SOME ASPECTS OF BALANCE DISORDER IN PATIENTS WITH MULTIPLE SCLEROSIS Introduction Multiple sclerosis

Th e aim of this study was to analyze: frequency of balance disorder (vertigo and disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP) and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis (MS) patients with balance disorder, relation of patient’s disability status to balance disorder and relation of the changes in MRI of the brainstem to AEP abnormalities. It was analyzed  patients with relapsing-remitting form of MS. Two groups of patients were made consecutively under Expanded Disability Status Scale score (EDSS): A (EDSS ≤,) and B (EDSS ≥,). Th e study was retrospective-prospective. After the neurological exam AEP and MRI of the brain have been done. Balance disorder has been verifi ed as initial symptom in  (,) and out of them disequilibrium experienced  (,) patients. During the relapses balance disorder experienced  () patients and in  (,) it was disequilibrium. Among them  (,) were with lower EDSS (≤,) and  (,) with higher EDSS score (≥). Th ere is no correlation between disability status and vertigo which means that vertigo is not more frequent in more disabled patients and vice-versa. Th e AEP were pathological in  () patients. Of all  patients with vertigo AEP were pathological in  (,) while in  patients without vertigo pathological AEP were in  (,) but it is not statistical signifi cant. Th e most frequent characteristic of AEP changes were prolonged inter-peak latency III-V waves ( patients or ). Th e plaque in brainstem visualized by MRI was found in  (,) of patients ( or , of them had pathological AEP and in three patients AEP were normal). In group of patients with pathological AEP,  (,) of them had plaque in brainstem. In other three patients with normal AEP it was visualized plaque in brainstem. In the group of  patients with balance disorder,  (,) had plaque in brainstem as well as  (,) out of  patients without balance disorder had plaque in the brainstem. Th is diff erence is not statistical signifi cant. It is concluded that the vertigo (including disequilibrium) is relatively often (,) initial symptom of MS. Vertigo is not more frequent in patients with higher EDSS score and vice-versa. Pathological AEP are frequent neurophysiologic fi nding in both () patients with (,) and without (,) vertigo. Th e most often pathological characteristic of AEP are prolonged interpeak latency of III-V waves (,), as well as abnormalities of V and than IV wave. MS plaques in brainstem visualized by MRI technique are frequent in both groups of patients with and without pathological fi nd-


Introduction
Multiple sclerosis (MS) is chronic, inflammatory immune disease of central nervous system characterized by destruction of myelin sheaths, axonal damage and oligodendrocites degeneration in various parts of the brain and medulla.Among the most common symptoms (optic neuritis, ophtalmoplegia, paresis and paralysis, sensory disturbances, ataxia, bladder and bowel disorder), balance disorder (disequilibrium and vertigo) could be the symptom as well.Vertigo is not a disease.Th e term vertigo refers to the sensation of spinning or whirling that occurs as a result of a disturbance in balance (equilibrium).The sensation of movement is called subjective vertigo and the perception of movement in surrounding objects is called objective vertigo.Some other feelings of dizziness, lightheadedness, faintness, and unsteadiness are named: disequilibrium i.e. pseudovertigo ().Therefore, for complete evaluation, diagnose and treatment it is very important to insist and realize what exactly term vertigo does mean for patients and how do they describe it.

Patients and Methods
In retrospective -prospective study it was analyzed  patients with relapsing -remitting multiple sclerosis (RRMS).It was evaluated: the frequency of vertigo as initial symptom and during the course of disease; auditory evoked potentials (AEP); magnetic resonance imaging (MRI) of the brain; disability status and balance disorder.Disability status was defi ned by Expanded Disability Status Scale-score (EDSS) ().Consecutively, the patients have been divided in two groups: A (EDSS ≤,); B (EDSS ≥,).MRI of the brain were focused on plaques in brainstem, cerebellum and both in brainstem/cerebellum. AEP exam have been done by standard protocol in Evoked potential laboratory, Department of neurology Tuzla.In the analysis, standard statistical tests have been used: mean value and standard deviation, T test, X  -test.Diff erences p<, were considered signifi cant.

Results
Of all patients it was (,) female and  (,) male.Average age of all patients was ,±, (male: ,±,, female: ,±,).In group A (EDSS ≤ ,) were  patients () and in group B (EDSS ≥ ,)  ().Average EDSS in group A was ,±,, in group B was ,±,.Balance disorder experienced  (,) patients.Out of this  () patients were in group A (EDSS ≤ ,), and  (,) in group B (EDSS ≥ ,) (p>,)(Figure ).For all patients disequilibrium as initial and symptom during the relapse, was more frequent in both groups, but it was not signifi cant neither as initial symptom (vertigo: p=,; disequilibrium p=,) nor during the relapse (vertigo: p=,; disequilibrium: p=,) in both separately analyzed groups (Figure ).Initially, vertigo was in  (,) patients: group A  (,), group B  (,).Otherwise, disequilibrium as initial symptom was in  () patients; group A  (), group B  (,).During the relapse, out of  () patients, vertigo had  (,) patients: group A  (), group B  (,); disequilibrium experienced  (,) patients: group A  (,), group B  (,).In group A, as initial symptom, disequilibrium was more frequent ( or ,) in order to vertigo ( or ,).It was the same in group B (disequilibrium  or ; vertigo  or ,), but there was no statistical signifi cance (Figure ).AEPs was pathological in  () patients: group A  (,), group B  ().Twenty-eight patients (,) out of  with balance disorder from both groups had pathological AEP; otherwise,  (,) patients out of  with no balance disorder had same AEP fi nding.In group A (patients with no balance disorder) abnormal AEP was in  (,) out of .In the same group (patients with balance disorder) it was abnormal in  patients (,) (p=,).In group B  (,) patients with balance disorder had pathological AEPs, as well as  (,) patients with no balance disorder.No statistical signifi cance (p=,) (Table ).Th e characteristics of AEP fi ndings are shown in Figure .Th e most fre-quent AEP fi nding in group A was prolonged interpeak latency III-V waves, which was found in  (,) patients.Same result was in group B as well ( patients or ,).Th ere was no statistical signifi cance (p=,).Absence of the wave III was registered in  (,) patients of group A and  (,) in group B what was signifi cant (p=,).It was verifi ed no signifi cance in absence of waves IV and V in both groups.MRI of the brain and cervical spine has been done to all patients.In Figure  it was presented distribution of the plaques primarily being focused on plaques just in brainstem, than plaques just in cerebellum and both in brainstem and cerebellum.Patients with the plaques both in cerebellum and brainstem were separated group and were not included in group of patients with plaques just in cerebellum or just in brainstem.Most plaques have seen in brainstem.

Discussion
Vertigo as diagnostic problem is big challenge for many doctors of various specialties.Experiences in balance disorders research pointed out that most usual was peripheral cause, so in such diseases like MS is, it is rare as the only sign of disease.Vertigo could be initial symptom of disease in approximately  of cases ().Paty () also found that vertigo could be initial symptom and could be indicator for benign long term course of MS.   3. Distribution of auditory evoked potentials fi ndings and plaques in brainstem in both groups A and B in order to balance disorder and this must not be avoided in patient's follow ups ().Among  MS patients,  could be clinically evaluated during one vertigo episode;  () experienced benign paroxysmal vertigo, and  () had relapse with lesions in brainstem ().Rae-Grant et al. () in their study found that  of MS patients during relapses experienced disequilibrium.Results of this study are somewhat diff erent than results in published analyses.Similar as in collected studies, vertigo as one kind of balance disorder and as initial symptom was not so often, although more frequent than results in these studies.In the current study, more often is disequilibrium during the relapse.Diff erences could be explained with possible new plaques during the relapse, primarily located in brainstem than in cerebellum as well.Also, it should not be avoided personal patients and their family's attitude to disease.In diagnostic protocols AEP fi nding is one of neurophysiologic methods and could be positive in - of patients even with no symptoms and could lead to diagnose of MS ().With various approaches there have been done many AEP studies.).In current study there are more pathological AEP then in collected articles.Th e explanation for this could be the fact that majority of patients had balance disorder during the relapses.Concerning the characteristics of pathological AEP, most frequent is prolonged interpeak latency I-V waves as well as abnormalities and/or absence of the wave V.In group with more disabled patients most frequent is absence of the wave III.Analyzes Robinson () and Dabić-Jeftić () pointed out abnormalities in wave V but they did not do evaluation of AEP in order to disability status.With MRI done, defi nitive diagnose of MS become very reliable.Plaques could be visualized in any part of the brain and spinal cord, but most frequent in ventricular regions, supracalosal, and in  could be seen in brainstem ().Grenmann et al. () concluded that balance disorder could be related to MRI fi nding.Th ey have been focused on plaques verification in brainstem and cerebellum.Th e results we had in our study correlate with previously published results.

Conclusion
Vertigo was found in , of MS patients.As initial symptom disequilibrium is statistically more frequent () than vertigo (,).Changes in fi nding of auditory evoked potentials was found in  of MS patients, more in patients with vertigo (,) than with no vertigo (,).Concerning magnetic resonance imaging of the brain, demyelination (plaques) in brainstem was seen in  of MS patients,  in cerebellum, and both in cerebellum and brainstem in ,.Vertigo experiences MS patients with various disability statuses.Patients with higher score do not have more prominent vertigo in order to patients with lower score of disability.In patients with higher score of disability, changes are in all region of brainstem what are diff erent to patients with lower score.Mostly, changes in these patients are in upper parts of brainstem.Th ere is no statistical signifi cance in frequency of abnormal AEP and plaques in brainstem of MS patients.MS patients could have visualized by MRI of the brain plaque in brainstem as well as normal AEP and vice-versa.
Otherwise, Frohman et al.(), published study that "real" vertigo could be verifi ed in  of MS patients.According to this study, demyelination in vestibular nuclei generates vertigo in patients.During the course of disease majority of MS patients could have disequilibrium.Episodes of central (as opposed to peripheral) vertigo are not uncommon.Th e nystagmus accompanying central vertigo has a rapid onset, does not fatigue easily, and changes with direction of gaze.Vertigo usually is accompanied by other complaints that can be directly attributed to brainstem or cerebellar pathway involvement (eg., diplopia, dysarthria) ().Alpini et al.()  published that balance disorder due to changes in brainstem and cerebellum is common in MS patients although this disorder could be of peripheral origin, like positional paroxysmal benign vertigo.Also, in study done by Paty (), more than  of MS patients have intermittent episodes of vertigo.Many years before defi nitive diagnose of MS, vertigo could be isolated symptom

TABLE 1 .
Auditory evoked potentials in multiple sclerosis patients with and without balance disorder in both groups BS -Brainstem, C -Cerebellum, BSC -Brainstem and cerebellum, BD -balance disorder, NBD -no balance disorder; *p<0,05 TABLE 2. Distribution of patients in both groups in order to balance disorder and localization of the plaquesFound plaques in brainstem were in  (,) patients of group A and  (,) of group B what is signifi cant for group A (p=,).Plaque in cerebellum (group A) was in  patients (,); in group B in  (,) what is signifi cant for group B (p=,) as well as plaques in cerebellum/brainstem (p=,):  (,) patients.Plaque in brainstem and/or cerebellum, of all analyzed patients (N=), was in  (,):  (,) in group A  (,) and  (,) in group B. In group A,  (,) out of  patients had balance disorder and in group B,  (,) out of  patients experienced the same.In table  are presented patients in both groups A and B with balance disorder associated with plaques just in brainstem, cerebellum as well as in both brainstem/ cerebellum.Plaque in group A had more patients with no balance disorder( or ,), what is not signifi cant.Otherwise, it is signifi cant in patients' group A with balance disorder and registered plaques both in brainstem and cerebellum in order to patients in group B ( or  patients) (p<,).In group B most frequent localization of the plaque both in brainstem and cerebellum is in patients with no balance disorder ( or ,), but it is not signifi cant.Also, it was not signifi cant verifi ed plaques in brainstem or cerebellum with balance disorder in patients' group B. In group A pathological AEP fi nding Kitanoski et al. ()analyzed AEP fi ndings in  MS patients and  were abnormal.Otherwise, Bruner et al.()did not have any abnormal AEP fi nding although  patients out of  who had clear eight cranial nerve aff ection.Robinson and Rudge () evaluated  patients with various different neurological diseases (MS, Arnold -Chiari malformation, intracranial tumors, vascular lesions in brainstem) and found signifi cant correlation between brainstem dysfunction and pathological AEP in MS patients.Japaridze et al.()in their analysis had abnormal AEP in  of patients with MS.According to one evaluation done in our EP lab., this percentage was ,