basilar invagination ( bi ) has many anonyms like cranial settling , vertical settling , vertical atlanto - axial subluxation and atlanto - axial impaction , and is defined as superior migration of the odontoid tip into the foramen magnum , leading to compression of the brainstem . bi prevalence may be not as rare as we thought before , although the prevalence of bi is less common than other spine diseases in general . mikulowski et al.9 ) showed that 11 ( 10% ) patients had unrecognized cord compression , which can be the cause of death in rheumatoid arthritis patients , and we also found 20 ( 8.2% ) patients with bi in 243 rheumatoid arthritis patients who were admitted to our hospital11 ) . however , no one - single method has been recommended to properly diagnose bi , due to the overlying structures on lateral plain radiographs . accordingly , we need to establish a more reliable and consistent method for early diagnosis of bi . the purpose of this study was to determine the inter - observer reliability and intra - observer repeatability of the methods for assessing the most appropriate measurement . we chose 22 bi patients ( female 16 , male 6 ) , who were confirmed by mri or ct as having bi . we selected other 25 patients ( female 17 , male 8) matching in age and sex as normal controls , using the electrical medical recording system . the average age of the study group was 67.2 ( bi group ) years and 67.6 ( control group ) years . the local research ethics committee waived the need for formal ethics approval for this retrospective study . only one cervical lateral standard radiograph per patient was saved in picture archiving communication system ( pacs ) by a senior neurosurgeon in a randomized order . thus , all data of the bi group and the control group were arranged in the same data folder . the most true - lateral of cervical spine radiographs was selected among many follow - up radiographs to reduce the super - imposition factor . three observers independently performed the measurement and checked the relevant anatomical landmarks and measuring technique before measuring without prior knowledge of the patients . time was not restricted in measuring the radiograph , and the measurement were done with an electric caliper in pacs . the radiographs were measured by each observer on two separate occasions with at least a two - month interval between measurements for removing the after - image effect . after - image effect can create a bias in the intra - observer measurement results , in particular . at the second evaluation , the radiographs were saved with a different numeric order to guard against any recall - bias . the results were tabulated for each observer and intra - observer as well as intra - observer agreement was assessed using the intraclass correlation coefficient ( icc ) test . we used six different measurements for the study and the measuring technique was followed as described by the original author 's paper . mcgregor line , mcrae line , chamberlain line , ranawat method , modified ( m)-ranawat method , and redlund - johnell method were included in this study . the following section explains the six different measurements in detail ( fig . 1 - 3 ) . mcgregor line : a line is drawn from the posterosuperior aspect of the hard palate to the most caudal point on the midline occipital curve . protrusion of the odontoid - tip above this line was represented with negative number7 ) . mcrae line : a line is drawn across the foramen magnum from the basion to the opisthion . protrusion of the odontoid - tip above this line was represented with a negative number8 ) . chamberlain line : a line is drawn from the posterior edge of the hard palate to the opisthion . protrusion of the odontoid - tip above this line was represented with a negative number1 ) . ranawat criterion : the distance between the center of the second cervical pedicle and the transverse axis of the atlas is measured along the axis of the odontoid process12 ) . modified ( m)-ranawat criterion : the distance between the midpoint of the base of c2 end - plate and a line from the center of the anterior arch of c1 to the center of the posterior arch6 ) . redlund - johnell method : the distance between the mcgregor line and the midpoint of the caudal margin of the second cervical vertebra body is measured13 ) . reliability was examined using icc score and their 95% confidence intervals . a p value smaller than 0.05 was considered significant . the icc ranged from 0 to 1 , where 0 represented no agreement and 1 perfect agreement . only one cervical lateral standard radiograph per patient was saved in picture archiving communication system ( pacs ) by a senior neurosurgeon in a randomized order . thus , all data of the bi group and the control group were arranged in the same data folder . the most true - lateral of cervical spine radiographs was selected among many follow - up radiographs to reduce the super - imposition factor . three observers independently performed the measurement and checked the relevant anatomical landmarks and measuring technique before measuring without prior knowledge of the patients . time was not restricted in measuring the radiograph , and the measurement were done with an electric caliper in pacs . the radiographs were measured by each observer on two separate occasions with at least a two - month interval between measurements for removing the after - image effect . after - image effect can create a bias in the intra - observer measurement results , in particular . at the second evaluation , the radiographs were saved with a different numeric order to guard against any recall - bias . the results were tabulated for each observer and intra - observer as well as intra - observer agreement was assessed using the intraclass correlation coefficient ( icc ) test . we used six different measurements for the study and the measuring technique was followed as described by the original author 's paper . mcgregor line , mcrae line , chamberlain line , ranawat method , modified ( m)-ranawat method , and redlund - johnell method were included in this study . the following section explains the six different measurements in detail ( fig . 1 - 3 ) . mcgregor line : a line is drawn from the posterosuperior aspect of the hard palate to the most caudal point on the midline occipital curve . protrusion of the odontoid - tip above this line was represented with negative number7 ) . mcrae line : a line is drawn across the foramen magnum from the basion to the opisthion . protrusion of the odontoid - tip above this line was represented with a negative number8 ) . chamberlain line : a line is drawn from the posterior edge of the hard palate to the opisthion . protrusion of the odontoid - tip above this line was represented with a negative number1 ) . ranawat criterion : the distance between the center of the second cervical pedicle and the transverse axis of the atlas is measured along the axis of the odontoid process12 ) . modified ( m)-ranawat criterion : the distance between the midpoint of the base of c2 end - plate and a line from the center of the anterior arch of c1 to the center of the posterior arch6 ) . redlund - johnell method : the distance between the mcgregor line and the midpoint of the caudal margin of the second cervical vertebra body is measured13 ) . reliability was examined using icc score and their 95% confidence intervals . a p value smaller than 0.05 was considered significant . the icc ranged from 0 to 1 , where 0 represented no agreement and 1 perfect agreement . icc score of all measurements was higher in the normal group than the bi pathology group , except in the chamberlain line method ( fig . redlund - johnell and m - ranawat had a highest icc score in both the normal and bi groups . mcrae line ( 0.21 ) had a lowest icc score in the normal group , and the ranawat method ( 0.18 ) had a lowest icc value in the bi pathology group . icc score of all measurements was higher in the normal group than bi group , except in the redlund - johnell method ( fig . the m - ranawat method ( 0.83 ) had a highest icc score in the normal group , and redlund - johenll method ( 0.80 ) had a highest icc score in the bi group . mcgregor line has a lowest icc score and a poor icc grade in both groups . icc score of all measurements was higher in the normal group than the bi pathology group , except in the chamberlain line method ( fig . redlund - johnell and m - ranawat had a highest icc score in both the normal and bi groups . mcrae line ( 0.21 ) had a lowest icc score in the normal group , and the ranawat method ( 0.18 ) had a lowest icc value in the bi pathology group . icc score of all measurements was higher in the normal group than bi group , except in the redlund - johnell method ( fig . the m - ranawat method ( 0.83 ) had a highest icc score in the normal group , and redlund - johenll method ( 0.80 ) had a highest icc score in the bi group . mcgregor line has a lowest icc score and a poor icc grade in both groups . having many methods for the diagnosis of bi can imply that it is very difficult to choose just one particular method in clinical circumstances . first , anatomical landmark may be ambiguous , thus leading the interpreter to measure different results . second , measurement error can be made by the interpreter himself or on the radiographs . the lack of confidence in anatomic landmarks can make unreliable results and it is hard to obtain the absolute true - lateral radiographs in every patients . therefore it is very important for us to determine how reliable , reproducible these measurements are . we verified the reliability and reproducibility among various measurement techniques with inter - observer and intra - observer correlation studies . this study was performed using six - different methods , excluding clark station2 ) , kauppi et al.4 ) , and wackenheim line method , because these methods can not represent numerical value , so it will be useless in the present inter - observer and intra - observer reliability test . also , wackenheim line has been shown to have low specificity in many reports14 ) . revealed that the reason that dorsal surface of clivus is rarely a straight line , unlike its appearance on radiographs6 ) . first , icc score will be higher in the normal group than the bi group , because the normal group has relatively precise anatomic landmarks than the bi groups . second , intra - observer correlation may gain the upper hand than inter - observer correlation . third , shared anatomic landmarks between many diagnostic methods may be the key to make the similar pattern of results . for example , the c1 arch is the key between ranwat and m - ranawat and the opsthion is the key between mcrae and chamberlain . the caudal point of the occipital curve is the key between mcgregor and redlund - johnell , the midpoint of the base of c2 endplate is the key between redlund - johnell and m - ranawat method . the odontoid tip is the key in mcgregor , mcrae and chamberlain line method . generally , the intra - observer correlation value was higher than inter - observer correlation in our study , which was consistent with our assumption . intra - observer reproducibility was related to consistency for measuring pattern in each observer in determining the anatomic landmarks and using the pacs system . therefore , all observers had their own specific measuring pattern , although it is very difficult to identify the most correct pattern . if we can re - examine the measuring process with all examined radiographs , which remained with the electrical trace , it will be a good opportunity to increase the inter - observer correlation and reduce the error . odontoid - tip based measurement ( mcgregor line , mcrae line , chamberlain line ) had a low icc score than other measurements with the inter - observer test . many reports showed similar results like the results of the present study , stating the difficulty in identifying the odontoid - tip14 ) . the odontoid - tip is not clearly visible on standard radiographs , especially with old age or rheumatoid arthritis patients , due to erosion , overlying mastoid process and osteoporosis . we conducted bone densitometry and the mean t - score was -2.27 ( range , -3.9 - -0.7 ) in the bi group and the mean value of t - score was -1.49 ( range , -2.3 - -0.4 ) in the normal group . more severe osteoporotic patterns were confirmed in the bi group , which can induce the low icc score in the bi group than the normal group . the opisthion may be the ambiguous landmark in the inter - observer test , and this reason can be explained by the following clue . first , the icc score was reversed only in the chamberlain line method between the bi group ( 42.6 ) and the normal group ( 25.7 ) . second , mcrae has a lowest icc score in both study groups ( except in the bi group ) . a super - imposition factor , induced by relative globular form of skull base , may be the main reason for the above results . we also must consider the basion as an important attributable factor in lowering the icc score in the mcrae line method3 ) . many previous studies showed that the ranawat method has good sensitivity and may be the one of the best diagnostic tools5,14 ) . however , the ranawat method showed a lower icc score ( the fourth position in normal , the last position in bi group ) in our study than expected . riew et al.14 ) showed that combination of clark station , redlund - jonhell and ranawat method gave high sensitivity ( 94% ) and negative predictive value ( 91% ) . if , we assume that the c1 arch is a good landmark by comparing the high icc score in the redlund - johnell and m - ranawat methods , the center of the second cervical pedicle may be the ambiguous landmark . a great difference in the icc score between the ranawat and m - ranawat methods c1 - 2 facet joint destruction was one of the pathophysiologies in basilar invagination and osteoporotic change of the c2 pedicle may be the reason for the results . in addition , the cortical margin of the c2 pedicle was not in an absolute globular form , which can make the observer difficult to decide the exact center point . redlund - johnell and m - ranawat has a highest icc score in both groups . therefore , the midpoint of the caudal margin of the second cervical vertebra body may be the most reliable landmark for the diagnosis of bi pathology , as mentioned above . vertebral body has relative a plane figure anatomically than other structures and there was no interfering bony structure near the surrounding . the redlund - johnell , ranawat method and m - ranawat method are measures of the spatial relationship between c1 and c2 rather than the more critical occiput - c2 relationship6 ) . basically , basilar invagination pathophysiologic consequence was mainly induced by c1 - 2 articulation than occiput - c110 ) . only the mcgregor line has showed the decreasing pattern in the icc score , between the inter - observer and the intra - observer test . redlund - johnell method also has the reversed icc score between inter - observer ( 91.7 ) and intra - observer ( 71.1 ) test in normal group . these above findings can imply that the caudal point on the midline occipital curve may also be an ambiguous landmark . the ranawat method had a relatively higher icc score than the inter - observer test . although it is difficult to assure exact the reason , different measuring patterns may exist by individuals , in a similar manner as individual variations in the locations of the center of the second cervical pedicle , and parallel to the axis odontoid - process . mcgregor test has a lowest icc score compared to other odontoid - tip based methods in our study . anatomically , mcgregor line has the nearest position to the odontoid - tip compared to other methods , which can induce difficulty in the precise of the electric caliper . unlike pencils , electrical caliper is operated by cursor - controlled by mouse and magnifying degree is not fixed and strictly regulated . the less the short distance measured with inaccuracy , the less the correlation score we obtain . redlund - johnell and m - ranawat methods were shown to have the highest icc score in both groups , as with the inter - observer study . all three observers differed in medical standing , one was a senior spine - neurosurgeon ( highly experienced ) and the others were junior spine - neurosurgeon ( less experienced ) . the observer - bias could be included , even though three observers tried to reduce the problem with prior consent about anatomical landmarks and measuring technique considerably . as mentioned before , consensus on how to use the software system ( pacs ) was strictly regulated in this study . however , the degree of magnification and the pattern of using the electric caliper were variable , which can attribute to some degree of measuring bias . we also could not hold a conviction with the standardization for neck position , thus occipito - cervical angle and the degree of flexion or extension can be variable in each patient . the degree of measurement in each diagnostic method can be influenced by the neck position and occipito - cervical angle . intra- as well as inter - observer reliability are connected to the concept of consistency , which is defined as the agreement of two quantitative measurements where neither one is assumed ' correct ' . therefore , our results may not show the correctness of the methods exactly , but provided some positive contributions . first , these results can open our eyes to the fact that we always must consider the lack of stability in our measuring technique . second , icc score may suggest the most reliable anatomic landmark , which may help us to find the best combination of methods , so that not to miss the basilar invagination . although our study revealed that odontoid - tip based measurements have low icc score , these measurement can be useful in a ct based - study , which can show the odontoid - tip more accurately . opisthion and caudal point of the midline occipital curve based measurements can be also significant with efforts to obtain the true - lateral radiographs . odontoid - tip based measurement ( mcgregor line , mcrae line , chamberlain line ) had a low icc score than other measurements with the inter - observer test . many reports showed similar results like the results of the present study , stating the difficulty in identifying the odontoid - tip14 ) . the odontoid - tip is not clearly visible on standard radiographs , especially with old age or rheumatoid arthritis patients , due to erosion , overlying mastoid process and osteoporosis . we conducted bone densitometry and the mean t - score was -2.27 ( range , -3.9 - -0.7 ) in the bi group and the mean value of t - score was -1.49 ( range , -2.3 - -0.4 ) in the normal group . more severe osteoporotic patterns were confirmed in the bi group , which can induce the low icc score in the bi group than the normal group . the opisthion may be the ambiguous landmark in the inter - observer test , and this reason can be explained by the following clue . first , the icc score was reversed only in the chamberlain line method between the bi group ( 42.6 ) and the normal group ( 25.7 ) . second , mcrae has a lowest icc score in both study groups ( except in the bi group ) . a super - imposition factor , induced by relative globular form of skull base , may be the main reason for the above results . we also must consider the basion as an important attributable factor in lowering the icc score in the mcrae line method3 ) . many previous studies showed that the ranawat method has good sensitivity and may be the one of the best diagnostic tools5,14 ) . however , the ranawat method showed a lower icc score ( the fourth position in normal , the last position in bi group ) in our study than expected . riew et al.14 ) showed that combination of clark station , redlund - jonhell and ranawat method gave high sensitivity ( 94% ) and negative predictive value ( 91% ) . if , we assume that the c1 arch is a good landmark by comparing the high icc score in the redlund - johnell and m - ranawat methods , the center of the second cervical pedicle may be the ambiguous landmark . a great difference in the icc score between the ranawat and m - ranawat methods c1 - 2 facet joint destruction was one of the pathophysiologies in basilar invagination and osteoporotic change of the c2 pedicle may be the reason for the results . in addition , the cortical margin of the c2 pedicle was not in an absolute globular form , which can make the observer difficult to decide the exact center point . redlund - johnell and m - ranawat has a highest icc score in both groups . therefore , the midpoint of the caudal margin of the second cervical vertebra body may be the most reliable landmark for the diagnosis of bi pathology , as mentioned above . vertebral body has relative a plane figure anatomically than other structures and there was no interfering bony structure near the surrounding . the redlund - johnell , ranawat method and m - ranawat method are measures of the spatial relationship between c1 and c2 rather than the more critical occiput - c2 relationship6 ) . basically , basilar invagination pathophysiologic consequence was mainly induced by c1 - 2 articulation than occiput - c110 ) . only the mcgregor line has showed the decreasing pattern in the icc score , between the inter - observer and the intra - observer test . redlund - johnell method also has the reversed icc score between inter - observer ( 91.7 ) and intra - observer ( 71.1 ) test in normal group . these above findings can imply that the caudal point on the midline occipital curve may also be an ambiguous landmark . the ranawat method had a relatively higher icc score than the inter - observer test . although it is difficult to assure exact the reason , different measuring patterns may exist by individuals , in a similar manner as individual variations in the locations of the center of the second cervical pedicle , and parallel to the axis odontoid - process . mcgregor test has a lowest icc score compared to other odontoid - tip based methods in our study . anatomically , mcgregor line has the nearest position to the odontoid - tip compared to other methods , which can induce difficulty in the precise of the electric caliper . unlike pencils , electrical caliper is operated by cursor - controlled by mouse and magnifying degree is not fixed and strictly regulated . the less the short distance measured with inaccuracy , the less the correlation score we obtain . redlund - johnell and m - ranawat methods were shown to have the highest icc score in both groups , as with the inter - observer study . all three observers differed in medical standing , one was a senior spine - neurosurgeon ( highly experienced ) and the others were junior spine - neurosurgeon ( less experienced ) . the observer - bias could be included , even though three observers tried to reduce the problem with prior consent about anatomical landmarks and measuring technique considerably . as mentioned before , consensus on how to use the software system ( pacs ) was strictly regulated in this study . however , the degree of magnification and the pattern of using the electric caliper were variable , which can attribute to some degree of measuring bias . we also could not hold a conviction with the standardization for neck position , thus occipito - cervical angle and the degree of flexion or extension can be variable in each patient . the degree of measurement in each diagnostic method can be influenced by the neck position and occipito - cervical angle . intra- as well as inter - observer reliability are connected to the concept of consistency , which is defined as the agreement of two quantitative measurements where neither one is assumed ' correct ' . therefore , our results may not show the correctness of the methods exactly , but provided some positive contributions . first , these results can open our eyes to the fact that we always must consider the lack of stability in our measuring technique . second , icc score may suggest the most reliable anatomic landmark , which may help us to find the best combination of methods , so that not to miss the basilar invagination . although our study revealed that odontoid - tip based measurements have low icc score , these measurement can be useful in a ct based - study , which can show the odontoid - tip more accurately . opisthion and caudal point of the midline occipital curve based measurements can be also significant with efforts to obtain the true - lateral radiographs . thus , the center of the c2 pedicle may no longer be a reliable anatomical landmark , which is a different conclusion from other previous studies . odontoid - tip based method is not a reliable method as revealed by many previous reports . redlund - johnell and m - ranawat are the most reliable methods , thus c1 arch and c2 endplate may be the most reliable anatomical landmarks .
objectivethis study was designed to determine the most reliable cephalometric measurement technique in the normal population and patients with basilar invagination ( bi).methodstwenty - two lateral radiographs of bi patients and 25 lateral cervical radiographs of the age , sex - matched normal population were selected and measured on two separate occasions by three spine surgeons using six different measurements . statistical analysis including intraclass correlation coefficient ( icc ) was carried out using the spss software ( v. 12.0).resultsredlund - johnell and modified ( m)-ranawat had a highest icc score in both the normal and bi groups in the inter - observer study . the m - ranawat method ( 0.83 ) 
 had a highest icc score in the normal group , and the redlund - johenll method ( 0.80 ) had a highest icc score in the bi group in the intra - observer test . 
 the mcgregor line had a lowest icc score and a poor icc grade in both groups in the intra - observer study . 
 generally , the measurement method using the odontoid process did not produce consistent results due to inter and intra - observer differences in determining the position of the odontoid tip . 
 opisthion and caudal point of the occipital midline curve are somewhat ambiguous landmarks , which induce variable icc scores.conclusionon the contrary to other studies , ranawat method had a lower icc score in the inter - observer study . 
 c2 end - plate and c1 arch can be the most reliable anatomical landmarks .