BRAINSTEM AUDITORY EVOKED POTENTIALS FINDINGS IN ANKYLOSING SPONDYLITIS

Background. Ankylosing spondylitis (AS) is a chronic infl ammatory potentially debilitating disease predominantly affecting the axial skeleton. A few intermittently published studies and research have proved the existence of some not yet explained neurophysiologic abnormalities in patients with AS. Objectives. The aim of this study was to investigate the brainstem auditory evoked potentials and its relation with clinical fi ndings, laboratory tests and pharmacological therapy used in patients with AS. Material and method. Thirty-nine patients with AS were included in the study. The control group was composed of 50 healthy subjects. BAEP were recorded for all subjects. Patients were assessed by clinical specifi c tests, infl ammatory laboratory tests, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and type of pharmacological therapy. Results. The results have shown differences between the control group and the patients with AS in most of the wave latencies. Correlations Schober test, Ott index, chest expansion measurement and BASDAI were signifi cant for some waves. CRP seems to be more valuable than ESR as a possible marker for neurologic subclinical involvement. Axial AS is more likely to be associated with BAEP abnormalities. There were also differences between the group with TNF alpha blockers therapy comparative with the group with other therapies. Conclusions. This study highlights some abnormalities of BAEP in patients with AS. Diagnosis of multiple sclerosis or demyelination due to administration of TNF alpha blockers should be excluded in medical practice. Collaboration between neurologists and rheumatologists should be considered in monitoring AS patients.


INTRODUCTION
Ankylosing spondylitis (AS) is a chronic infl ammatory potentially debilitating disease predominantly affecting the axial skeleton. Progression towards irreversible ankylosis due to vertebral fusion causes severe functional disability, with important impact on quality of life. Peripheral joints arthritis and other extra-articular organs such as the skin, eyes, pulmonar, cardiovascular and neurologic system are less frequently involved. The disease affects mostly HLA-B27-positive population, especially the male gender. The onset is usually in the second or third decade of life. (1)(2)(3) Most common neurological complications associated with AS are C1-C2 subluxation, spinal stenosis in the cervical or lumbar regions, cauda equina syndrome and radiculopathy. AS patients in latest stages of disease have an increased risk for spinal fractures with minor trauma due to association of osteoporosis and vertebral fusion progression leading to a long bony column. (1,4,5)

AIM AND OBJECTIVES
A few intermittently published studies and research have proved the existence of some not yet explained neurophysiologic abnormalities in patients with AS. Somatosensory evoked potentials, auditory evoked potentials, visual evoked potentials and magnetic motor evoked potentials abnormalities have been reported. (6-9) Furthermore, sporadic associations of AS and multiple sclerosis was also reported. (10-15) Neurologic complications largely due to demyelination mechanisms may be present in AS patients treated with TNF alpha blockers. (16)(17)(18)(19)(20)(21)(22)(23)(24)(25) The aim of this study was to investigate the brainstem auditory evoked potentials (BAEP) and its relation with clinical fi ndings, laboratory tests and pharmacological therapy used in patients with AS.

MATERIAL AND METHOD
Thirty-nine patients with AS were included in the study. The control group was composed of 50 healthy medication-free adults. All patients have been assessed in Rheumatology Department and BAEP were recorded in Neurology Department, both in Clinical Rehabilitation Hospital Of Iasi, Romania. This study has been approved by the institutional review board. Prior to study inclusion, the informed consent was signed by all subjects from both groups.
BAEP were performed with Nihon Kohden Neuropack for all patients and for all voluntaries in the control group. We used 80 dB HL alternating polarity clicks in each ear at a rate of 10/s and a masking white noise of 40 dB was used for the unstimulated ear. The electrodes were placed as following: ground electrode in the midline frontal area, the reference electrode at vertex and the active electrodes (A1, A2) at the ear lobes. We recorded the latencies of all the waves: I, II, III, IV and V for and the Interval Latencies (IL): I-III, III-V and I-V. Patients were assessed by clinical specifi c tests such as Schober test, Ott index, chest expansion measurement, infl ammatory laboratory tests: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), indexes: Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Anky-losing Spondylitis Disease Activity Index (BAS-DAI) and type of pharmacological therapy. The diagnosis of AS was made according to the modifi ed New York criteria. (26) All these parameters have been processed using the Statistical Package for Social Sciences (SPSS), version 16.0 for Windows. For the correlation test, p value of <0.05 was considered statistically signifi cant.

RESULTS AND DISCUSSIONS
The mean age of all the 39 patients, 26 males and 13 females, included in this study, was 40.65±14.34 years and the mean duration of disease of the patients was 13.31 ± 7.52 years.
BASDAI had a mean of 3,4 ± 2.3 and BASFI was 4.1±1,3. Most of the patients (n=25) were taking Nonsteroidal anti-infl ammatory drugs (NSAID) or sulfasalazine (SSZ) or the association between these drugs. Fourteen patients were treated with TNF-alpha blockers. BAEP results for all SA patients included in the study may be seen in Table 1. BAEP results for all the control group seen in Table 2. The left wave V latency in control group and in patients group had a signifi cant mean difference (0.19) p < 0.05 and CI 95%. We have also found signifi cant differences in values of I-III left interval (p < 0.05, CI 95%). For the I-V interval there was a mean difference of 0.29 which was very signifi cant for p < 0.001 and F > F0.001, CI 95%. The left wave I latency was in a signifi cantly correlation (p < 0.005, CI = 95%) with the duration of the disease, R = 0.286 (28%), CRP p < 0.05, Cl 95%, R = 0.458 (45%) and BASDAI, p < 0.05, Cl 95% and R = 0.525 (52%). ANOVA test showed the wave I latency was in a signifi cantly correlation with BASFI (p < 0.05, C.I. 95%). A positive and intermediate correlation between both left and right wave I latencies and the type of disease (axial or peripheral), r = 0.385 (38%) and 0.347 (34%) was signifi cant, p < 0.05. Pearson correlation between variables wave I latency and Ott index highlights that there is a negative and signifi cant correlation (p < 0.05) where r = -0.278 (27%). The disease duration wave one has r = 0.238 stg (23%) but insignifi cant which means that this variable can infl uence wave 1 but in combination with other factors. There was also a correlation between CRP and right wave I latency. Since regression line is oriented from the bottom up, with the points focused on the right, we can conclude that between the right wave I and CRP there is a close and positive correlation as seen in Fig. 1.
Right wave I latency is positively and intermediate correlated with CRP, r = 0.302 (30%), significant for p < 0.05. Also age is positively correlated , intermediate to intense and very signifi cantly, with disease duration, r = 0.587 (58%). Age was also correlated with Schober index, r = -0.536 (53%), and chest expansion measurement, r = -0.622 (62%). Left wave II latency is signifi cant correlated with disease duration, Ott index, ESR, BASDAI and chest expansion measurement, p < 0.05 and CI 95%. Left wave IV latency is negatively signifi cant correlated with Schober test and Ott index. Both left and wright IV waves are positively correlated with type of disease. Right wave V latency is correlated with CRP and type of disease.
There were differences of the latencies in the group of SA patients treated with TNF alpha blockers compared with the group with AINS/DMARDs. Results of BAEP in group treated with TNF alpha blockers and the group with other pharmacological treatment may be seen in Table 3 and Table 4.

CONCLUSIONS
This study highlights some abnormalities of BAEP in patients with AS. The results have shown differences between the control group and the patients with AS in most of the wave latencies. Correlations Schober test, Ott index, chest expansion measurement and BASDAI were signifi cant for some waves. CRP seems to be more valuable than ESR as a possible marker for neurologic subclinical involvement. Axial AS is more likely to be associated with BAEP abnormalities. There were differences of the latencies in the group of SA patients treated with TNF alpha blockers compared with the group with AINS/DMARDs. Multiple sclerosis or demyelination due to administration of TNF alpha blockers should be excluded in medical practice. Collaboration between neurologists and rheumatologists should be considered in monitoring AS patients.