyamoya Nida Faheem1, Domenico A. Gattozzi2, Ernest J. Madarang3, Paul J. Camarata2, Gary S. Gronseth1
OBJECTIVE: To determine whether cranial metrics consistently differed between patients with moyamoya and age-, sex-, and race-matched controls.
-
METHODS: Patients diagnosed with moyamoya disease by cerebral angiogram were obtained from a prospectively collected database through the Department of Neurosurgery at the University of Kansas Medical Center. Control patients matched by decade of age, sex, and race were collected through a deidentified hospital database by International Classification of Diseases-9 and 10 codes for ischemic stroke to identify patients with computed tomography angiograms. Imaging studies for both groups were analyzed to obtain 6 skull metrics: maximum anterior to posterior distance, maximum biparietal distance, bregma to occiput distance, right carotid canal diameter (CCD), left CCD, and cephalic index.
-
RESULTS: Forty-five patients were identified in each cohort. Measurements of mean anterior to posterior skull diameter, mean biparietal skull diameter, bregma to occiput distances, and calculated cephalic index did not demonstrate a statistically significant difference between patients with moyamoya and control patients. Right carotid canal mean diameter was 4.8 mm for the moyamoya group and 5.4 mm for the control group, with a significant raw mean difference of L0.61 mm (95% confidence interval, L0.95 to L0.27). Left CCD was 4.7 mm for the moyamoya group and 5.5 mm for the control group, resulting in a significant raw mean difference of L0.76 mm (95% confidence interval, L1.09 to L0.43).
-
Key words Carotid canal - Cephalometric - Ischemic stroke - Moyamoya - Skull -
Abbreviations and Acronyms BOD: Bregma to occiput distance BPD: Biparietal diameter CCD: Carotid canal diameter CI: Confidence interval CT: Computed tomography CTA: Computed tomography angiogram FOD: Fronto-occipital diameter
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CONCLUSIONS: This study identified 2 skull parameters as statistically different in patients with moyamoya compared with a matched control group of patients with ischemic stroke: right CCD and left CCD.
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INTRODUCTION
A
lthough Takeuchi and Shimizu1 first described a patient with bilateral hypoplasia of the internal carotid arteries in 1957, the term “moyamoya disease,” meaning a “vague or hazy puff of smoke” in Japanese, was not used until 1969, when Suzuki and Takaku2 identified a characteristic angiographic appearance of dilated, skull-base collateral arteries that form in response to brain ischemia. Moyamoya disease typically causes progressive, bilateral supraclinoid internal carotid artery (ICA) stenosis that can also involve proximal portions of the middle cerebral and/or anterior cerebral arteries. The posterior circulation is rarely involved, even in advanced cases. Small collateral vessels form from the Circle of Willis, intracranial portion of the ICA, anterior choroidal artery, and posterior cerebral arteries to communicate with the lenticulostriate or thalamoperforating arteries. This aids reconstitution of blood flow distal to the site of vessel occlusion.3 Clinically, patients experience both ischemic infarcts secondary to progressive anterior circulation stenosis and hemorrhagic infarcts related to fragility of the small, thin-walled collateral vessels.4 Although moyamoya has been identified in patients worldwide, there is a predominance of the disease in East Asian populations—specifically Japan, China, and Korea. Surveys in Japan in
HERON: Healthcare Enterprise Repository for Ontological Narration ICA: Internal carotid artery RMD: Raw mean difference From the Departments of 1Neurology, 2Neurosurgery, and 3Radiology, University of Kansas Medical Center, Kansas City, Kansas, USA To whom correspondence should be addressed: Domenico A. Gattozzi, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019) 130:e831-e838. https://doi.org/10.1016/j.wneu.2019.06.233 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
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Figure 1. Examples of the cephalometrics assessed. (A) Maximum anterior to posterior diameter, (B) biparietal diameter, (C) bregma to occiput
2006, estimated an annual incidence of 0.94 patients per 100,000 population per year.5 In comparison, hospital discharge data in 2005, from the western United States reported a significantly lower incidence of 0.086 per 100,000 population per year. There is also a 2-to-1 female-to-male ratio.6 Several conditions have been strongly associated with moyamoya disease including radiotherapy of the head or neck, neurofibromatosis type 1, sickle cell anemia, and Down syndrome. Down syndrome has a 26-fold greater prevalence in patients with coexisting moyamoya disease (3760 per 100,000) compared with the prevalence of Down syndrome among live births (145 per 100,000).7,8 The question arises then if there is a shared characteristic between Down Syndrome and an East Asian racial background underlying the association with moyamoya disease. Cephalometric analyses of patients with Down syndrome have demonstrated brachycephaly with reduced anterior and posterior
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diameter, (D) carotid canal diameter (CCD), green square delineating close-up area for (E) CCD close-up.
cranial base lengths.9 This likely occurs secondary to craniosynostosis, specifically with premature ossification of the coronal suture. Restriction of the skull’s growth in the anterior and posterior directions results in brachycephaly with recessed frontal bones and a flattened occiput.10 Similarly, cephalometric analyses of East Asian and Caucasian skulls demonstrate brachycephaly with a flatter back and forehead in East Asian patients.11-13 Other observational studies have additionally noted non-craniosynostosis deformational brachycephaly in infants of predominantly supine-sleeping cultures such as Japan and Korea, as opposed to prone-sleeping Western cultures.14 We sought to delineate a consistent correlation between skull metrics and moyamoya disease, with a hypothesis that patients with moyamoya had a shorter anterior to posterior cranial diameter and decreased bregma to occiput distance (BOD) (indicative of a flatter occiput) compared with non-moyamoya
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Table 1. Continued
Table 1. Background Characteristics Moyamoya
Control
Sex Male
11
11
Female
34
34
Moyamoya
Control
60e70
0
0
80e90
0
0
4
4
Male
3
3
Female
1
1
Asian Sex
Age (years) (% male) 16e19
2 (0%)
2 (0%)
20e30
22 (23%)
22 (23%)
Age (years) (% male)
40e50
16 (25%)
16 (25%)
60e70
5 (40%)
5 (40%)
16e19
0
0
0
20e30
0
0
40e50
3 (66%)
3 (66%)
60e70
1 (100%)
1 (100%)
80e90
0
0
4
4
Male
1
1
Female
3
3
80e90
0
Race White
24
24
Sex Male Female
3 21
3
Other
21
Sex
Age (years) (% male) 16e19
1 (0%)
1 (0%)
Age (years) (% male)
20e30
12 (17%)
12 (17%)
40e50
9 (11%)
9 (11%)
16e19
1 (0%)
1 (0%)
60e70
2 (0%)
2 (0%)
20e30
1 (0%)
1 (0%)
0
0
40e50
1 (0%)
1 (0%)
11
11
60e70
1 (100%)
1 (100%)
80e90
0
0
9 (20%)
8 (18%)
80e90 Black Sex Male
4
4
Diabetes
Female
7
7
Hypertension
24 (53%)
25 (56%)
Tobacco use
18 (40%)
21 (47%)
Coagulopathy
1 (2%)
2 (4%)
4 (9%)
0
38 (84%)
45 (100%)
Age (years) (% male) 16e19
0
0
20e30
7 (43%)
7 (43%)
Sickle cell disease
40e50
3 (33%)
3 (33%)
Ischemic stroke
60e70
2 (50%)
2 (50%)
Hemorrhagic stroke
8 (18%)
3 (7%)
28 (62%)
25 (56%)
0
5 (11%)
0
0
Antiplatelet use
2
2
Anticoagulation use
Male
0
0
Female
2
2
80e90 Hispanic Sex
Age (years) (% male) 16e19
0
0
20e30
2 (0%)
2 (0%)
40e50
0
0 Continues
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controls. If a statistically significantly different metric was noted, we planned to incorporate this into a scoring system for earlier identification of progressive moyamoya disease. METHODS Study Design Approval for this study was received by an institutional review board committee for ethical standards on human
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Table 2. Results Moyamoya
Controls
Measure
Mean
SD
Number
Mean
SD
Number
APD
160.143
9.004
45
161.496
9.089
45
BPD
134.039
7.244
45
132.940
7.944
45
BOD
140.098
6.076
45
141.432
4.645
45
RCC
4.802
0.861
45
5.410
0.765
45
0.764
1.093
LCC
4.693
0.899
45
5.457
0.678
45
CI%
83.887
5.521
45
82.400
5.084
45
RMD
LCL
UCL
5.092
2.384
2.042
4.240
1.334
3.568
0.901
0.608
0.944
1.354 1.099
1.487
0.706
0.271 0.435 3.680
APD, anterior-posterior diameter; BOD, bregma to occiput distance; BPD, biparietal diameter; CI, confidence interval; LCC, left carotid canal diameter; LCL, lower confidence level; RCC; right carotid canal diameter; RMD, raw mean difference; SD, standard deviation; UCL, upper confidence level.
experimentation. This study was a caseecontrol design. Patients with moyamoya were identified through a previously collected neurosurgery database at the University of Kansas Medical Center. Control patients were selected through the HERON (Healthcare Enterprise Repository for Ontological Narration) deidentified patient database with International Classification of Diseases-9 and 10 codes for ischemic stroke. Patients with ischemic stroke were
Figure 2. Scatter plot comparing cephalometric measurements between moyamoya and control populations. FOD Diam, fronto-occipital diameter;
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chosen because of the availability of computed tomography angiograms (CTAs) necessary for all skull metrics. Inclusion criteria for patients with moyamoya were as follows: patients were between the ages of 16 and 90 years, diagnosed with moyamoya disease (no distinction was made for primary or secondary moyamoya disease) by cerebral angiogram, with at least 1 CTA for the purposes of measuring cranial metrics, and at least 2 cerebral
BP Diam, biparietal diameter; BOD, bregma to occiput distance.
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Figure 3. Scatter plot comparing left and right carotid canal diameters (CCDs) between moyamoya and control populations. LCC Diam, left CCD; RCC Diam, right CCD.
angiograms to be reviewed in the second part of this study for Suzuki staging. Control patients were included if between the ages of 16 and 90 years, diagnosed with an ischemic stroke, and had at least 1 CTA for the purposes of measuring cranial metrics. Pediatric patients, patients with Down Syndrome, and those with traumatic, surgical, or other significant cranial deformity were excluded from both groups. Patients with moyamoya were sorted by sex, then decade of age (16e19, 20e30, 40e50, 60e70, and 80e90 years), and race (white, black, Hispanic, Asian, or other—with other defined as distinct from the 4 prior racial backgrounds, a mixed racial background, or unidentified). These were then matched based on sex, decade of age, and race to non-moyamoya control patients. Basic vascular risk factors including diabetes, hypertension, tobacco use, coagulopathies, ischemic stroke, hemorrhagic stroke, and sickle cell disease were assessed. Antithrombotic use at time of presentation (antiplatelet or anticoagulant use) was additionally recorded. Under instructions of a neuroradiologist, primary investigators obtained 4 cranial measurements on each patient in the moyamoya and control groups: maximum anterior to posterior diameter from inner bony mantle at the level of the nasion to inner bony mantle at the level of the inion, maximum biparietal diameter (BPD) measured from outer bony mantle bilaterally, maximum distance from bregma (visualized on sagittal CTA head as converging point of coronal and sagittal sutures) to posterior aspect of the foramen magnum at the base of the occiput, and maximum width of the carotid canal bilaterally was measured at mid-way through the transverse portion of each canal in the petrous bone (Figure 1). The measurements obtained on axial sequences (fronto-occipital diameter [FOD], BPD, carotid canal diameter [CCD]) were obtained on thin-cut computed tomography (CT) sequences with a slice thickness of 0.625 mm, with approximately 256 images in the series. The measurements obtained on sagittal sequences (BOD) were obtained on sagittal
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reconstruction of the axial images, with approximately 91 images in the series. Cephalic indices were also calculated by dividing BPD by FOD and multiplying by 100. Patients with agenesis of the carotid canal were excluded; all patients included had a measurable CCD on imaging. Average measure and standard deviation for each parameter was obtained per group. Analysis of variance was performed and the raw mean difference (RMD) of the variance, along with 95% confidence intervals (CIs), was calculated for each parameter per group. RESULTS Forty-five patients were identified in each cohort. Table 1 demonstrates background characteristics of the moyamoya and control patients. Overall, there was a greater predominance of women compared with men, with 34 women and 11 men in both moyamoya and control groups. Patients were primarily in the age group 20e30 (22 patients, 23%) years, or 40e50 (16 patients, 25%) years. Average age of the moyamoya group at presentation to the neurosurgery service was 39 years; average age of the control group was 41 years. Assessed by racial background, white patients comprised most of the moyamoya and matched controls (24 patients), followed by black (11 patients), Asian (4 patients), Hispanic (2 patients), and other (4 patients). Moyamoya and matched controls were fairly similar across the vascular risk factors, with notable differences being 4 patients with sickle cell disease in the moyamoya group—a known associated risk factor—and anticoagulant use in 5 patients in the ischemic stroke control group, whereas zero patients were on anticoagulants in the moyamoya cohort (Table 1). Mean anterior to posterior diameter for patients with moyamoya was 160.1 mm compared with 161.5 mm for the controls, with a non-significant RMD of 1.4 mm (95% CI, 5.01 to 2.38). Mean
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Table 3. Carotid Canal Diameters Associated with Moyamoya Disease Laterality
Table 3. Continued Left CCD
Affected Side
6.4
6.5
Right
6
6.1
Right
Both
4.31
4.27
Right
4.7
Both
4.5
4.3
Right
4.4
5.7
Both
3.6
3.3
Right
5.6
4.8
Both
5.1
5.3
Right
5.2
5.76
Both
3.22
5.6
Right
5.5
4.96
Both
CCD, carotid canal diameters.
4.9
4.77
Both
4.57
4.48
Both
4.14
4.37
Both
4.36
4.45
Both
2.84
2.89
Both
2.3
3.65
Both
6.19
4.77
Both
5.13
4.91
Both
4.17
4.5
Both
4.3
4.27
Both
3.5
2.95
Both
4.37
4.95
Both
4.1
4.1
Both
4.64
5.2
Both
5.62
5.7
Both
4.5
4.7
Both
5.6
5.8
Both
4.79
5.3
Both
5.8
6.3
Both
4.63
3.3
Both
4.49
4.5
Both
4.48
4.7
Both
6.02
5.4
Both
5.31
6.1
Both
5.2
5.3
Both
4.78
4.73
Left
5.85
4.62
Left
3.9
4.2
Left
3.18
3.9
Left
5.21
5.8
Left
4.8
4.8
Right
Right CCD
Left CCD
Affected Side
4.1
4.1
Both
4.2
5.5
5.2
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Right CCD
BPD for patients with moyamoya was 134.0 mm compared with 132.9 mm for the controls, with a non-significant RMD of 1.1 mm (95% CI, 2.04 to 4.24). BODs were 140.1 mm for the moyamoya group and 141.4 mm for the control group; this resulted in a nonsignificant RMD of 1.33 mm (95% CI, 3.6 to 0.90). Right carotid canal mean diameter was 4.8 mm for the moyamoya group and 5.4 mm for the control group, with a significant RMD of 0.61 mm (95% CI, 0.95 to 0.27). Left CCD was 4.7 mm for the moyamoya group and 5.5 mm for the control group, resulting in a significant RMD of 0.76 mm (95% CI, 1.09 to 0.43). Cephalic index (BPD divided by anterior to posterior distance, multiplied by 100) was 83.8% for the moyamoya group, 82.4% for the control group; this yielded a non-significant RMD of 1.5% (Table 2; Figures 2 and 3). DISCUSSION CCD Watanabe et al.15 studied the CT scans of 60 adult patients without moyamoya who obtained CT scans for other reasons (headache, trauma, etc.). They found that of the 60 unaffected non-matched adults, the bony carotid canal was on average 5.27 mm wide, whereas in their 11 reported adult patients with moyamoya it was on average 3.31 mm. In addition, they studied the CT scans of 50 pediatric patients, 10 of which were aged <2 years to trend growth and development.15 Motoshima et al.16 also did a caseecontrol-type study looking at differences in petrous carotid canals in moyamoya. They noted a significantly smaller CCD in patients with moyamoya compared with control patients. They studied 35 patients who were ageand sex-matched. Their population included both pediatric and adult patients. We age-, sex-, and race-matched our patient population and only studied adults, but still found a significant narrowing of the petrous carotid canal in our moyamoya population compared with controls.16 Pediatric studies have additionally noted that agenesis of the carotid canal is seen in agenesis of the ICA.17 Yet other studies suggest that the process begins with the arteries themselves rather than cephalometrics. Some suggest that diminished shear stress in the ICA region can predispose to development of moyamoya.18 Another study
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showed that vessels affected by moyamoya show concentric enhancement, whereas those from intracranial atherosclerosis show eccentric enhancement, suggesting a different pathophysiological process originating in the arteries themselves.19 Kim et al.20 suggest that flow changes in the ICA throughout the petrous canal results in the intracranial findings of moyamoya disease. They note that patients with moyamoya have shorter distances between the carotid canal to the siphon, significantly lower tortuosity, and less blood flow, despite similar flow velocities. Contrary to Seol et al.,18 by Kim’s analysis the shear stress in the walls of the ICA in patients with moyamoya is actually increased.20 In our case, we noted a significant difference in CCD between our moyamoya and control populations. Interestingly, the difference noted in our study was statistically significant for both right and left sides, regardless of whether the patient had unilateral or bilateral disease, and in the cases of unilateral disease whether it was ipsilateral or contralateral (Table 3). Although this validates the association, it does not provide insight as to causation. FOD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls noted a significantly increased FOD in their moyamoya population compared with controls.21 In our adult cohort of 45 patients with moyamoya, we found no significant difference in FOD with matched controls. BPD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls noted a significantly larger BPD in their moyamoya population compared with controls. In our adult cohort of 45 patients with moyamoya, we found no significant difference in BPD with matched controls.21 Cephalic Index One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls measured cephalic index. The authors noted no significant difference in cephalic index in their moyamoya population compared with controls.21 In our adult cohort of 45 patients with moyamoya, we also found no significant difference in cephalic index with matched controls. BOD One study on a population of 13 patients with moyamoya compared with age-, sex-, and race-matched controls. The authors noted a significantly decreased BOD in their moyamoya population compared with controls.21 In our adult cohort of 45 patients
REFERENCES 1. Takeuchi K, Shimizu K. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve. 1957;9: 37-43.
2. Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20:288-299.
with moyamoya, we found no significant difference in BOD with matched controls. A possible explanation for this discrepancy may be the image used to measure BOD, with Qureshi et al.21 using the sagittal scout CT head image and our study using sagittal views of CTA head. Use of the CTA instead of plain CT allowed us to track the coronal suture until reaching the bregma, which would not be possible on a single scout image. Further Discussion Our series validates the previously reported association with smaller petrous CCD in moyamoya. To our knowledge, our series is the largest to date, including 45 patients, and includes only adult patients, whereas Watanabe et al.15 and Motoshima et al.16 studied all ages, including pediatric patients. Although our validation of this association does not offer insight as to which occurs first, carotid canal narrowing or progressive ICA occlusion, or whether neither of the 2 are causative, but simply both downstream manifestations of another disease process, there remains a definite statistical difference in CCD between patients with moyamoya and matched controls. Interestingly, the difference noted in our study was statistically significant for both right and left sides, regardless of whether the patient had unilateral or bilateral disease, and in the cases of unilateral disease whether it was ipsilateral or contralateral. Furthermore, to our knowledge, our study offers the largest overview of matched patients with moyamoya to assess for FOD, BPD, BOD, and cephalic index. When compared with age-, sex-, and racematched controls, we found no significant difference. There are 2 notable epidemiologic differences to note between our case and control populations. There were 4 patients with sickle cell disease in the moyamoya group with none in the control group. Sickle cell disease is a known risk factor for development of moyamoya. There was anticoagulant use present in 5 patients in the control group with none in the moyamoya group. Considering that our control patients were selected from patients with ischemic stroke rather than hemorrhagic stroke, and we focused mostly on cephalometrics rather than volume or distribution of ischemia, this difference is unlikely to affect our data in a meaningful way. CONCLUSIONS There are no significant differences in FOD, BPD, BOD, and cephalic index in adult patients with moyamoya disease compared with matched controls. CCD is significantly smaller bilaterally in adult patients with moyamoya disease compared with matched controls. Further studies are needed to determine the clinical relevance of this association.
3. Oka K, Yamashita M, Sadoshima S, Tanaka K. Cerebral haemorrhage in Moyamoya disease at autopsy. Virchows Arch A Pathol Anat Histol. 1981;392: 247-261.
4. Iwama T, Morimoto M, Hashimoto N, Goto Y, Todaka T, Sawada M. Mechanism of intracranial rebleeding in moyamoya disease. Clin Neurol Neurosurg. 1997;99(suppl 2):S187-S190.
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5. Wakai K, Tamakoshi A, Ikezaki K, et al. Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey. Clin Neurol Neurosurg. 1997;99(suppl 2):S1-S5. 6. Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology. 2005;65:956-958. 7. Hwang SW, Jea A. A review of the neurological and neurosurgical implications of Down
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syndrome in children. Clin Pediatr (Phila). 2013;52: 845-856. 8. Kainth DS, Chaudhry SA, Kainth HS, Suri FK, Qureshi AI. Prevalence and characteristics of concurrent down syndrome in patients with moyamoya disease. Neurosurgery. 2013;72:210-215 [discussion: 215]. 9. Suri S, Tompson BD, Cornfoot L. Cranial base, maxillary and mandibular morphology in Down syndrome. Angle Orthod. 2010;80:861-869. 10. Quintanilla JS, Biedma BM, Rodriguez MQ, Mora MT, Cunqueiro MM, Pazos MA. Cephalometrics in children with Down’s syndrome. Pediatr Radiol. 2002;32:635-643.
CEPHALOMETRICS IN PATIENTS WITH MOYAMOYA
14. Graham JM Jr, Kreutzman J, Earl D, Halberg A, Samayoa C, Guo X. Deformational brachycephaly in supine-sleeping infants. J Pediatr. 2005;146: 253-257. 15. Watanabe A, Omata T, Koizumi H, Nakano S, Takeuchi N, Kinouchi H. Bony carotid canal hypoplasia in patients with moyamoya disease. J Neurosurg Pediatr. 2010;5:591-594. 16. Motoshima S, Noguchi T, Kawashima M, et al. Narrowed petrous carotid canal detection for the early diagnosis of moyamoya disease. Fukuoka Igaku Zasshi. 2012;103:206-214. 17. Li S, Hooda K, Gupta N, Kumar Y. Internal carotid artery agenesis: a case report and review of literature. Neuroradiol J. 2017;30:186-191. 18. Seol HJ, Shin DC, Kim YS, et al. Computational analysis of hemodynamics using a twodimensional model in moyamoya disease. J Neurosurg Pediatr. 2010;5:297-301.
12. Kasai K, Richards LC, Brown T. Comparative study of craniofacial morphology in Japanese and Australian aboriginal populations. Hum Biol. 1993; 65:821-834.
19. Ryoo S, Cha J, Kim SJ, et al. High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke. 2014;45:2457-2460.
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Conflict of interest statement: Dr. Gattozzi is a recipient of an NREF (Neurosurgery Research and Education Foundation) grant to study adult stem cell transplantation in a rodent model of cerebral ischemia. Dr. Gronseth is an editor for the journal Neurology and is the methodologist for the AAN (American Academy of Neurology). Portions of this work were presented in poster form at the University of Kansas Resident and Fellow Research Forum in Kansas City, Kansas, USA in May 2018. Received 15 April 2019; accepted 29 June 2019
11. Ball R, Shu C, Xi P, Rioux M, Luximon Y, Molenbroek J. A comparison between Chinese and Caucasian head shapes. Appl Ergon. 2010;41: 832-839.
13. Moate SJ, Darendeliler MA. Cephalometric norms for the Chinese: a compilation of existing data. Aust Orthod J. 2002;18:19-26.
21. Qureshi AI, Gilani WI, Gilani SI, Adil MM. Cephalometric features of moyamoya disease: a case control study. J Vasc Interv Neurol. 2014;7:13-18.
20. Kim T, Bang JS, Kwon OK, et al. Morphology and related hemodynamics of the internal carotid arteries of moyamoya patients. Acta Neurochir (Wien). 2015;157:755-761.
Citation: World Neurosurg. (2019) 130:e831-e838. https://doi.org/10.1016/j.wneu.2019.06.233 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.233