Morphometric analysis of posterior fossa and craniovertebral junction in subtypes of Chiari malformation

Clinical Neurology and Neurosurgery 169 (2018) 1–11

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Morphometric analysis of posterior fossa and craniovertebral junction in subtypes of Chiari malformation

T

⁎

Recep Basarana, , Mustafa Efendioglua, Mehmet Senolb, Selcuk Ozdoganc, Nejat Isika a

Medeniyet University Goztepe Education and Research Hospital, Department of Neurosurgery, Istanbul, Turkey Erzurum Bolge Education and Research Hospital, Department of Neurosurgery, Erzurum, Turkey c Kartal Dr Lutfi Kirdar Education and Research Hospital, Department of Neurosurgery, Istanbul, Turkey b

A R T I C LE I N FO

A B S T R A C T

Keywords: Morphometry Posterior fossa Craniovertebral junction Chiari malformation Anatomy

Objectives: Chiari malformations (CMs) are a group of disorders defined by anatomic anomalies of the cerebellum, brainstem, and craniovertebral junction (CVJ). In this study, we aimed to investigate morphometry of posterior fossa and CVJ in subtypes of CM and in control group, and to bring up a matter a correlation with demographic data and subtypes of CM. Patients and Methods: The study group included patients managed for CM between 2012 and 2016 and control group. Radiological evaluation was studied by special programs and formulas. Intracranial volumes and morphometric datas of posterior fossa and CVJ were recorded retrospectively. Results: Of the 141 patients, 91 had CM and 50 were control group participants. Mean age was 34.75. Patients were classified as CM-0 (n:10), CM-1 (n:45), CM-1.5 (n:21), CM-2 (n:15). There were statistically significance between Chiari subtypes by syringomyelia (SM) presence (p ˂ 0.01), SM localization (p ˂ 0.01), posterior fossa volume (PFV) (p ˂ 0.01), length of clivus (LoC) and length of subocciput (LoSO) (p ˂ 0.01 for both), angle between clivus and subocciput (C-SO angle) (p ˂ 0.01), and clivo-dental angle (C–D angle) (p ˂ 0.01). Conclusion: On morphometric comparison of CM subtypes we concluded that etiological differences lead to morphological differences. CM-2 has remarkable differences from both other subtypes and the control group.

1. Introduction Chiari malformations (CMs) are a group of disorders defined by anatomic anomalies of the cerebellum, brainstem, and craniovertebral junction (CVJ), characterized by downward displacement of the cerebellum into the spinal canal, either alone or together with the lower medulla [1]. There is no certain definition for amount of cerebellar descent. CMs were first described in 1883 by John Cleland [2,3]. In 1891, Hans Chiari classified CMs into four groups [4]; today, they are divided into six groups as Chiari 0, 1, 1.5, 2, 3, and 4 [4–7]. Beyond the earlier classification, Chiari 0 malformation (CM-0) was described as syringomyelia (SM) despite the lack of cerebellar tonsil herniation [8], and Chiari 1.5 malformation (CM-1.5) as a tonsillar herniation within a Chiari I malformation (CM-1), with additional caudal descent of the brainstem through the foramen magnum [5,7]. It is thought that Chiari 1 malformation disorders arise from para-axial mesoderm [9]. Although, Chiari 2, 3 and 4 arise from neuroectoderm [10]. The components of the posterior fossa outgrow the underdeveloped compartment and cause herniation of the tonsils into the upper cervical spinal canal [11]. A number of studies have attributed this insufficient posterior ⁎

cranial fossa geometry to embryological defects in the paraxial mesoderm [12–14]. For accurate diagnosis and treatment of various diseases, it is important for clinicians to know the normal anatomy of the cranial base, especially the foramen magnum and associated structures [15]. As the cranial base can remain intact in cases where the rest of the cranium has been compromised, researchers have analyzed dimorphic traits of this anatomic region for the purposes of gender identification [16,17]. In this study, our objectives are 1) to establish whether intracranial volumes differ in individuals with various subtypes of CMs as compared to healthy individuals; 2) to investigate the correlation within intracranial volumes and CVJ morphometries; 3) to investigate the correlation between syringomyelia and posterior fossa morphometry; 4) to investigate the correlation between CM etiology and posterior fossa morphometry.

Corresponding author at: Medeniyet University Goztepe Education and Research Hospital, Department of Neurosurgery, Doktor Erkin Caddesi, 34722, Kadıkoy, Istanbul, Turkey. E-mail addresses: [email protected], [email protected], [email protected] (R. Basaran).

https://doi.org/10.1016/j.clineuro.2018.03.017 Received 20 January 2018; Received in revised form 12 March 2018; Accepted 19 March 2018 Available online 20 March 2018 0303-8467/ © 2018 Elsevier B.V. All rights reserved.

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Fig. 1. Spheroidal PFV was calculated using the simple spheroidal formula.

2. Material and methods

used to evaluate CMs. All patients underwent magnetic resonance imaging (MRI) (Signa 1.5-Tesla; General Electric), using T2-weighted MRI sequence for all measurements. Linear dimensions were derived using ExtremePacs Workstation 1.5 software (Extreme PACS Healthcare, Ankara, Turkey). To determine a plane parallel to the foramen magnum (FM), MRI of the CVJ was performed at 5 mm intervals parallel to the orbitomeatalline. Measurement of cerebellar descent (CD) was performed on MRI sequences using the same software. Examination protocol is slices parallel to the line joining the Genu and Splenium of the Corpus Callosum. Standart setting are 4–5 mm of slices, 0.9 mm of resolution, 10–40% of gap and 230–250 mm of FOV.

2.1. Patient population Following a retrospective review of patients evaluated or operated for CM at the hospital between December 2012 and February 2016, 91 patients and 50 control cases were included in the study. The study group included patients with or without all CM symptoms, excluding those for whom the available data were insufficient to evaluate cranial volume and morphology, we excluded patients with intracranial pathology and patients with CM-3 because of the bone defect they have. Control cases included patients admitted to the hospital for headache or for reasons other than intracranial pathology.

2.4. Measurement of volume

2.2. Definition of CM

Spheroidal PFV was calculated using the simple spheroidal formula [18]

Subtypes of CMs are almost completely different diseases with diversified clinical and radiological features. According to the previous classification [1,10],

PFV = 4/3 × Π × (X/2 × Y/2 × Z/2), Where x is the anteroposterior measurement from the posterior clinoid process to the torcula; y is the height of the posterior fossa measured from the basion to the peak of the tentorium cerebelli; and z is the maximum width of the posterior fossa (Fig. 1). In children, ICV was calculated using the Dekaban spheroidal formula, which estimates cranial volume in individuals up to 20 years of age[19–21]:

• Chiari I malformation (CM-I) is characterized by abnormally shaped cerebellar tonsils displaced below the level of the foramen magnum; • Chiari II malformation (CM-II) is characterized by downward dis• •

placement of the cerebellar vermis and tonsils, brainstem malformation with beaked midbrain on neuroimaging, and spinal myelomeningocele; Chiari III malformation (CM-III) is rare and combines a small posterior fossa with a high cervical or occipital encephalocele, usually with displacement of cerebellar structures into the encephalocele, and often with inferior displacement of the brainstem into the spinal canal; Chiari IV malformation (CM-IV) is now considered to be an obsolete term that describes cerebellar hypoplasia unrelated to the other CMs.

Adult male ICV (cm3) = [0.000337 × (length – 11).(breadth –11). (height – 11) + 406.01 cm3;

In addition to the previous classification,

Adult female ICV (cm3) = [0.0004 × (length – 11).(breadth –11). (height – 11) + 206.60 cm3·

ICV (cm3) = 0.523 × (length – 2 t) × (breadth – 2 t) × (height – t), Where t = thickness of skull and scalp. In adult males and females, ICV was calculated using the formula derived by Lee-Pearson [20,21]:

• Chiari 0 malformation is SM despite the lack of cerebellar tonsil herniation [8]; • Chiari 1.5 malformation involves tonsillar herniation within a Chiari

In adults, maximum anteroposterior (AP) length was measured between the glabella and the inion; maximum breadth was measured between the two parietal eminences; and cranial height was measured as basibregmatic height (Fig. 2).

I malformation, with additional caudal descent of the brainstem through the foramen magnum [7].

2.5. Measurement of foramen magnum area 2.3. Radiological evaluation

The area of the foramen magnum (FMA) was calculated using the formula derived by Radinsky [22]:

All radiological values were reported from a single measurement from the same observers (RB). A lateral view radiograph of the CVJ was

FMA = 1/4 × FML × FMW, 2

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Fig. 2. In children (˂20 yrs), ICV was calculated using the Dekaban spheroidal formula, in adult males and females (≥20 yrs), ICV was calculated using the formula derived by LeePearson.

Fig. 3. The area of the foramen magnum (FM) was calculated using the formula derived by Radinsky.

2.9. Angle of the clivus and tentorium

Where (mathematical constant) = 22/7, FML = foramen magnum length and FMW = foramen magnum width (Fig. 3).

2.6. Length of the clivus and supra-occiput

The angle between clivus and tentorium (C–T angle) is important for superior compression to structures of the posterior fossa. It is constructed by drawing a line along the clivus and another along the tentorium (Fig. 7).

The distance from the top of the dorsum sella to the basion was defined as the length of the clivus (LoC), and the length of the subocciput (LoSO) was measured as the distance between the internal occipital protuberance and the opisthion [23](Fig. 4).

2.10. Angle of the clivus and subocciput The angle between clivus and supra-occiput (C-SO angle) is constructed by drawing a line along the clivus and another line along the subocciput (Fig. 8).

2.7. Tentorial slope

2.11. Statistical analysis

Tentorial slope (TS) was obtained by measuring the angle between the tentorium and Twining’s line on a midsagittal head MRI scan (Fig. 5).

Following data collection and tabulation, the data were analyzed using IBM SPSS. Descriptive statistics including range, mean, and standard deviation were calculated for each parameter. Normality was assessed using the Kolmogorov-Smirnov test. For normal distributions, mean differences in dimensions of the posterior fossa, volume of posterior fossa, and measurements of the occipital bone for study and control groups were assessed using independent-sample Student’s ttests and Spearman’s rho. Significance was indicated by a two-tailed test with p value < 0.05 and 95% confidence intervals. For abnormal distributions, one-way ANOVA, Mann Whitney U, and Kruskall Wallis tests were used.

2.8. Clivodental angle The clivodental angle (C–Dangle)is known as Wackenheim’s clivus base line or the craniovertebral angle. It is constructed by drawing a line along the clivus and extrapolating inferiorly into the upper cervical spinal canal along the posterior surface of the odontoid bone (Fig. 6). This line should fall tangential to the posterior aspect of the tip of the odontoid process [24]. 3

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Fig. 4. The distance from the topof the dorsum sella to the basion was defined as the length of the clivus (LoC), and the length of the subocciput (LoSO) was measured as the distance between the internal occipital protuberance and the opisthion.

3. Results

changes due to CM subtypes are shown in Table 2. SM was detected in 42.85% (39/91) of the patient group; of these, 25.64%(10/39) were cervical; 61.53% (24/39) were cervicodorsal; and 12.81% (5/39) were dorsal. The relations between age and ICV (p: 0.032), PFV (p: 0.048), and C-SO angle (p: 0.034) were found to be statistically significant. Statistically significances were also found between the sex for ICV (p ˂ 0.01), PFV (˂0.01), and LoC (p: 0.033) (see Table 1). Additionally, statistically significances were found between patient and control groups for ICV (cm3) (p: 0.037), PFV/ICV (p ˂ 0.01), C–D angle (p ˂ 0.01), and C-SO angle (p ˂ 0.01) (see Table 1). There were statistically significances between Chiari subtypes by age (p: 0.034), SM presence (p ˂ 0.01), SM localization (p ˂ 0.01), PFV

Of the 141 patients included in our study, 91 had CM and 50 were control group participants. 39of the patient group had been operated for CM and/or SM; 52 were followed up without surgery. The patient group ranged in age between 2 and 65 years, with a mean age of 34.75 ± 16.59. The control group was ranged in age between 4 and 67 years, with a mean age of 40.14 ± 16.67. The patient group included 28 males and 63 females, and the control group included 12 males and 38 females. The relationship of age and sex for the two groups is shown in Table 1. Patients with CM were classified as follows:10 cases ofCM-0, 45 cases ofCM-1, 21 cases ofCM-1.5and 15 cases of CM-2.Morphological

Fig. 5. Tentorial slope (TS) was obtained by measuring the angle between the tentorium and Twining’s line on a midsagittal head MRI scan.

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Fig. 6. The clivodental (CD) angle is known as Wackenheim’sclivus base line or the craniovertebral angle. It is constructed by drawing a line along the clivus and extrapolating inferiorly into the upper cervical spinal canal along the posterior surface of the odontoid bone.

(p ˂ 0.01) and C-SO angle. There were also differences of age, PFV, PFV/ICV, TS, C–T angle and C–D angle but these results were not statistically significant (p ˃ 0.05). For CM-1, statistically significant differences were found between Chiari 1 and 1.5 for LoC (p: 0.049), and between Chiari 1 and 2 for SM localization (p: 0.015), PFV (p ˂ 0.01), PFV/ICV (p: 0.047), FMA/PFV (p ˂ 0.01), LoSO (p ˂ 0.01), and LoC (p ˂ 0.01).

(p ˂ 0.01), FMA/PFV (p ˂ 0.01), PFV/ICV (p: 0.040), LoC and LoSO (p ˂ 0.01for both), C-SO angle (p ˂ 0.01), and C–D angle (p ˂ 0.01). Differences were also detected between Chiari subtypes for ICV (p: 0.095), TS (p: 0.068), and FMA/ICV (p: 0.075), but these results were not statistically significant (see Table 3). For CM-0, statistically significant differences were found between Chiari 0 and 2for SM localization (p ˂ 0.01), FMA/PFV (p ˂ 0.01), LoSO

Fig. 7. The angle between clivus and tentorium (C–T angle) is important for superior compression to structures of the posterior fossa. It is constructed by drawing a line along the clivus and another along the tentorium.

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Fig. 8. The angle between clivus and supra-occiput (C-SO angle) is constructed by drawing a line along the clivus and another line along the subocciput.

is an obvious statistical difference between SM presence and TS, it was not found to be statistically significant (p: 0.075). On examining differences between SM localizations, statistically significant differences were found between SM localization and SM width (p ˂ 0.01), PFV (p ˂ 0.01), PFV/ICV (p ˂ 0.01), FMA/PFV (p: 0.014), and cerebellar descent (p: 0.023). Although there is a clear statistical difference between SM localization and age, it was not found to be statistically significant (p: 0.057) (Table 4). Results of the examination of SM localizations and morphological features are shown in Table 4. On examining factors influencing decision to operate, a statistically significant correlation was detected between decision to operate and SM presence (p: 0.002), SM width (p: 0.010), ICV (p: 0.031), FMA (p ˂ 0.01), PFV/ICV (p ˂ 0.01), FMA/PFV (p: 0.026), FMA/ICV (p ˂ 0.01), and C–D angle (p: 0.015). Although there is an obvious statistical difference between decision to operation and PFV, it was not found to be statistically significant (p ˃ 0.05) (Table 4).

For CM-1.5, statistically significant differences were found between Chiari 1.5 and 2 for SM localization (p ˂ 0.01), PFV (p: 0.014), and FMA/PFV (p ˂ 0.01), and between Chiari 1.5 and the control group for C-SO angle (p ˂ 0.01) and C–D angle (p: 0.034). In addition to the above results, statistically significant differences were found between Chiari 2 and control group participants for PFV (p ˂ 0.01), FMA/PFV (p ˂ 0.01), LoC (p ˂ 0.01), LoSO (p ˂ 0.01),and C–D angle (p ˂ 0.01). Statistically significant differences were detected between CD length and FMA (p ˂ 0.01), FMA/PFV ratio (p ˂ 0.01), FMA/ICV ratio (p ˂ 0.01), LoC (p ˂ 0.01), LoSO (p ˂ 0.01), and C–D angle (p: 0.015). The difference between PFV (p: 0.060) and PFV/ICV (p: 0.075) is obvious but not statistically significant (Table 4). Evaluation of the factors influencing presence of SM shows a statistically significant relation between SM and cerebellar descent length (p: 0.042), FMA (p ˂ 0.01), FMA/ICV (p ˂ 0.01), FMA/PFV (p ˂ 0.01) CoC-SO (p: 0.019), and Chiari subtypes (p ˂ 0.01). Statistically significant differences were detected in the relation between SM width and decision to operate (p: 0.010) and C–D angle (p ˂ 0.01).Although there Table 1 Demographic and morphometric analysis of the patient and control groups. CM Subtypes (N)

CM-0 (10)

CM-1 (45)

CM-1.5 (21)

CM-2 (15)

control (50)

Total (141)

Age (yrs) SM (mm) CD (mm) ICV (cm3) PFV (cm3) FMA (cm2) PFV/ICV FMA/PFV FMA/ICV LoC (mm) LoSO (mm) TS (˚) C-T angle (˚) C-SO angle (˚) CD angle (˚)

42.10 ± 18.495 4.54 ± 3.474

34.93 ± 15.185 6.7625 ± 3.235 8.282 ± 2.709 1180.715 ± 109.341 271.365 ± 35.792 8.659 ± 1.879 .229 ± 0.023 .0321 ± 0.006 .007 ± 0.001 37.073 ± 4.243 37.362 ± 5.755 47.524 ± 6.812 12.568 ± 7.227 96.317 ± 10.674 139.144 ± 10.182

37.38 ± 16.004 5.0714 ± 3.552 17.209 ± 6.756 1163.283 ± 134.052 264.088 ± 34.838 9.111 ± 1.900 .229 ± 0.037 .0348 ± 0.007 .007 ± 0.001 33.633 ± 5.813 34.585 ± 5.655 45.971 ± 5.823 11.004 ± 8.473 96.661 ± 8.656 135.947 ± 12.838

25.60 ± 17.927 6.8 ± 2.805 24.848 ± 8.838 1106.412 ± 176.403 222.409 ± 61.357 9.182 ± 1.571 .203 ± 0.044 .044 ± 0.014 .008 ± 0.002 30.36 ± 4.462 29.633 ± 4.507 49.82 ± 12.859 11.626 ± 6.668 89.7 ± 23.512 130.42 ± 12.875

40.14 ± 16.675

36.66 ± 16.766 5.8710 ± 3.337 13.664 ± 8.495 1142.817 ± 135.411 263.714 ± 39.698 8.872 ± 1.596 .232 ± 0.032 .0343 ± 0.008 .007 ± 0.00 35.114 ± 5.079 35.891 ± 5.778 47.509 ± 7.336 12.573 ± 7.490 91.536 ± 13.746 139.480 ± 11.575

1143.196 ± 209.302 263.180 ± 22.330 8.186 ± 0.707 .236 ± 0.039 .0313 ± 0.004 .007 ± 0.002 33.41 ± 6.591 37.55 ± 5.388 41.95 ± 5.740 12.95 ± 9.344 103.1 ± 15.228 138.42 ± 18.638

1110.959 ± 120.174 269.170 ± 32.912 9.008 ± 1.275 .243 ± 0.026 .044 ± 0.004 .008 ± 0.001 35.742 ± 4.208 36.662 ± 5.057 48.56 ± 5.905 13.444 ± 7.293 83.32 ± 8.773 144.198 ± 7.601

CM: Chiari malformation. N: number. Yrs: years. CD: cerebellar descent. SM: syringomyelia. ICV: intracerebral volüme. PFV: posterior fossa volüme. FMA: foramen magnum area. LoC: length of clivus. LoSO: length of supra-occiput. TS: tentorial slope. C–T angle: angle between clivus and tentorium. C-SO angle: angle between clivus and sub-occiput. C–D angle: clivodental angle.

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skull base), atlas, axis, and supporting ligaments. The PCF is rhomboid in shape; the floor of this rhomboid area is formed by the clivus, and the roof comprises the tentorium cerebelli and the mesencephalic aperture.

Table 2 Demographic and morphometric analysis of the patient in CM subtypes. Multiple Comparisons Dependent Variable

CM Subtype

CM Subtype

Mean Difference (IJ)

Std. Error

Sig.

PFV (cm3)

CMCMCMCMCMCMCMCMCMCMCMCMCMCMCMCMCMCMCM-

CM- 2 CM- 2 control CM- 2 CM- 2 CM- 2 CM- 2 control CM- 1.5 CM- 2 control CM- 2 CM- 2 control control control control control control

48.955* 41.678* −46.761* .025* −.012* −.012* −.009* .010* 3.440* 6.713* −5.382* 7.916* 7.728* −7.028* 19.780* 12.997* 13.341* −8.250* −13.778*

11.1704 12.6661 11.0299 0.0091 0.0030 0.0022 0.0025 0.0022 1.2424 1.4016 1.3840 2.1852 1.5958 1.5758 4.2124 2.4987 3.1621 2.8326 3.2068

0.000** 0.011* 0.000** 0.042* 0.000** 0.000** 0.002* 0.000** 0.049* 0.000** 0.001* 0.004* 0.000** 0.000** 0.000** 0.000** 0.000** 0.034* 0.000**

PFV/ICV FMA/PFV

LoC (mm)

LoSO (mm)

C-SO angle (˚)

CD angle (˚)

1 1.5 2 1 0 1 1.5 2 1 1 2 0 1 2 0 1 1.5 1.5 2

4.2. Pathophysiology of CM CM is the downward displacement of the caudal part of the cerebellum and/or medulla oblongata into the spinal canal [25]. While the pathogenesis of CM is not completely understood, it is thought that CM1 was genetically originated [26]. On previous studies CMs are thought to be arised from malfunctioning of chromosome 9 and 15 [27]. Chiari 1 malformation disorders are considered to arise from para-axial mesoderm origin [9]. Chiari 2, 3 and 4are thought to be arising from neuroectodermal origin [10]. Many investigators have sought to explain the pathogenesis of CM in terms of primary neural anomaly [28–30], but clinical and experimental studies indicate that the chronic tonsillar herniation observed in CM may result from overcrowding within a small and shallow primary PCF, caused by an underdeveloped occipital bone [23]. This is a consequence of raised intracranial pressure, with a varied etiology that includes hydrocephalus, space-occupying lesions, and a malformed posterior fossa. Correlating their findings with etiological factors, Milhorat et al suggested the following causal mechanisms: (1) cranial constriction; (2) cranial settling; (3) spinal cord tethering; (4) intracranial hypertension; and (5) intraspinal hypotension [31].

CM: CM- malformation. N: number. Yrs: years. CD: cerebellar descent. SM: syringomyelia. ICV: intracerebral volüme. PFV: posterior fossa volüme. FMA: foramen magnum area. LoC: length of clivus. LoSO: length of sub-occiput. TS: tentorial slope. C–T angle: angle between clivus and tentorium. C-SO angle: angle between clivus and supraa-occiput. C–D angle: clivo-dental angle. statistical sifnificance: * for ˂0.05. ** for ˂0.001.

4.3. Age and sex From a clinical point of view, CM can also be divided into adult and pediatric types [25]. In adults, CM is usually Type I and is most commonly seen after the second or third decade of life, with symptoms due to tightness of the posterior cranial fossa and/or to associated SM [23]. These are usually accompanied by bone anomalies such as basilar invagination but are less frequently associated with brain abnormalities other than herniation of the cerebellar tonsils. There are no populationbased studies on the incidence or prevalence of Chiari malformations in pediatric population. Chiari I and II are the most common types. Chiari III and IV are extremely rare. CM II malformation is usually seen in children and is characterized by congenital myeloschisis and brainstem

4. Discussion 4.1. Anatomy of the posterior fossa The posterior cranial fossa (PCF)is the most posterior part of the skull base and contains the brainstem, cranial nerves, and cerebellum. The floor of the PCF is formed by the basilar, condylar, and squamous parts of the occipital bone and the mastoid part of the temporal bone. The PCF’s roof is formed by the tentorium cerebelli, which is a fold of the dura. The CVJ is a collective term referring to the occiput (posterior Table 3 Multiple comparisons of morphometric measurements in CM subtypes. CASE GROUPS

p

SEX

p

Patient

Control

Male

Female

No Age (yrs) Mean, ± SD Sex CD (mm)Mean, ± SD SM (mm) Mean, ± SD ICV (cm3) Mean, ± SD PFV (cm3) Mean, ± SD FMA (cm2) Mean, ± SD PFV/ICV Mean, ± SD FMA/PFV Mean, ± SD FMA/ICV Mean, ± SD LoC (mm) Mean, ± SD LoSO (mm) Mean, ± SD TS (˚) Mean, ± SD C-T angle (˚) Mean ± SD C-SO angle (˚) Mean ± SD” CD angle (˚) Mean, ± SD

91 34,747253, ± 16,596916 63 M (69,2%), 28 F (30,8%) 13,664568, ± 8,495164 5,8710, ± 3,337171 1160,3219, ± 140,6649 260,7169, ± 42,8496 8,798292, ± 1,7497 0,226175, ± 0,033843 0,034664, ± 0,0094 0,007709, ± 0,0018 34,770330, ± 5,491377 35,468132, ± 6,123523 46,931868, ± 7,986403 12,094505, ± 7,592853 96,0516, ± 13,9250 136,8890, ± 12,5630

50 40,140000, ± 16,675792 38 M (76%), 12 F (24%)

40 31,275000, ± 17,868447

101 38,792079, ± 15,901143

,016*

13,595345, ± 8,285891 5,9434, ± 3,470502 1103,1270, ± 115,6263 257,7474, ± 35,4187 8,721765, ± 1,4674 0,235059, ± 0,033347 0,034489, ± 0,0083 0,008005, ± 0,0016 34,541584, ± 4,939762 35,918812, ± 5,224801 47,181188, ± 7,015664 12,547525, ± 7,087053 91,849505, ± 10,930925 139,471287, ± 10,253393

0,908 0,871 ,000** ,004* 0,074 0,106 0,673 0,102 0,033* 0,929 0,401 0,949 0,669 0,988

AGE (yrs)

CM subtypes SM localization ICV (cm3) PFV (cm3) C-T angle (˚)

1110,9598, ± 120,1744 269,1707, ± 32,9119 9,008817, ± 1,2756 0,243392, ± 0,026363 0,033659, ± 0,0044 0,008146, ± 0,0010 35,742000, ± 4,208742 36,662000, ± 5,057905 48,560000, ± 5,905411 13,444000, ± 7,293614 83,320000, ± 8,773197 144,198000, ± 7,601597

0,037* 0,22 0,45 0,002* 0,47 0,12 0,27 0,24 0,20 0,30 ˂0,001** ˂0,001**

13,839130, ± 9,192524 5,7600, ± 3,237901 1243,0364, ± 130,9991 278,7820, ± 45,9947 9,254680, ± 1,8482 0,225265, ± 0,028980 0,033850, ± 0,0073 0,007507, ± 0,0016 36,562500, ± 5,201710 35,822500, ± 7,060525 48,337500, ± 8,124881 12,637500, ± 8,520223 90,747500, ± 19,262438 139,505000, ± 14,541593

r −0,218 −0,369 0,261 −0,189 0,214

p 0,077 0,055 0,032* 0,048* 0,034*

No: number, Yrs: years, CD: cerebellar descent, SM: syringomyelia, ICV: intracerebral volüme, PFV: posterior fossa volüme, FMA: foramen magnum area, LoC: length of clivus, LoSO: length of supra-occiput, TS: tentorial slope, CT angle: angle between clivus and tentorium, C-SO angle: angle between clivus and supraa-occiput, CD angle: clivo-dental angle. Statistical significance: * for ˂0,05, ** for ˂0,001

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Table 4 Statistical analysis of SM groups in CM. r

p

SM occurrence

CD FMA FMA/PFV FMA/ICV C-SO angle

−0.184 −0.370 −0.274 −0.289 0.246

0.042* 0.000** 0.001** 0.006** 0.019*

SM width

Operation CD angle TS

0.414 −0.424 0.292

0.010** 0.008** 0.075

SM localization

SM width CD PFV/ICV FMA/PFV PFV Operation

0.195 −0.022 −0.143 0.094 −0.216 −0.293

Dependent Variable

SM localizations

Age (yrs) SM (mm)

cervicodorsal dorsal cervicodorsal

CD angle (˚) Operation

cervical cervical

dorsal cervical cervical dorsal cervicodorsal cervicodorsal

r

p

Operation

SM existence SM width ICV FMA PFV/ICV FMA/PFV FMA/ICV CD angle PFV

0.327 0.414 0.225 −0.410 −0.401 −0.173 −0.451 −0.264 −0.189

0.002** 0.010** 0.031* 0.000** 0.000** 0.026* 0.000** 0.015* 0.081

0.001** 0.028* 0.006** 0.014* 0.000** 0.057

Cerebellar descent

FMA FMA/PFV FMA/ICV LoC LoSO CD angle PFV/ICV PFV

0.209 0.282 0.187 −0.427 −0.355 −0.269 −0.199 −0.210

0.007* 0.001* 0.009* 0.000** 0.001** 0.015* 0.075 0.060

Mean Difference (I-J)

Std. Error

Sig.

7.989 8.901 1.036 1.349 4.487 .175

0.031* 0.048* 0.001** 0.042* 0.037* 0.038*

95% Confidence Interval Lower Bound Upper Bound 1.63 40.69 −43.66 −.14 1.805 6.876 .097 6.703 .574 22.514 −.88 −.02

*

21.158 −21.900* 4.340* 3.400* 11.544* −.450*

CD: cerebellar descent. SM: syringomyelia. ICV: intracerebral volüme. PFV: posterior fossa volüme. FMA: foramen magnum area. LoC: length of clivus. LoSO: length of supra-occiput. TS: tentorial slope. C–T angle: angle between clivus and tentorium. C-SO angle: angle between clivus and sub-occiput. C–D angle: clivo-dental angle. *:statistical significance for ˂0.05. **: statistical significance for ˂0.001.

4.4. Comparison of all patients and control groups

dysfunctionin early life [23].Typical features include a small posterior cranial fossa and neural abnormalities such as brainstem deformities and hydrocephalus [23]. As existing studies relate to well-defined subtypes, none has examined morphological changes with age.In their study of intracranial volume in pediatric patients, Sgouros et al reported a natural increase in ICV with age [32]. Furtado et al detected no morphological changes with age in either pediatric or adult patients [33]. Trigylidas et al compared two groups of children under the age of 18, comprising children aged 0–9 (group 1) and children aged 10–18 (group 2). They reported a statistically significant difference of PFV/ICV ratio in group 1,but no difference between group 2 patients and the control group [11]. A study examining differences between genders found that ICV was bigger in males [32].Studies of foramen magnum area have revealed that FMA is noticeably larger in males [34–37]. The present study differs from previous studies in that participants ranged in age from 2 to 67 years. This wide range in age enabled better evaluation of changes in the posterior fossa and CVJ over time. Onexamining changes in the healthy control group, we noticed first that FMA increases more obviously than PFVwhile LoSO shortens and C–D angle narrows. The changes in C–D angle mean that C-T angle decreases, leaving the clivus and tentorium in almost parallel positions. Examination of differences in the patient group facilitated understanding of developmental defects. In this patient group, the most notable diversification was in ICV, whichincreased with age (although it does not change in the control group). In the patient group, the occiput extends more inferiorly,leading to an increase in C-SO angle. A comparison between genders showed that ICV, PFV, and FMA are significantly larger in healthy male control subjects. In the patient group, ICVwasalso larger in males, but the difference between genders was more apparent. There wasno disparity in PFV, and the ratio of FMA/ICV was higher in females. We concluded that the difference in FMA/ICV ratio was due to narrower FMA in females than in males. Unlike healthy control subjects, LoC in the patient group was found to be slightly longer in males.

Although many previous studies haveexamined the morphology of the posterior fossa, most havefocused only on CM type 1 (CM-1).In some of these studies, PFV was found to be smaller in the patient group [11,23,31,33,38–41], but no difference in ICV was detected between groups [11,33,39,41]. In all of these studies, PFV/ICV ratio was found to be smaller in the patient group [11,33,39–41]; in some cases, LoC [23,31,39–46] and LoSO [23,31,39–41,43,44,47] were found to be smaller in the patient group.In studies with children,there was no difference between groups inLoC [33,47] or LoSO [33,42,46], and there wasno statistically significant difference between groupsin TS [11,40,44] or C–D angle [40]. In other studies, C–D angle was reported to be narrowerin the patient group [43,46]. One study from Turkey with CM-1 patients found that TS was larger in the patient group [44]. A study with CM-0 patients found that LoC was shorter in patients while TS was larger [48]. Another study involvingCM-2 patients found that LoC, LoSO, and PFV were smaller in the patient group [31], and FMA was found to be larger among patients [31]. The present study first compared the total patient group and the control group and also compared different subtypes of CM with each other, and with the control group. To the best of our knowledge, our study is unique in being the only one to subdivide the patient group according to CM subtypes. We found that while PFV did not differ for patient and control groups, patients’ ICV is larger, and their PFV/ICV ratio is therefore smaller; this finding correlates with those of earlier studies. Our findings show that C–D angle is narrower in patients, causing anteroinferior pressure on the brain stem. This is a clinically important result. We also found a larger angle in patients between the clivus and subocciput. On sagittal examination, the posterior fossa takes the form of a rhombus formed inferiorly by the clivus and subocciput and superiorly by the tentorium and tentorial aperture. Our findings show that the floor of this rhombus-shaped area is larger in patients, indicating that the structures in their posterior fossa have a larger base.

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The present study is also unique in comparing CM subtypes with a control group. Milhoratet al’s comparison of CM-2 with a control group is the only existing study to do so [31], finding that PFV, LoC, and LoSO were significantly smaller in CM-2 patients [31]. We also found that CM-2 patients had significantly smaller PFV, LoC, and LoSO than the control group or other CM subgroups. C-SO angle was found to be narrower than the control group in all patients other than CM-2.In light of these findings, it is reasonable to suggest that the morphological changes associated with CM are not congenital.

4.5. Comparison of Chiari subtypes with control group The differences between CM-1 patients and control group have been referred to above. C-SO angle was found to be wider in CM-0, CM-1 and CM-1.5 patients than in the control group. This is explained by the inferior tilt of the subocciput in CM-0 and CM-1 patients, which renders the posteroinferior part of the cerebellum more vulnerable to pressure from adjacent structures. In CM-1.5 patients, both clivus and subocciput displace more inferiorly. Most of the morphological changes seen in CM patients that differ from the control group are found among CM-2 patients; on examining these patients, PFV is found to be significantly smaller, and FMA/PFV ratio is therefore bigger. Additionally, LoC, LoSO and C–D angle are found smaller in patients with CM-2. As a result of these morphological changes, CM-2 patients have a very narrow space for the posterior fossa structures, and the risk of herniation increases in these cases as a consequence of a wide foramen magnum.

4.7. Cerebellar descent There is a close relationship between cerebellar descent (CD) length and Chiari subtype. In CM-0, there is no cerebellar tonsil or brain stem descent other than that associated with the syrinx [6]. In CM-1, there is caudal descent of the cerebellar tonsils [50], and in CM-1.5 cerebellar tonsil plus brain stem [7]. In CM-2, there is displacement of the medulla, fourth ventricle, and cerebellar vermis through the foramen magnum. Studies of tonsillar descent length and cranial morphometry are extremely rare. While Schady et al reported an inverse relationship between size of the posterior cranial fossa and degree of cerebellar herniation [51], Stovner et al found a strong positive correlation [52].On the other hand, Vurdem et al reported no relation between length of tonsillar herniation and PFV [38]. Dufton et al detected a negative correlation between CD and LoC [45].Some authors have reported a negative correlation between CD and SM [53,54] while others have reported a positive correlation [55,56]. Low brain stem position and severe tonsillar ectopia may induce crowding at the level of the foramen magnum, and a wide basal angle, short clivus, and acute clivoaxial angle may cause indentation and concomitant compression of the cervicomedullary junction. These pathoanatomical conditions lead to an increase in intramedullary pressure, causing brain stem dysfunction [53]. Because our study encompasses all subtypes of CM, the patient group includes both those with maximum CD (CM-2) and those without CD (CM-0). For that reason, our study is a good source of information on morphological changes occurring in the posterior fossa and CVJ during the course of disease. We show that crowding on the foramen magnum as a result of increased C–D angle also has an effect on craniocervical angle and FMA, as it affects the clivus and subocciput. CD and FMA increase as a result of an adaptation mechanism for the protection of neural structures. PFV decreases as C–D angle increases and volume of the posterior fossa diminishes. There is positive correlation between increase of degree in CD and FMA as crowding of CVJ, also ratios including FMA. However, there is negative correlation between LoC, LoSO, C–D angle, and PFV. It was also established that CD was shorter in patients with SM. These findings align with Yamazaki et al, who reported that patients with CM(whether associated with syringomyelia or not)exhibit more pronounced compression of the brain stem at the foramen magnum. Therefore, despite the blocked flow of cerebrospinal fluid at the foramen magnum, syrinx formation may be prevented because of severe compression [53].

4.6. Chiari subtypes CMs carry the same eponym, some are completely different disease entities. CM-0, 1 and 1.5 are associated with each other for their similarities in origin but CM-2 differs from them in respect to his origin. For this reason it may seem pointless to compare these two groups. But in our study we aimed to compare radiological differences and we thought that this comparison can be helpful in understanding all groups of disorders. CM-3 patients are not included in our study for having a bone defect. In the only study comparing Chiari subtypes,Milhoratet alcompared only CM-1 and CM-2;they reported that while LoC andLoSOwere shorter and PFVwas smaller in CM-1 and CM-2 patients, FMA was found to be wider in CM-2 patients [31].The essential reason for this difference is that cranial bony development after birth depends on a complex interplay of bony and neural factors, and neural development plays a key role in subsequent growth of the cranium [49].In the light of this finding, it is reasonable to suggest that tonsillar impaction of the FM may have been present early in development before closing of the foraminal sutures [31]. Given the complex pathology ofCM-2, the cause or causes of CD remain unknown. Possible pathogenic mechanisms include a lesion occurring with the primary neuroectodermal defect, spinal cord tethering by the caudally fixed myelomeningocele,hydrocephalus, or cerebrospinal fluid (CSF) leakage from the open neural tube [31]. Asthe first to report the differences between various CM subtypes and healthy participants, the present study may serve as a point of reference and for future studies. Between CM subtypes, ICV was found to be similar between groups but differed from the control group.As there are no existing studiesof this kind,we found no existing hypothesis that might explain these results. According to these results, volumetric changes begin with the onset of disease.The primary area for these morphological alterations is the posterior fossa;CM also affects CVJ, but the mechanism of these changes remains unknown, andfurther studies involving larger samples are needed to clarify its etiology. Obviously, alterations in the posterior fossa of CM patients are relevant over time. In CM-2, PFV is extremely narrow, and LoC and LoSOare very short. Because CM-2 is a congenital disease,it is suggested that the morphological changes due to the disease appear directly proportionalto time.Many of the morphological qualities of CM-2 differ from other subtypes, and one reason may be that basic changesin the posterior fossa and CVJ occur between the ages of 0 and 9 years. Milhoratet aloffered a partial explanationin their report [31], proposing that because cerebellar descent does not occur in CM-0 patients, the only observed morphological alteration is in C-SO angle. SM localization differs according to CM subtype. In CM-2, SM is found mostly in cervical and cervicodorsal areas. In CM-1, it is found mostly in the cervicodorsal area, and in the thoracal area in cases of CM-2. TSis 9˚ wider in CM-2 than in CM-1.

4.8. Syringomyelia features (existence, width and localization) SM is a disease characterized by fluid-cavitation of spinal cord segments. Specified information on the exact measure of how much widening on central canal is considered syringomyelia does not exist. Sometimes widenings of 1 or 2 mm are seen. Cavitation anddamage to the spinal cord (typically, the dorsal horn) results in abnormal processing of sensory input that manifests clinically asdysesthesia and pain. Possible causes for the formation of a syrinx inthe setting of a CMremain poorly understood. Syrinx development may be caused by increased cervical subarachnoid pulse pressure waves during brain expansion, with cardiac systole driving CSF into the spinal cord below the level of the lesion [57]. 9

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inform decision to operate. In cases of narrow PFV and FMA, the small C–D angle means that a straight craniocervical angle develops, leading to impairment of CSF in the central canal and the development or widening of SM, with corresponding appearance or deterioration of clinical signs. Based on these results, patients undergo surgical procedures. To our knowledge, there are no reports of prophylactic surgery based on morphologic evaluation of these patients prior to any clinical sign or symptom, and this seems worth exploring.

Comparing CM-1 patients with and without a syringomyelia, Yamazaki et al found lesser cerebellar descent, shorter LoC, and wider clivo-axial degree in patients with syringomyelia [53]. Crowding at the level of the foramen magnum may be induced by low brain stem position and severe tonsillar ectopia, and a wide basal angle, short clivus, and acute clivo-axial angle may cause indentation and concomitant compression of the cervicomedullary junction. Apparently, these pathoanatomical conditions cause an increase in intramedullary pressure, resulting in dysfunction of the brain stem [53]. These findings showthatpatients with CM not associated with syringomyelia have more pronounced compression of the brain stem at the foramen magnum. Therefore, despite blocking of the cerebrospinal fluid pathway at the foramen magnum, syrinx formation may be prevented by severe compression [53]. Halvorson et al found increased cerebellar descent in patients with syringomyelia but reported no difference in PFV,PFV/ICV, and FMA measures [55]. Yan et al. detected no morphometric alteration between groups with and without syringomyelia [43]. SM does not develop in every CM patient, but it is seen in most CM-1 patients and in all CM-0 patients. In light of the present findings, we would suggest that SM is less common among patients with a narrow FMA. As FMA enlarges, crowding of the CVJ by neural structures increases and, as explained by Yamazaki et al., this crowding affects CSF flow in the central canal and triggers SM formation. Beyond Yamazaki et al’sfindings, we detected an increase in C-SO angle, which is a risk factor for SM formation, and further studies are needed to understand this mechanism. Narrowing of C–D angle increases the width of SM. Cervicodorsal SM width was found to be wider than cervical or dorsal SM. It remains unclear how pressure on the syrinx cavity changes in different areas; if patients with a long segment cavity are subject to higher pressure and a long cavity therefore develops, it may be that higher cavity pressure causes a wider cavity area, but further studies will be needed to test this hypothesis. The risk for a cervically located SM increases as PFV narrows, and along with narrowing of C–D angle, the incidence of cervical SM increases. In addition, the risk for proximal SM also increases with enlargement of C–D angle. In all such cases, the decrease in PFV, narrowing of C–D angle, and increase in CD are found to be responsible for both the impairment of CSF and the increase in pressure in the central canal. As a result, the cervical area can be said to be the most enduring part of the central canal against pressure increase. SM is not found in the cervical area unless there is a severe increase in pressure.

5. Conlusion CM is divided into different subtypes for its various radiological and clinical features. On morphometric comparison of CM subtypes we concluded that etiological differences lead to morphological differences. CM-2 has remarkable differences both from other subtypes and from the control group. As for the other subtypes of CM basic difference they show from the control group is C-SO angle. Disclosure statement There is no conflict of interest. Ethic statement This study contains human subjects. References [1] H.B. Sarnat, P. Curatolo, Disorders of segmentation of the neural tube: Chiari malformations, Handb. Clin. Neurol. 87 (2007) 89–103. [2] P.W. Carmel, W.R. Markesbery, Early descriptions of the Arnold-Chiari malformation: the contribution of John Cleland, J. Neurosurg. 37 (1972) 543–547. [3] J. Pearce, Arnold Chiari, or “Cruveilhier cleland Chiari” malformation, J. Neurol., Neurosurg. Psychiatry 68 (2000) 13. [4] M. Loukas, N. Noordeh, M.M. Shoja, J. Pugh, W.J. Oakes, R.S. Tubbs, Hans Chiari (1851–1916), Child's Nerv. Syst. 24 (2008) 407–409. [5] I.-K. Kim, K.-C. Wang, I.-O. Kim, B.-K. Cho, Chiari 1.5 malformation: an advanced form of Chiari I malformation, J. Korean Neurosurg. Soc. 48 (2010) 375–379. [6] R.S. Tubbs, S. Elton, P. Grabb, S.E. Dockery, A.A. Bartolucci, W.J. Oakes, Analysis of the posterior fossa in children with the Chiari 0 malformation, Neurosurgery 48 (2001) 1050–1055. [7] R.S. Tubbs, B.J. Iskandar, A.A. Bartolucci, W.J. Oakes, A critical analysis of the Chiari 1.5 malformation, J. Neurosurg.: Pediatr. 101 (2004) 179–183. [8] B.J. Iskandar, G.L. Hedlund, P.A. Grabb, W.J. Oakes, The resolution of syringohydromyelia without hindbrain herniation after posterior fossa decompression, J. Neurosurg. 89 (1998) 212–216. [9] T.H. Milhorat, P.A. Bolognese, M. Nishikawa, N.B. McDonnell, C.A. Francomano, Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation type I in patients with hereditary disorders of connective tissue, J. Neurosurg. Spine. 7 (6) (2007) 601–609. [10] E. Schijman, History, anatomic forms, and pathogenesis of Chiari I malformations, Child’s Nerv. Syst. 20 (2004) 323–328. [11] T. Trigylidas, B. Baronia, M. Vassilyadi, E. Ventureyra, Posterior fossa dimension and volume estimates in pediatric patients with Chiari I malformations, Child’s Nerv. Syst. 24 (2008) 329–336. [12] M. Marin-Padilla, T.M. Marin-Padilla, Morphogenesis of experimentally induced Arnold-Chiari malformation, J. Neurol. Sci. 50 (1981) 29–55. [13] T.H. Milhorat, M.W. Chou, E.M. Trinidad, R.W. Kula, M. Mandell, C. Wolpert, M.C. Speer, Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients, Neurosurgery 44 (1999) 1005–1017. [14] R.S. Tubbs, M. Hill, M. Loukas, M.M. Shoja, W.J. Oakes, Volumetric analysis of the posterior cranial fossa in a family with four generations of the Chiari malformation type I, J. Neurosurg. Pediatr. 1 (1) (2008) 21–24. [15] G. Kanodia, V. Parihar, Y.R. Yadav, P.R. Bhatele, D. Sharma, Morphometric analysis of posterior fossa and foramen magnum, J. Neurosci. Rural Pract. 3 (2012) 261. [16] T.D. Holland, Sex determination of fragmentary crania by analysis of the cranial base, Am. J. Phys. Anthropol. 70 (1986) 203–208. [17] M. Graw, Morphometrische und morphognostische Geschlechtsdiagnostik an der menschlichen Schädelbasis, Osteologische Identifikation und Altersschätzung. Schmidt-Römhild, Lübeck (2001) 103–121. [18] J.D. Greenlee, K.A. Donovan, D.M. Hasan, A.H. Menezes, Chiari I malformation in the very young child: the spectrum of presentations and experience in 31 children under age 6 years, Pediatrics 110 (2002) 1212–1219. [19] N. Acer, M. Usanmaz, U. Tugay, T. Erteki, Estimation of cranial capacity in 17-26 years old university students/estimacion de la capacidad craneana en estudiantes universitarios entre 17 y 26 anos de edad, Int. J. Morphol. 25 (2007) 65–71. [20] K. Manjunath, Estimation of cranial volume-an overview of methodologies, J. Anat.

4.9. Operation The nature of the malformation and the degree of associated neurological impairments determines the management strategy for CMs. The decision to operate in cases of CM and SM must be planned according to neurological status and clinical signs or symptoms of the patient [1]. The goals of surgery for CM are to decompress the craniocervical junction and restore the normal flow of CSF in the region of the foramen magnum [58]. For this reason, the factors affecting the patient’s neurological and clinical status are very important in deciding to operate, as these radiological and morphological changes indicate the disease’s pathophysiology and prognosis. In a pediatric study of 49 individuals, Wu et al found a positive correlation between degree of tonsillar ectopia and severity of symptoms [59]. There was no significant difference in the degree of ectopia between the asymptomatic and symptomatic groups [11]. These findings complement an adult study by Elster and Chen, in which 31% of patients were asymptomatic and had variable tonsillar descent [60]. This suggests that tonsillar ectopia is a poor sole predictor for the development of symptoms and decision to perform surgery [61]. Not every CM patient undergoes surgery, which is planned in cases of clinical and neurological deterioration. Signs and symptoms requiring a surgical approach are found at higher rates among patients with small C–D angle, PFV, and FMA; the presence and width of SM also 10

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Soc. India 51 (2002) 85–91. [21] K. Manjunath, Estimation of cranial volume in dissecting room cadavers, J. Anat. Soc. India 51 (2002) 168–172. [22] L. Radinsky, Relative brain size: a new measure, Science 155 (1967) 836–838. [23] M. Nishikawa, H. Sakamoto, A. Hakuba, N. Nakanishi, Y. Inoue, Pathogenesis of Chiari malformation: a morphometric study of the posterior cranial fossa, J. Neurosurg. 86 (1997) 40–47. [24] A. Wackenheim, Roentgen Diagnosis of the Cranio-vertebral Junction, Springer, Berlin Heidelberg New York, 1974. [25] R.L. Friede, U. Roessmann, Chronic tonsillar herniation, Acta Neuropathol. 34 (1976) 219–235. [26] M.C. Speer, D.S. Enterline, L. Mehltretter, P. Hammock, J. Joseph, M. Dickerson, R.G. Ellenbogen, T.H. Milhorat, M.A. Hauser, T.M. George, Review article: Chiari type I malformation with or without syringomyelia: prevalence and genetics, J. Genet. Couns. 12 (2003) 297–311. [27] A.L. Boyles, D.S. Enterline, P.H. Hammock, D.G. Siegel, S.H. Slifer, L. Mehltretter, J.R. Gilbert, D. Hu-Lince, D. Stephan, U. Batzdorf, Phenotypic definition of Chiari type I malformation coupled with high‐density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15, Am. J. Med. Genet. A 140 (2006) 2776–2785. [28] A. Barry, B.M. Patten, B.H. Stewart, Possible factors in the development of the Arnold-Chiari malformation, J. Neurosurg. 14 (1957) 285–301. [29] W.J. Gardner, R.J. Goodall, The surgical treatment of Arnold-Chiari malformation in adults: an explanation of its mechanism and importance of encephalography in diagnosis, J. Neurosurg. 7 (1950) 199–206. [30] D. McLone, P. Knepper, The cause of Chiari II malformation: a unified theory, Pediatr. Neurosurg. 15 (1989) 1–12. [31] T.H. Milhorat, M. Nishikawa, R.W. Kula, Y.D. Dlugacz, Mechanisms of cerebellar tonsil herniation in patients with Chiari malformations as guide to clinical management, Acta Neurochir. 152 (2010) 1117–1127. [32] S. Sgouros, J.H. Goldin, A.D. Hockley, M.J. Wake, K. Natarajan, Intracranial volume change in childhood, J. Neurosurg. 91 (1999) 610–616. [33] S.V. Furtado, K. Reddy, A. Hegde, Posterior fossa morphometry in symptomatic pediatric and adult Chiari I malformation, J. Clin. Neurosci. 16 (2009) 1449–1454. [34] A. Uthman, N. Al-Rawi, J. Al-Timimi, Evaluation of foramen magnum in gender determination using helical CT scanning, Dentomaxillofac. Radiol. (2014). [35] C. Catalina-Herrera, Study of the anatomic metric values of the foramen magnum and its relation to sex, Cells Tissues Organs 130 (1987) 344–347. [36] A. Kumar, M. Dave, S. Anwar, Morphometric evaluation of foramen magnum in dry human skulls, Int. J. Anat. Res. 3 (2015) 1015–1023. [37] K.A. Murshed, A.E. Çiçekcibaşi, I. Tuncer, Morphometric evaluation of the foramen magnum and variations in its shape: a study on computerized tomographic images of normal adults, Turk. J. Med. Sci. 33 (2003) 301–306. [38] ÜE. Vurdem, N. Acer, T. Ertekin, A. Savranlar, M.F. Inci, Analysis of the volumes of the posterior cranial fossa, cerebellum, and herniated tonsils using the stereological methods in patients with Chiari type I malformation, Sci. World J. 2012 (2012). [39] S. Sgouros, M. Kountouri, K. Natarajan, Posterior fossa volume in children with Chiari malformation Type I, J. Neurosurg.: Pediatr. 105 (2006) 101–106. [40] O.A. Alkoç, A. Songur, O. Eser, M. Toktas, Y. Gönül, E. Esi, A. Haktanir, Stereological and morphometric analysis of MRI Chiari malformation Type-1, J. Korean Neurosurg. Soc. 58 (2015) 454–461. [41] N. Alperin, J.R. Loftus, C.J. Oliu, A.M. Bagci, S.H. Lee, B. Ertl-Wagner, B. Green, R. Sekula, Magnetic resonance imaging measures of posterior cranial fossa morphology and cerebrospinal fluid physiology in Chiari malformation type I, Neurosurgery 75 (2014) 515–522. [42] R. Noudel, N. Jovenin, C. Eap, B. Scherpereel, L. Pierot, P. Rousseaux, Incidence of

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50] [51] [52]

[53]

[54]

[55]

[56]

[57]

[58] [59] [60] [61]

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basioccipital hypoplasia in Chiari malformation type I: comparative morphometric study of the posterior cranial fossa: clinical article, J. Neurosurg. 111 (2009) 1046–1052. H. Yan, Z. Zhu, Z. Liu, B.-P. Qian, B. Wang, X. Sun, Y. Yu, F. Zhu, Y. Qiu, Morphometric features of posterior cranial fossa are different between Chiari I malformation with and without Syringomyelia, Glob. Spine J. 5 (2015) A015. F. Karagöz, N. Izgi, S.K. Sencer, Morphometric measurements of the cranium in patients with Chiari type I malformation and comparison with the normal population, Acta Neurochir. 144 (2002) 165–171. J.A. Dufton, S.Y. Habeeb, M.K. Heran, D.J. Mikulis, O. Islam, Posterior fossa measurements in patients with and without Chiari I malformation, Can. J. Neurol. Sci./ J. Canadien Des. Sci. Neurologiques 38 (2011) 452–455. H.S. Hwang, J.G. Moon, C.H. Kim, S.-M. Oh, J.-H. Song, J.H. Jeong, The comparative morphometric study of the posterior cranial fossa: what is effective approaches to the treatment of Chiari malformation type 1? J. Korean Neurosurg. Soc. 54 (2013) 405–410. A. Dagtekin, E. Avci, E. Kara, D. Uzmansel, O. Dagtekin, A. Koseoglu, D. Talas, C. Bagdatoglu, Posterior cranial fossa morphometry in symptomatic adult Chiari I malformation patients: comparative clinical and anatomical study, Clin. Neurol. Neurosurg. 113 (2011) 399–403. R.F. Sekula Jr, P.J. Jannetta, K.F. Casey, E.M. Marchan, L.K. Sekula, C.S. McCrady, Dimensions of the posterior fossa in patients symptomatic for Chiari I malformation but without cerebellar tonsillar descent, Cerebrospinal Fluid Res. 2 (2005) 1–7. F.C. Osuagwu, J.A. Lazareff, S. Rahman, S. Bash, Chiari I anatomy after ventriculoperitoneal shunting: posterior fossa volumetric evaluation with MRI, Child’s Nerv. Syst. 22 (2006) 1451–1456. M. Greenberg, Chiari malformation, Handbook of Neurosurgery, 6th ed., Thieme, New York, 2006, pp. 103–109. W. Schady, R. Metcalfe, P. Butler, The incidence of craniocervical bony anomalies in the adult Chiari malformation, J. Neurol. Sci. 82 (1987) 193–203. L. Stovner, U. Bergan, G. Nilsen, O. Sjaastad, Posterior cranial fossa dimensions in the Chiari I malformation: relation to pathogenesis and clinical presentation, Neuroradiology 35 (1993) 113–118. Y. Yamazaki, S. Tachibana, M. Takano, K. Fujii, Clinical and neuroimaging features of Chiari type I malformations with and without associated syringomyelia, Neurol. Med. Chir. (Tokyo) 38 (1998) 541–547. P.K. Pillay, I.A. Awad, J.R. Little, J.F. Hahn, Symptomatic Chiari malformation in adults: a new classification based on magnetic resonance imaging with clinical and prognostic significance, Neurosurgery 28 (1991) 639–645. K.G. Halvorson, R.T. Kellogg, K.N. Keachie, G.A. Grant, C.R. Muh, B. Waldau, Morphometric analysis of predictors of cervical syrinx formation in the setting of Chiari I malformation, Pediatr. Neurosurg. 51 (2016) 137–141. J. Strahle, K.M. Muraszko, J. Kapurch, J.R. Bapuraj, H.J. Garton, C.O. Maher, Chiari malformation Type I and syrinx in children undergoing magnetic resonance imaging: clinical article, J. Neurosur.: Pediatr. 8 (2011) 205–213. J.D. Heiss, K. Snyder, M.M. Peterson, N.J. Patronas, J.A. Butman, R.K. Smith, H.L. DeVroom, C.A. Sansur, E. Eskioglu, W.A. Kammerer, Pathophysiology of primary spinal syringomyelia, J. Neurosurg. Spine 17 (2012) 367. P. Pakzaban, Chiari Malformation, (2013) LINK-. –WEB-Accessed January 2013;27. Y. Wu, C. Chin, K. Chan, A. Barkovich, D. Ferriero, Pediatric Chiari I malformations Do clinical and radiologic features correlate? Neurology 53 (1999) 1271. A.D. Elster, M. Chen, Chiari I malformations: clinical and radiologic reappraisal, Radiology 183 (1992) 347–353. E.C. Ventureyra, H.A. Aziz, M. Vassilyadi, The role of cine flow MRI in children with Chiari I malformation, Child’s Nerv. Syst. 19 (2003) 109–113.