|Year : 2015 | Volume
| Issue : 1 | Page : 19-27
Ocular motor tests in relapsing remitting multiple sclerosis
Hesham Mohamed Negm1, Mohamed Ibrahim Shabana2, Hatem Samir Mohamed Shehata3
1 Otorhinolaryngology Department, Kasr Al-Aini Cairo University Hospitals, Cairo, Egypt
2 Audiology Unit, Kasr Al-Aini Cairo University Hospitals, Cairo, Egypt
3 Neurology Department, Kasr Al-Aini Cairo University Hospitals, Cairo, Egypt
|Date of Submission||17-Mar-2015|
|Date of Acceptance||10-May-2015|
|Date of Web Publication||15-Jun-2015|
Mohamed Ibrahim Shabana
Audiology Unit, Otolaryngology Department, Kasr Al-Aini Cairo University Hospitals, 110 a 26th July Street, Zamalek Cairo 11211
Source of Support: None, Conflict of Interest: None
Multiple sclerosis (MS) is the quintessential neurologic disorder from which one can gain insights into the principles of afferent and efferent neuro-ophthalmology. The popularity of eye movements as an experimental tool can be partly attributed to the fact that they can be conveniently and accurately measured and analyzed, and also because much is known about their neural substrate. It is therefore no surprise that eye movements have been commonly applied to better understand the visual and motor disorders in patients with MS.
The aim of this study was to demonstrate the vast ocular motor abnormalities that occur in this disease using videonystagmography as our tool of description and determine the relationship with Expanded Disability Status Scale (EDSS) and MRI findings.
Materials and methods
The current study included 76 patients who were divided into two groups. Group I comprised 54 patients with relapsing-remitting multiple sclerosis who fulfilled the Revised Mcdonald's criteria for diagnosis of MS. The age of the patients in group I ranged from 20 to 68 years, with a mean of 35.13 ± 9.42 SD (23 men and 31 women). Group II comprised 22 healthy age-matched and sex-matched individuals who were recruited from the general population and were not relatives of the patients. Their ages ranged from 19 to 54 years, with a mean of 33.81 years ± 10.07 SD (11 men and 11 women). Video-nystagmography, saccadic tracking, random horizontal saccades, optokinetic tracking (at 20, 40, and 60/s), smooth pursuit (0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz), and gaze-evoked nystagmus were examined in both groups. Group I, in addition, was subjected to a thorough neurological history and neurological examination, EDSS assessment, ophthalmologic examination (visual acuity and ocular motility), and radiological assessment by MRI with and without contrast.
The eye movement disorders most commonly noted are saccadic dysmetria, followed by gaze-evoked nystagmus and pendular nystagmus. They are caused by disease affecting the brain stem and cerebellar circuits. Reduced pursuit gain and saccadic pursuit were also noted. A strong correlation between brainstem and cerebellar MRI lesions and the affection of the ocular motor system was well noted. A high EDSS score was well correlated with abnormal ocular motor test findings.
Ocular motor system tests are more sensitive than conventional clinical examinations in identifying abnormalities in MS.
Keywords: Expanded Disability Status Scale, multiple sclerosis, optokinetic, saccades, smooth pursuit
|How to cite this article:|
Negm HM, Shabana MI, Shehata HS. Ocular motor tests in relapsing remitting multiple sclerosis. Adv Arab Acad Audio-Vestibul J 2015;2:19-27
|How to cite this URL:|
Negm HM, Shabana MI, Shehata HS. Ocular motor tests in relapsing remitting multiple sclerosis. Adv Arab Acad Audio-Vestibul J [serial online] 2015 [cited 2019 Jun 17];2:19-27. Available from: http://www.aaj.eg.net/text.asp?2015/2/1/19/158728
| Introduction|| |
The basic function of the ocular motility system is to maintain an area of interest on the fovea. The supranuclear pathways of the cortex and brainstem control the actions of the ocular motor nerves. Injury to supranuclear structures usually results in disorders of conjugate gaze and impairment of the slow and fast eye movement systems. In contrast, infranuclear injury to the ocular motor system results in misalignment of the eyes and double vision. Binocular double vision usually indicates a process involving the nerve, neuromuscular junction, or muscle, whereas monocular diplopia suggests an ocular etiology. Abnormal eye movements (AEMs) may result in disorders of fixation leading to the development of nystagmus and saccadic oscillations  .
There are four types of eye movements that are of particular interest in the evaluation of balance. Saccades, the fastest of eye movements, enable us to rapidly redirect our line of sight. Pursuit is the smooth following of moving objects to stabilize their image upon the fovea. Optokinetic nystagmus is the eye movement evoked by following of moving fields. Fixation is the eye movement associated with an effort to keep the eyes completely still.
| Rationale|| |
The testing of ocular motor functions is an important step in the diagnosis of vestibular and balance disorders for three reasons: first, most of these disorders are associated with disorders of eye movements. Second, the classification of the eye movement disorder will often lead to localization of the neural structures involved. Third, eye movement disorders can cause impaired vision or dizziness and thus might impair balance  . Abnormalities in ocular motor tests recorded by videonystagmography (VNG) may indicate central vestibular system impairment  . Those abnormalities have been common findings in earlier studies on MS. They vary considerably from 5 to 80% depending not only on the method used but also on the MS material selected. Thus, the key question is, what are the best methods to identify the numerous lesions in the ENT region?  . The rationale of this study is to demonstrate the vast ocular motor abnormalities that occur in this disease using VNG as our tool of description.
| Aim of the study|| |
The study aimed to determine the different ocular motor test findings in relapsing-remitting multiple sclerosis (RRMS) and compare them with the normal control group and whether an examination that specifically tests saccades and vestibular eye movements is more sensitive than conventional clinical examinations in identifying brainstem and cerebellar dysfunction in MS. Statistical correlations between the different MS subgroups and their ocular motor test findings were also ascertained:
(1) Correlation between brainstem and cerebellar MRI lesion subgroups with regard to pursuit gain, pursuit catch-up saccades, OKN gain, saccades latency, saccades speed, and saccades accuracy.
(2) Correlation between pendular nystagmus and gaze-evoked nystagmus subgroups with regard to pursuit gain, pursuit catch-up saccades, OKN gain, saccades latency, saccades speed, and saccades accuracy.
(3) Correlation between Expanded Disability Status Scale (EDSS) score and pursuit gain, pursuit catch-up saccades, optokinetic nystagmus (OKN) gain, saccades latency, saccades speed, and saccades accuracy.
| Materials and methods|| |
The current study is a case-controlled trial that was conducted from February 2014 until August 2014. It included 76 Egyptian patients.
The patient group
This group comprised 54 patients with RRMS who fulfilled the Revised Mcdonald's criteria  for diagnosis of multiple sclerosis (MS), where relapse is defined as the occurrence of a new neurological disturbance for a duration of at least 24 h. Patients were diagnosed and their follow-up was performed at the neurology department of Kasr Al-Ainy Hospital.
The control group
This group comprised 22 healthy age-matched and sex-matched individuals.
| Methods|| |
The MS patients were subjected to the following:
- Full history taking according to the standard Neurology sheet of Kasr Al-Ainy Neurology department.
- Full neurological examination.
- Opthalmologic examination (visual acuity and ocular motility).
- Radiological assessment with MRI, with and without contrast , using a 1.5 T unit Intera Philips medical system at the Radiology department of Kasr Al-Ainy Hospital. Axial T1, T2, and FLAIR images were acquired, which were assessed by an experienced radiologist for the following:
- Diagnosis of MS according to Revised Mcdonald's criteria  and Barkhof criteria for dissemination in space , .
- The number of black holes, which is defined as any hypotense region visible on T1-weighted images coincident with a region of high signal intensity on T2-weighted images  . The black holes have been shown to be areas of axonal loss on histopathology  .
- Assessment of disease severity by EDSS  , which is a standardized neurological examination and assessment scale for evaluation of neurological disability in MS patients. The EDSS includes the assessment of seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, or mental functions).
- VNG (both for the MS group and the control group) using DIFRA Instrumentation VISIOSTAR II, software Disoft version 1.30.04, NYSSTAR I camera. Windows 7 Ultimate, Processor Intel Core i3-2120 CPU @ 3.30GHz. RAM 4GB, 32-bit Operating system.
- Saccadic tracking: random horizontal saccades (measuring latency, speed, and accuracy), elicited by visual dots presented at random frequency, alternating between 15 and 30° horizontal positions to the right or the left.
- Optokinetic tracking at 20, 40, and 60°/s (measuring gain, and ratio of field velocity to eye velocity). A whole moving field directed by an overhead projector is used at the three designated speeds.
- Smooth pursuit, elicited by a dot moving sinusoidal in the horizontal plane (amplitude: 30°) to the right and left at 0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz (measuring gain and inaccuracy being determined by the presence of corrective saccades). The pursuit gain (measured at each frequency) is considered abnormal when the eye does not match the target velocity during a series of regular to and fro movements (the morphology of test recordings was also taken into the consideration. Each initially abnormal result was repeated to achieve optimal performance), and corrective (catch-up) saccades, saccadic pursuit, and asymmetry are observed. According to published normative data  , smooth pursuit gain lower than 0.60 is considered pathological.
- Gaze-evoked nystagmus: Patients fixed their gaze on a target 30° to the right, 30° to the left, and in the center position. Any sustained nystagmus that occurred under these conditions was regarded as pathological.
| Results|| |
[Table 1] shows the demographic and clinical data of the patients. A statistically significant difference was found between group I and group II as regards OKN 20° gain (P = 0.043), OKN 40° gain (P < 0.001), OKN 60° gain (P < 0.001) ([Table 2]), 0.2 Hz pursuit gain (P = 0.031), 0.3 Hz pursuit gain (P = 0.032), 0.4 Hz pursuit gain (P < 0.046), 0.5 Hz pursuit gain (P < 0.034), 0.6 Hz pursuit gain (P < 0.006), and 0.7 Hz pursuit gain (P < 0.001), all of which were lower in group I ([Table 3] and [Figure 1]).
A statistically significant difference was found between group I and group II as regards 0.2 Hz pursuit catch-up saccades (P = 0.011), 0.3 Hz pursuit catch-up saccades (P = 0.019), 0.4 Hz pursuit catch-up saccades (P = 0.019), 0.5 Hz pursuit catch-up saccades (P < 0.005), 0.6 Hz pursuit catch-up saccades (P < 0.007), and 0.7 Hz pursuit catch-up saccades (P < 0.004), which were higher in group I ([Table 4] and [Figure 2]).
|Table 4 Comparison between group I and group II as regards pursuit catch-up saccades|
Click here to view
A statistically significant difference was found between group I and group II as regards saccades latency (P = 0.016), which was increased in group I. A statistically significant difference was found between group I and group II as regards saccades speed (P = 0.007) and saccades accuracy (P = 0.016), which were reduced in group I ([Table 5] and [Figure 3]).
|Table 5 Comparison between group I and group II as regards saccades latency, speed, accuarcy|
Click here to view
A statistically significant difference was found between patients with acquired pendular nystagmus and patients without acquired pendular nystagmus regarding OKN gain (P = 0.013), pursuit gain (P = 0.046), pursuit catch-up saccades (P = 0.022), saccades speed (P = 0.007), saccades accuracy (P = 0.041), and saccades latency (P = 0.034), which were worse in patients with acquired pendular nystagmus ([Table 6] and [Figure 4]). A statistically significant difference was found between patients with gaze-evoked nystagmus and patients without gaze-evoked nystagmus regarding OKN gain (P = 0.028), pursuit gain (P = 0.022), pursuit catch-up saccades (P = 0.049), saccades speed (P = 0.0497), saccades accuracy (P = 0.04), and saccades latency (P = 0.025), which were worse in patients with gaze-evoked nystagmus ([Table 7]).
|Table 7 Comparison between patients with and without gaze-evoked nystagmus|
Click here to view
A statistically significant difference was found between patients with cerebellar and brainstem MRI lesions and patients without cerebellar and brainstem MRI lesions regarding OKN gain (P < 0.001), pursuit gain (P = 0.033), pursuit catch-up saccades (P = 0.04), saccades latency (P = 0.036), saccades speed (P = 0.043), and saccades accuracy (P = 0.032), which were worse in patients with cerebellar and brainstem MRI lesions. A strong correlation was revealed between infratentorial brain volume (cerebellar and brainstem) and abnormal ocular motor (AOM) eye movements ([Table 8]).
No statistically significant difference was found between patients with cerebellar MRI lesions and patients with brainstem MRI lesions ([Table 9]). No statistically significant difference was found between patients treated with solumedrol alone versus patients treated with solumedrol and another prophylactic drug (Azathioprine, Methotrexate, Synacthen, Cyclophosphamide, Interferon β1b)
|Table 9 Comparison between patients with cerebellar MRI lesions versus with brainstem MRI lesions|
Click here to view
A statistically significantly negative correlation was found between pursuit gain (0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz) and EDSS score with r equal to −0.3, −0.29, −0.31, −0.35, −0.33, and −0.22 and P equal to 0.035, 0.04, 0.03, 0.039, 0.049, and 0.044 ([Table 10] and [Figure 5]). A statistically significantly positive correlation was found between pursuit catch-up saccades (0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz) and EDSS score with r equal to 0.38, 0.44, 0.37, 0.33, 0.33, and 0.29 and P equal to 0.018, 0.046, 0.036, 0.04, 0.028, and 0.045. A statistically significantly negative correlation was found between OKN gain (20, 40, 60°) and EDSS score with r equal to −0.39, −0.287, and −0.246 and P equal to 0.027, 0.03, and 0.029. A statistically significantly positive correlation was found between saccades latency and EDSS score (r = 0.233, P = 0.029). A statistically significantly negative correlation was found between saccades speed, accuracy, and EDSS score (r = −0.304 and −0.321 and P = 0.026 and 0.018).
|Table 10 Correlation between smooth pursuit gain and Expanded Disability Status Scale|
Click here to view
| Discussion|| |
In the present study, saccadic testing revealed a statistically significant difference between group I (study group) and group II (control group). Supporting our study, Downey et al.  reported that the most common abnormality was saccadic dysmetria, taking the form of either overshoots (hypermetria) or an inappropriate vector (e.g. requiring a vertical correction following a horizontal saccade). Serra et al.  studied rapid eye movements (saccades), as these place the greatest demands on brainstem and cerebellar circuits controlling gaze. Thus, saccades are the rapid eye movements by which we shift our line of sight from one point to another. Although saccades are a sensitive test of brainstem and cerebellar function, they are still not routinely tested at the bedside. Instead of simply noting how fast the eyes could move, Serra et al.  focused on how they got there. Saccadic inaccuracy (dysmetria), requiring subsequent corrective movements, was a common finding in the patients. Such abnormalities in saccadic eye movements as prolonged latency and decreased peak velocity are believed to be indicative of brainstem or cerebellar lesions [4, 14, 15]. Farid et al.  reported that the most common saccadic abnormality is internuclear ophthalmoplegia. Other abnormalities in saccade testing included prolonged latency, inaccuracy, and decreased velocity in 4/25 (16%), 5/25 (20%), and 5/25 (20%) patients, respectively. Other investigators such as Noffsinger et al.  reported that 40% of their patients had such abnormalities. Similar results were also shown in other studies , .
Our study demonstrated a statistically significant difference between group I (study group) and group II (control group) as regards pursuit gain, which was lower in group I (study group). We also found a statistically significant difference between group I (study group) and group II (control group) with respect to pursuit catch-up saccades, which was higher in group I (study group). Jozefowicz-Korczynska and Pajor  reported VNG recordings of smooth pursuit tests with 0.3, 0.4, 0.5, and 1.5 Hz amplitude, and gain calculations were performed. On clinical bedside examination, disorders of smooth pursuit were found in 25% and with VNG in 76.6% of patients. In the MS patients the mean gain for all frequencies was significantly lower compared with the control group. Abnormal results of smooth pursuit tests were found in 61-80% of patients, which is similar to the results of Mastaglia et al.  ; Reulen et al., 1983;  . Gain decrease was a frequently recorded abnormality (Reulen et al. 1983) ,, . Thus, it was concluded that smooth pursuit examination provides a valuable parameter of brain dysfunction in MS patients. In a study by Farid et al.  smooth pursuit was symmetrically abnormal in the form of reduced gain in 16/25 (64%) patients, and this was by far the most common central finding in this study group. Four of them had abnormal pursuit pattern in the form of saccadic pursuit - that is, catch-up saccades.
Our study found a statistically significant difference between group I (study group) and group II (control group) as regards OKN gain, which was lower in group I (study group). To our knowledge there is only one paper on OKN abnormalities in MS that by Farid et al.  , who found OKN abnormality to be lower than that of the pursuit test in 14/25 patients (56%). This was not surprising, as the OKN test is less sensitive than the smooth pursuit test, presumably because OKN is the sum of the two tracking mechanisms namely, the smooth pursuit system and the saccadic system  .
EDSS is a measure of disability in MS. The correlation with the EDSS score in our study revealed that there was a statistically significant correlation between saccades and the EDSS score. Also a statistically significantly negative correlation was found between pursuit gain and EDSS score. In accordance with our study, Downey et al.  reported that patients with AEMs were associated with greater general disability. The Kurtzke EDSS scores in the AOM group (median 5.2) were significantly greater (P < 0.02) than the scores for the normal ocular motor (NOM) group. Also, Kurtzke FSS scores were greater in the AOM group for cerebellar functions (P < 0.03) and brainstem functions (P < nd brainstem functions (he AOM group for cerebellar functions (SS scores in the alities in multdifferent in the AOM and NOM groups. The previous study by Downey et al.  was confirmed by Derwenskus et al.  that this difference was sustained after 2 years in the follow-up study. AEM patients (17/40) remained significantly (P < 0.001) more disabled (median EDSS of 7.0) than those with normal eye movements (median EDSS of 5.0). Thus, the median EDSS of patients with normal eye movements (NEMs) (5.0) corresponded to being able to walk without aid for about 200 m, whereas the median EDSS of AEM patients (7.0) corresponded to being essentially restricted to a wheel chair. Each of the four patients who moved from the NEM group to the AEM group showed deterioration in their EDSS score (mean change: 2). Thus, it was concluded that the relationship between AEMs and disability in MS is a reproducible finding. Serra et al.  showed that patients with AEM signs during the bedside examination showed greater disability in the neurological evaluation on the EDSS scale compared with those with normal eye movements. They compared two groups of patients based on the results of bedside examinations (normal clinical vs. abnormal clinical group). For both groups, the greater the disability as per the EDSS score, the greater the decrease in the gain value in the VNG recordings.
Jozefowicz-Korczynska and Pajor  reported a correlation between gain values and EDSS score in MS patients. Therefore, they think that correlation of the EDSS score with the total number of abnormal tests in VNG is due to more frequent involvement of the vestibular structures. Surprisingly, the correlation was significant and greater for patients without evident abnormalities in clinical examination. As a consequence, the study of eye movements may be useful in demonstrating neurological dysfunction attributable to lesions that are clinically silent. In the study by Degirmenci et al.  the mean EDSS score of the patients was 1.77 (their population consisted of young and nondisabled patients who were in the early stages of the disease, similar to our study). They reported that VNG results concerning vestibular system involvement were still statistically significant both in symptomatic and asymptomatic patients. This result suggests that VNG is a helpful tool for the diagnosis of MS patients in the early stages of the disease by showing subsystem involvement. Correlation of the total number of abnormal tests in VNG with the EDSS score was statistically significant in the study. This result suggests that sensitivity of VNG does not depend on most of the clinical features if it is performed in detail.
Gaze-evoked nystagmus reflects impairment of the gaze-holding mechanism. The critical structures for gaze holding are located in the brainstem and the cerebellar flocculus, which is involved in controlling the optimum function of the brainstem integrators  . Besides a brainstem lesion, gaze-evoked nystagmus may also reflect cerebellar dysfunction, such as suggested by its frequent association with cerebellar-type AEMs that is, macrosquare waves, saccadic hypermetria, or impaired slow eye movements. In our study seven patients (12.96%) had gaze-evoked nystagmus and four patients (7.41%) had acquired pendular nystagmus. 1-Jozefowicz-Korczynska and Pajor reported that patients showed the followings: gaze-evoked nystagmus (r = 0.38, P < .30), abnormal clinical smooth pursuit test (r = 0.27. P < .27), and internuclear opthalmoplegia (r = 0.3. P < .3) in their study  (pursuit test (ystagmus (nskaM, PajorAM. Evaluation of the smooth pursuit tests in et al.  . They reported in their study the presence of five patients with pendular nystagmus with normal afferent visual pathway function. This could be explained by abnormal feedback loops that could be involving the oculomotor neural integrator, which normally guarantees stable gaze through mathematical integration of preoculomotor signals  . This idea is mainly supported by the saccadic resetting of the nystagmus and by the predominant location of lesions in the pontine tegmentum that could include cell groups of the paramedian tract involved in the oculomotor neural integrator feedback loops  .
We reported in this study a strong correlation between infratentorial brain volume (cerebellar and brainstem) and AOM eye movements. Degirmenci et al.  reported that most of their patients had vestibular symptoms. Pathologic neurological examination findings were found in only 60-70% of them and infratentorial MRI lesions were found in only 60% of them. In addition, VNG findings showing brainstem and/or cerebellum involvement were found in 100% of their patients with normal neurological examination findings and without brainstem and cerebellar lesions in MRI. This condition suggests that evaluation of vestibular symptoms with VNG is more sensitive than clinical examination and MRI. A study showed that VNG is significantly associated with brainstem and/or cerebellar involvement in RRMS and it was reported that 49% of asymptomatic lesions and 84% of symptomatic lesions can be detected by VNG (Sanders et al., 1985a  ; 1986  ). Downey et al.  reported that MRI showed abnormal signals in brainstem or cerebellum in 59% of patients with AOM scores and in 27% of patients with NOM scores. The MRI scans supported the notion that posterior fossa abnormalities were more common in patients with AEMs; this is consistent with prior volumetric MRI studies that measured brainstem and cerebellar functions  .
Derwenskus et al.  in a follow-up study to that by Downey et al.  reported that AEM and greater disability were associated with abnormal MRI signals in the brainstem or cerebellum, where disease may involve control circuits for eye movements as well as descending motor pathways. MRI scans showed abnormal signals in the brain stem or cerebellum of 60% of patients with AEMs and in 28% of patients with normal eye movements. We reported no statistically significant difference in oculomotor abnormalities between patients with brainstem lesions versus those with cerebellar lesions, which has not been compared yet in any other paper. Further studies are needed to address this issue. No statistically significant difference was found in oculomotor abnormalities between patients treated with solumedrol alone and patients having another add-on prophylactic drug. More data are required to compare our results.
| Conclusion|| |
Oculor motor system tests are more sensitive than conventional clinical examinations in identifying abnormalities in MS as compared with the control group. A significant difference was found between the study group and control group as regards saccadic latency, velocity, and accuracy. The smooth pursuit system showed significant difference regarding its gain and number of catch-up saccades. The optokinetic tracking system showed a significant difference in its gain. A significant correlation was found between MS severity as measured by EDSS and all three parameters of the ocular motor systems (saccades, smooth pursuit, and optokinetic tracking). Brainstem and cerebellar MRI lesions showed more significant abnormalities in the ocular motor systems. Gaze-evoked nystagmus and pendular nystagmus showed more significant abnormalities in the ocular motor systems.
When comparing different treatments, solumedrol alone as compared with solumedrol with other forms of prophylaxis resulted in no significant difference in ocular motor abnormalities. Cerebellar versus brainstem MRI lesions showed no significant difference in ocular motor abnormalities.
Ocular motor tests are sensitive and give much more information about the brainstem and cerebellar function by focusing on the dynamic aspects of eye movements. They should be included in assessment of cases of multiple sclerosis by developing a more detailed scale. One should consider the fact that the ocular motor examination is not part of the standard Kurtzke FSS scores of brainstem or cerebellar function. Ocular motor tests should be included as follow-up tests in cases of multiple sclerosis for disease progression, activity, and for determining the effectiveness of treatments.
Ocular motor tests should be performed in association with MRI (which may fail to show very small MS plaques in the brainstem and cerebellum) to complete functional assessment of multiple sclerosis by demonstrating the involvement of various subsystems and provide paraclinical evidence in MS diagnosis.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Van Stern GP. Supranuclear motility. Neuro-opthamaology 2009; 15
Trillenberg P, Heide W. Ocular motor testing techniques and interpretation. Eggers SDZ, Zee DS. Handbook of Clinical Neurophysiology
. 2010. Germany: Elsevier B.V. 2010; 88-100.
Zeigelboim BS, Arruda WO, Mangabeira-Albernaz PL, Iório MC, Jurkiewicz AL, Martins-Bassetto J, Klagenberg KF. Vestibular findings in relapsing, remitting multiple sclerosis: a study of thirty patients. Int Tinnitus J 2008; 14
Grénman R. Involvement of the audiovestibular system in multiple sclerosis. An otoneurologic and audiologic study. Acta Otolaryngol Suppl 1985; 420
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al.
Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69
Barkhof F, Filippi M, Miller DH, et al.
Comparison of MR imaging criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120
Tintoré M, Rovira A, Martínez MJ, Rio J, Díaz-Villoslada P, Brieva L, et al
.Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 2000; 21
Bagnato F, Jeffries N, Richert ND, Stone RD, Ohayon JM, McFarland HF, Frank JA Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 2003; 126
(Pt 8): 1782-1789.
Bitsch A, Kuhlmann T, Stadelmann C, Lassmann H, Lucchinetti C, Brück W. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann Neurol 2001; 49
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33
Jacobson GP, Newman CW, Kartush JM. Handbook of balance function testing
. San Diego: Singular Publishing Group; 1997.
Downey DL, Stahl JS, Bhidayasiri R, Derwenskus J, Adams NL, Ruff RL, Leigh RJ Saccadic and vestibular abnormalities in multiple sclerosis: sensitive clinical signs of brainstem and cerebellar involvement. Ann N Y Acad Sci 2002; 956
Serra A, Derwenskus J, Downey DL, Leigh RJ. Role of eye movement examination and subjective visual vertical in clinical evaluation of multiple sclerosis. J Neurol 2003; 250
Shepard N, Telian S, Smith-Wheelock M, Raj A. Balance disorders in multiple sclerosis; assessment and rehabilitation. Semin Hear.1990; 11
Williams NP, Roland PS, Yellin W. Vestibular evaluation in patients with early multiple sclerosis. Am J Otol 1997; 18
Farid AS, Shabana MI, Hosni HS, Thabet EM. Assessment of the vestibular function in patients with multiple sclerosis. Egypt J Neurol Psychiat Neurosurg 2004; 41
Noffsinger D, Olsen WO, Carhart R, Hart CW, Sahgal V. Auditory and vestibular aberrations in multiple sclerosis. Acta Otolaryngol Suppl 1972; 303
Jozefowicz-Korczynska M, Pajor AM. Evaluation of the smooth pursuit tests in multiple sclerosis patients. J Neurol 2011; 258
Mastaglia FL, Black JL, Collins DW. Quantitative studies of saccadic and pursuit eye movements in multiple sclerosis. Brain 1979; 102
Meienberg O, Müri R, Rabineau PA. Clinical and oculographic examinations of saccadic eye movements in the diagnosis of multiple sclerosis. Arch Neurol 1986; 43
Frohman EM, Frohman TC, Zee DS, McColl R, Galetta S. The neuro-ophthalmology of multiple sclerosis. Lancet Neurol 2005; 4
Leigh RJ, Zee DS. The neurology of eye movements
. 3rd ed. New York: Oxford University Press; 1999.
Sharpe J, Morrow M. Smooth pursuit disorders. In: Barber HO, Sharpe JA, editors Physiological and anatomical consideration. Vestibular disorders
. Chicago: Year Book Medical Publishers Inc.; 1988. 129-158
Hain T. Interpretation and usefulness of ocular motility testing. In: Jacobson G, Newman C, Kartush J, editors. Handbook of balance function testing
. Chapter 6. San Diego. London: Singular Publishing Group; 1993:101-122.
Derwenskus J, Rucker JC, Serra A, Stahl JS, Downey DL, Adams NL, Leigh RJ. Abnormal eye movements predict disability in MS: two-year follow-up. Ann N Y Acad Sci 2005; 1039
Degirmenci E, Bir LS, Ardic FN. Clinical and electronystagmographical evaluation of vestibular symptoms in relapsing remitting multiple sclerosis. Neurol Res 2010; 32
Leigh RJ, Zee DS. The Neurology of eye movements (contemporary neurology series)
. 4th ed. New York, NY: Oxford University Press; 2006.
Tilikete C, Jasse L, Vukusic S, Durand-Dubief F, Vardanian C, Pélisson D, Vighetto A. Persistent ocular motor manifestations and related visual consequences in multiple sclerosis. Ann N Y Acad Sci 2011; 1233
Das VE, Oruganti P, Kramer PD, Leigh RJ. Experimental tests of a neural-network model for ocular oscillations caused by disease of central myelin. Exp Brain Res 2000; 133
Averbuch-Heller L, Zivotofsky AZ, Das VE, DiScenna AO, Leigh RJ. Investigations of the pathogenesis of acquired pendular nystagmus. Brain 1995; 118 (Pt 2)
Edwards SG, Gong QY, Liu C, Zvartau ME, Jaspan T, Roberts N, Blumhardt LD. Infratentorial atrophy on magnetic resonance imaging and disability in multiple sclerosis. Brain 1999; 122 (Pt 2)
Reulen JPH, Sanders EACM, Hogenhuis LAH. Eye movement disorders in multiple sclerosis and optic neuritis. Brain 1983; 106:121-140.
Sanders EA, Reulen JP, Hogenhuis LA, van der Velde EA. Brainstem involvement in multiple sclerosis: a clinical and electrophysiological study. Acta Neurol Scand 1985a; 71:54-.
Sanders EA, Reulen JP, Van der Velde EA, Hogenhuis LA. The diagnosis of multiple sclerosis: Contribution of non-clinical tests. J Neurol Sci 1986; 72:273-285.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]