© Borgis - New Medicine 1/2007, s. 2-5
*Jarosław Wysocki1, 2, Piotr Orszulak1
Analysis of key agents influencing therapeutic success in balance disturbances treated ambulatory by Betahistine
1Clinic of Otolaryngology and Rehabilitation II Medical Faculty University Medical School in Warsaw, Poland
Head of Clinic: Jarosław Wysocki, MD, PhD
2Institute of Physiology and Pathology of Hearing, Warsaw, Poland
Summary
Summary
Vertigo and dizziness are common medical problems, associated with several specialties. Management with these patients is lingering, difficult and not in every case successful. In order to find and assess possible factors influencing final therapeutic success in therapy of vertigo and balance disorders a prospective, questionnaire study in primary care units was realized. Patients (4648), adults and adolescents, both gender, suffering from vertigo or other balance disturbances were included into the study. Results of Betahistine (Histimerck(r)) application during a 30-60 days period in doses 24 or 48 mg/day was analyzed. Withdrawal of vertigo or dizziness in physical examination were undertaken as a therapeutic success. Generally results of therapy were better in patients with diagnosis of vertigo labyrhintica and in younger than in older patients. Statistically significant positive influence on therapeutic success was proved not for summaric dose of Betahistine but for summaric time of therapy and therapy according to alternative model: the different dose in the following 30 days. Head injury in the past, cervical spine degenerative changes and VIII nerve diseases deteriorated chances of headache, waving and visual disorders release but only for patients with diagnose of vertigo centralis. In patients with vertigo labyrhintica hypertension significantly deteriorated final result in headache release. It was also proved negative influence of acoustic injury on vertigo release in all the patients. We could conclude that to the group which is anticipated as having worse therapeutic effects belong older patients and patients burdened with cervical spine degenerative changes, acoustic injury and head or cervical spine injuries in the past. Extending the time of therapy until 60 days provides considerable positive effect.
Introduction
Patients with vertigo, dizziness and other balance disorders more frequently suffer from metabolic disorders such as excess weight, hyperlipoproteinemia, intolerance of glucose, hyperinsulinemia, however arterial hypertension, degenerative changes in cervical spine, disorders of arterial flow are also common in these patients [1, 2, 3, 4, 5, 6, 7, 8].
Dizziness and other disorders of equilibrium are widespread in populations of industrialized countries, particularly in people that are more then 40 years old [9, 10, 11, 12, 13]. 80% of patients with vertigo suffer from significant drop in the life´s quality, which is caused by dysphoria, difficulties in everyday life and by continuous search for medical aid [12]. In majority of the equilibrium´s disorders, attempts to discern the concrete etiologic factor, fail. Thus diagnoses often state a vascular background or idiopathic origin, which makes a causal treatment impossible [5, 10, 14, 15]. Thorough study of etiopathogenesis of vertigo is difficult because epidemiological research provides very little detailed data [10, 12, 15, 16]. Fortunately very recently appeared some detailed epidemiological works on occurrence of different burdens in patients with vertigo. This works were stating that, for example, the occurrence of the diabetes is 2-3 times more often in patients with vertigo than in control groups [1, 2, 3, 4, 5, 6, 7]. Nevertheless the research lacks of data on the influence of these burdens on results of therapy.
The Betahistine is an effective medicine in the practical treatment of vertigo. It is a medicine of complex and not fully understood mechanism of work [17]. It is an analogue of histamine with large affinity to receptor H3 (the antagonist) and small affinity to receptor H1 [the agonist], exerting a final effect of vasodilatation in the area of vertebral and basilar arteries [18]. Its curing influence concerns not only vestibulocochlear organ but also the central nervous system. In patients with vertigo and after recent brain apoplexy a betahistine therapy can be an equivalent of traditional treatment with antithrombotic drugs or even better [19].
Materials and methods
Research was carried on patients with hearing and balance impairment, treated by otolaryngologists or neurologists with Histimerck(r) at outpatient wards. The analysis includes 4648 persons in age spectrum from 16 to 91 years old. Diagnoses stated Vertigo originis centralis (diagnosis I) or Vertigo labyrhintica (diagnosis II). The inquiry was specially constructed for the needs of this investigation. Patients answered a questionnaire on how they were experiencing their ailments during the three major periods: 1) before undertaking the treatment, 2) after 30 days of treatment and 3) after 60 days of therapy. Apart from questions on demographic data and ailment, inquiry contained also a string of questions referring to possible coincident factors causing deterioration, such as: the diabetes, arterial hypertension, noise exposure, intake of ototoxic medicines, old head injury, degenerative changes in cervical spine and/or its injury, pathologies in middle or internal ear, and diseases of vestibulo-cochlear nerve.
In therapy of vertigo betahistine (Histimerck(r)) was applied in periods of 30-60 days, in doses of 24 or 48 mg/day.
The data from questionnaires were saved on the computer using special, author´s coding program. These operations allowed to obtain a data with possibly little mistakes, which are additionally dividable in to homogeneous groups.
The descriptive statistics allowed to obtain basic data on a numbers of individual gatherings. Various statistical tests in analysis of differences and correlation were applied. T-Student test, analysis of variance and χ2 test showed differences in the matrix of the data. During statistical analysis calculated overage surpluses of Wanke were employed, which informed about excessive numbers in some classes of correlation matrix. The coefficients Pearson´s of correlation were counted characterising the strength of relationship among pairs of variables. It the value of level of significance α= 0,05 was accepted. Nevertheless in majority of cases this level was lower than 0,001 or even 0,0001, which says that proved differences can occur with very large probability.
Table 1. Distribution of gender and age in the study group regarding final diagnose.
| Diagnose/gender and age | Vertigo originis centralis | Vertigo labyrinthica |
| number | men | 1159 | 794 |
| women | 1631 | 1064 |
| mean age | men | 59.47 | 51.18 |
| women | 59.36 | 49.89 |
Represents a number of patients distinguished by sex and diagnosis into several groups. Age-dependant differences were statistically important. The patients with diagnosed Vertigo originis centralis were generally older than patients with diagnosed Vertigo labyrinthica.
Table 2. Percentage of patients, which presented the following symptoms regarding diagnose-distinguished groups.
| Diagnose/symptoms | Vertigo originis centralis | Vertigo labyrinthica |
| vertigo | 62.11 | 89.54 |
| sickness, vomiting | 44.54 | 65.81 |
| waving of ground | 69.25 | 38.49 |
| blurs before eyes | 54.27 | 25.64 |
| headache | 65.47 | 38.53 |
Shows the subjective symptoms reported by both kinds of patients during the first visit. All differences were statistically significant.
Table 3. Percentage of patients (in groups) burdened with individual factors.
| Factor | Vertigo originis centralis | Vertigo labyrinthica |
| noise exposure/acoustic injury | 14.34 | 20.43 |
| hypertension | 46.88 | 24.25 |
| diabetes | 12.69 | 5.58 |
| brain stroke | 13.63 | 3.22 |
| degeneration of cervical spine | 71.87 | 43.7 |
| labyrhintitis in the past | 5.33 | 12.7 |
| chronic otitis media present or in the past | 4.47 | 13.94 |
| diseases of VIII-th nerve in the past | 3.25 | 7.37 |
| therapy with aminoclycosides in the past | 7.71 | 11.86 |
| therapy with polypeptide antibiotics in the past | 2.13 | 3.23 |
| therapy with cytostatic drugs in the past | 1.11 | 1.44 |
| therapy with diuretic drugs in the past | 22.12 | 11.94 |
| middle ear operations in the past | 1.9 | 7.9 |
| other operations in total anesthesia in the past | 36.22 | 29.04 |
| head injury in the past | 16.13 | 13.21 |
| cervical spine injury in the past | 9.8 | 7.7 |
Presents the factors burdening patients in both groups. These factors could increase risk to more pronounced symptoms or an increase in their intensity. Only cytostatic treatment in the past did not hold any difference in either of patient diagnosis-groups. All other differences were essential or highly essential. For example, patients with diagnosis I more often suffered from arterial hypertension, and therefore more often ingested diuretics. Perhaps because of age average patients with diagnose I also more often (in over 70%) suffered from spondylosis of cervical spine. They also more frequently suffered from diabetes.
On the other hand, patients with diagnosis II more often worked in high noise level environment, had chronic otitis media or were more often exposed on ototoxic medicines such as aminoglycosides or polypeptides.
Detailed analysis regarding sex showed that some factors were significantly more often present in men. These were: noise exposure, chronic inflammation, operation on the middle ear, injury to the head or injury of the cervical spine.
Results
Generally results of therapy were better in patients with diagnosis of vertigo labyrhintica and in younger than in older patients. Statistically significant positive influence on therapeutic success was proved not for summaric dose of betahistine but for summaric time of therapy. Head injury in the past, cervical spine degenerative changes and VIII nerve diseases deteriorated chances of headache, waving and visual disorders release but only for patients with diagnose of vertigo centralis. In patients with vertigo labyrhintica hypertension significantly deteriorated final result in headache release. It also proved negative influence of acoustic injury on vertigo release in all the patients.
Table 4. Percentage of patients in which the symptoms withdrew after the control visit. The second visit examination results marked in grey.
| Percentage of treated on/diagnose | After first visit | After second visit |
| Vertigo originis centralis | Vertigo labyrinthica | Vertigo originis centralis | Vertigo labyrinthica |
| vertigo | 5.73 | 10.36 | 41.69 | 52.40 |
| sickness, vomiting | 30.69 | 38.99 | 69.86 | 73.54 |
| waving of ground | 7.49 | 13.35 | 38.79 | 47.51 |
| blurs before eyes | 12.57 | 25.37 | 44.43 | 56.76 |
| headache | 9.63 | 12.56 | 29.67 | 35.67 |
Presents the progress in treatment measured as a recession in symptoms that were mentioned by patient during the first visit. Continuation of the therapy after patients´ second visit led to statistically essential increase in successful recoveries, especially for curing the feeling of rotations. This results show that therapy prolonged to 60 days is important to treat Vertigo labyrhintica.
Table 5. Progresses in the treatment process according to diagnose and total drug dosage calculated as daily dosage x number of days of treatment (in gram).
| Progress in treatment/diagnose | Mean total drug dosage |
| Vertigo originis centralis | Vertigo labyrin-thica |
| vertigo | lack of relieve | 2.64 | 2.62 |
| relieve | 2.60 | 2.57 |
| total withdrawal | 2.57 | 2.61 |
| sickness, vomiting | lack of relieve | 2.61 | 2.70 |
| relieve | 2.67 | 2.56 |
| total withdrawal | 2.61 | 2.59 |
| waving of ground | lack of relieve | 2.68 | 2.61 |
| relieve | 2.62 | 2.53 |
| total withdrawal | 2.59 | 2.58 |
| blurs before eyes | lack of relieve | 2.63 | 2.63 |
| relieve | 2.62 | 2.55 |
| total withdrawal | 2.58 | 2.57 |
| headache | lack of relieve | 2.62 | 2.60 |
| relieve | 2.61 | 2.57 |
| total withdrawal | 2.59 | 2.56 |
Represents results of calculations of a total dosage of drug during therapy (the time of therapy x the dose). Among data contained in the table, an essential difference between groups created according to dose (the larger total dose versus the smaller total dose) exists in diagnosis II only with regard to the feeling of waving ground and in diagnosis I only in case of nauseas, the waving of ground and indistinctness of vision.
Discussion
Results of our investigations show that peripheral damages are connected mostly with the feeling of rotary motion, which rarely appears in central damages. Neuhauser et al. confirmed this theory [12]. Their epidemiological questionnaires, which were conducted on similarly numerous study group, show that interpreting the symptoms alone, it is possible to correctly diagnose disorders of vestibular character [diagnosis II] in about 90% of patients. Therefore the questionnaire on anamnesis is very reliable, specific, and sensitive [12].
The problem of specifying the optimum betahistine dose was not ultimately resolved. The majority of authors of analyzed works prescribed two basic doses: 3x8 or 3x16 mg or their modifications [19, 20, 21, 22]. Oosterveld applied the dose of the 3x12 mg in different types of peripheral disorders of equilibrium [23]. Petrova et al. [22] applied Betaserc to relatively young patients, getting similar therapeutic results to those in present work. They recommend to use the dose of 3x16 of mg, while in acute phase. Kaźmierczak [20] also affirms, that higher dose gives better results in treatment. Our observations disagree with that, as they show higher recovery percentage in patients, whose total dose was lower. The superiority of alternant therapy proved in present work is an interesting riddle and problem that requires confirmation further investigations.
Some researchers state varying effectiveness of betahistine in cases of vestibular and cochlear disorders with worst results in tinnitus and hearing impairment and best results in typical vertigo with nauseas and vomiting [21, 23]. Hoffer [2] states that the treatment is longest in disorders of equilibrium of spatial orientation character without typical vertigo and therefore of central disorders. It can be confirmed by our own observations. Better results of treatment in patients with diagnosis II are probably due to their younger age, as a correlation between age and therapy success was proved. Moreover Vertigo labyrhintica has tendencies to spontaneous withdrawal as a result of progressive central compensation.
The time of therapy usually takes several weeks [19, 21, 22, 23]. Only Kaźmierczak [20] applied therapy lasting for 180 days.
Patients with degenerative changes of cervical spine are numerous group of 42,3% of all vertigo patients. Moreover 70,1% of vertigo patients suffer from insufficient vasculature of basilar artery, which is a cause of labyrinth disorders in app. 50% of patients during their head movements [8]. About 52% patients suffering from attacks of vertigo showed pathologies of vertebral and basilar arteries as well as connected with this blood flow disorder [7]. Maybe this permanent anatomical changes cause that treatment in these cases gives worse effects.
Conclusions
1. To the group which is anticipated as having worse therapeutic effects belong older patients and patients burdened with cervical spine degenerative changes, acoustic injury and head or cervical spine injuries in the past.
2. Extending of time of therapy until 60 days provides considerable positive effect.
Piśmiennictwo
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