Multimodal treatment of persistent postural–perceptual dizziness

Abstract Background Persistent postural–perceptual dizziness (PPPD) is a chronic disorder with fluctuating symptoms of dizziness, unsteadiness, or vertigo for at least three months. Its pathophysiological mechanisms give theoretical support for the use of multimodal treatment. However, there are different therapeutic programs and principles available, and their clinical effectiveness remains elusive. Methods A database of patients who participated in a day care multimodal treatment program was analyzed regarding the therapeutic effects on PPPD. Vertigo Severity Scale (VSS) and Hospital Anxiety and Depression Scale (HADS) were assessed before and 6 months after therapy. Results Of a total of 657 patients treated with a tertiary care multimodal treatment program, 46.4% met the criteria for PPPD. PPPD patients were younger than patients with somatic diagnoses and complained more distress due to dizziness. 63.6% completed the follow‐up questionnaire. All patients showed significant changes in VSS and HADS anxiety, but the PPPD patients generally showed a tendency to improve more than the patients with somatic diagnoses. The change in the autonomic–anxiety subscore of VSS only reached statistical significance when comparing PPPD with somatic diagnoses (p = .002). Conclusions Therapeutic principles comprise cognitive–behavioral therapy, vestibular rehabilitation exercises, and serotonergic medication. However, large‐scale, randomized, controlled trials are still missing. Follow‐up observations after multimodal interdisciplinary therapy reveal an improvement in symptoms in most patients with chronic dizziness. The study was not designed to detect diagnosis‐specific effects, but patients with PPPD and patients with other vestibular disorders benefit from multimodal therapies.


| INTRODUC TI ON
Functional comorbidity is very common in patients with chronic dizziness (Staibano et al., 2019). Approximately 30%-50% of persistent dizziness cannot be fully explained by an identifiable medical illness (Schmid et al., 2011), and these patients mostly do not reveal any pathological results in technical diagnostics. Moreover, chronic dizziness and vertigo often are related to anxiety and depression, as well as to cognitive impairments (Lahmann et al., 2015).
In 2017, consensus criteria for persistent postural-perceptual dizziness (PPPD) have been defined by an expert panel . PPPD is a functional disorder that causes significant distress or functional impairment. It is characterized by symptoms of fluctuating dizziness, unsteadiness, and nonspinning vertigo on most days for at least three months . Upright posture, active, or passive motion without regard to direction or position, and exposure to moving visual stimuli or complex visual patterns may exaggerate symptoms. Mostly, the disorder is initially triggered by events that cause vertigo, unsteadiness, dizziness, or problems with balance. The symptoms cannot be better explained by another disease or disorder (Staab, 2020).
The definition of PPPD as a functional disorder is clearly separated from vestibular symptoms caused by a structural deficit of the vestibular system but also is distinctively separate from psychiatric causes . Functional disorders are considered as a change in the functioning of an organ unrelated to structural or cellular deficits (Dieterich & Staab, 2017). Consecutively, a change in functional connectivity in neuronal networks could recently be demonstrated in patients with PPPD (Li et al., 2020).
The principle of cognitive-behavioral therapy is based upon the premise that mental disorders and psychological distress are maintained by cognitive factors. Thus, CBT stimulates the patient to identify and to challenge the validity of maladaptive cognitions and therefore modify maladaptive behavioral patterns (Hofmann et al., 2012). CBT techniques applied in chronic dizziness comprise psychoeducation (information about dizziness), explanation and discussion of associations between assumptions (about dizziness), thoughts, moods and behaviors, behavioral experiments, exposure to feared stimuli, and attentional refocusing, coping strategies, and self-observations (Edelman et al., 2012;Schmid et al., 2011). In addition, patients learn relaxation techniques.
Generally, the studies show a small but clinically relevant effect of CBT concerning dizziness (Edelman et al., 2012;Limburg et al., 2019;Schmid et al., 2011). However, in a one-year follow-up of 20 patients with phobic postural vertigo no treatment effect remained after CBT (Holmberg et al., 2007). Vestibular rehabilitation (VR) is an exercise-based group of approaches to train the system to overcome dizziness, vertigo, and balance disturbances. VR has especially been shown to improve symptoms after unilateral vestibular loss (McDonnell & Hillier, 2015). VR exercises are based upon different physiotherapeutic approaches (Kundakci et al., 2018;McDonnell & Hillier, 2015). Compensation is the ability of the brain to learn and, therefore, to change the functioning of central nervous networks. Substitution is a process that stimulates the use of intact sensory inputs (e.g., visual or somatosensory) in contrast to dysfunctional inputs (e.g., in the case of vestibular loss). Adaptation means that errors in visual-vestibular and balance systems can be corrected and readjusted. Habituation means that the system may reduce its responsiveness to motion stimuli in order to reduce the symptoms of dizziness.
Physical exercises and training comprise postural control exercises and gate stabilization, conditioning activities and occupational retraining, coordination training, and exercises for gaze stabilization.
Recent studies (Nada et al., 2019;Thompson et al., 2015) found beneficial effects on patients with PPPD.
Selective serotonin reuptake inhibitors (SSRI) represent pharmacological options to modify anxiety and depression (Staab, 2016(Staab, , 2020. Existing studies in chronic dizziness and vertigo are all open-labeled and nonrandomized  but show some beneficial effects (Horii et al., 2007;Staab & Ruckenstein, 2005;Staab et al., 2004). Sertraline and fluvoxamine were the most often used substances. However, the evidence level is relatively low.
As all these therapeutic effects are significant but rather limited, the use of a combination of these therapeutic principles suggests itself. Therefore, the aim of this study was to evaluate the effects of an interdisciplinary multimodal therapy program we use in our tertiary care specialized center for dizziness and vertigo. Here, we analyzed a database of 657 patients with chronic dizziness who participated in our day care multimodal treatment program with a focus on patients who met the diagnosis criteria for PPPD.

| MATERIAL S AND ME THODS
We analyzed a database of patients with chronic dizziness who participated in a day care multimodal treatment program. The data were prospectively collected between June 2013 and March 2017 in the Center for Vertigo and Dizziness of Jena University Hospital. These data have already been analyzed to define age-related characteristics of patients with chronic dizziness (Dietzek et al., 2018). The study was approved by the local ethics committee (ethics committee of the Friedrich-Schiller-University Jena, number 5426-02/18).
Written informed consent for study participation was obtained from all patients.
Multimodal and interdisciplinary day care treatment took place from Monday to Friday with an average of 7 hr of therapy per day.
The therapeutic team consisted of a nurse, a neurologist, a psychologist, and a physiotherapist. The elements of the multimodal group therapy were specific physiotherapeutic training, CBT-based psychoeducation and group therapy, training of Jacobson's muscle relaxation technique, and health education. The group sizes varied between 8 and 10 patients. In addition, every patient had an individual session with the psychologist for psychological assessment and counseling and an individual session with the neurologist for medical evaluation and treatment optimization as well. Table 1 shows the time schedule of the therapy week. Every patient had an outpatient consultation with a neurologist including a thorough diagnostic process before the patient was subjected to the therapy week.
All patients filled out a questionnaire before therapy begun. Age, gender, and medical diagnoses were collected. The patients were contacted via mail to fill out a second questionnaire six months after attendance of the day care therapy program.
The Vertigo Severity Scale (VSS) was used as assessment tool to quantify vertigo and dizziness symptoms (Yardley et al., 1992). The VSS comprises two subscales: vestibular-balance (VSS-V) and autonomic-anxiety (VSS-A) (Kondo et al., 2015). The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression (Andersson, 1993). In addition, the intensity of vertigo/ dizziness and the distress due to vertigo/dizziness were quantified using a visual analog scale ranging from 0 to 10.
Statistics were performed using SPSS 21 (IBM Corp., IBM SPSS Statistics for Windows, Version 21.0.0). All data are reported as mean and standard deviation or as 95% confidence intervals. Paired and unpaired t tests were used appropriately for within-and between-group comparisons. Change in scores in follow-up assessments was represented as the difference between assessment scores before therapy and after 6 months follow-up. As a beneficial effect is represented by a decline in score over time, differences become positive if symptoms decrease. Generally, a two-sided significance level of p < .05% was assumed.

| RE SULTS
A total of 657 patients (mean age 57.5 years, standard deviation 15.2, 60% female, and 40% male) were analyzed. Figure Table 2 shows the baseline characteristics of both patient groups. PPPD patients were younger than patients with somatic diagnoses and complained more distress due to dizziness. They had statistically significant higher scores in VVS, VSS-A, and HADS anxiety.

| D ISCUSS I ON
A major advantage of the PPPD concept is that it is a priori not necessarily connected to a specified underlying psychological process, and may be present alone or coexist with other conditions. In addition, a multifactorial pathophysiological concept is conjoined to PPPD (Seemungal & Passamonti, 2018).
Suggested mechanisms of PPPD initiation and sustainment are mainly based upon a maladaptive and dysfunctional process affecting systems for balance control and vestibular processing . First of all, PPPD is triggered by an event of acute dizziness or vertigo, which could be not only a transient somatic dysfunction but also an acute psychological event such as a panic attack. A cycle of maladaptation  leads to a persistence of symptoms, although the triggering event may already be dissolved.
Predisposing factors may be originated in neurotic personality traits (Chiarella et al., 2016)  thoughts, fears, and anxious self-inspection are processes that may further sustain symptoms and lead to significant distress or functional impairment. The main goal of therapy is to discontinue this maladaptive cycle, and it is obvious that interventions with variable approaches may be suited to achieve this goal.
Therefore, treatment strategies of PPPD include patient education, vestibular rehabilitation, cognitive and behavioral therapies, and medication (Dieterich & Staab, 2017). Clinical studies analyzed different therapeutic principles (see Table 4  10 sessions CBT + self-administered treatment Holmberg et al. (2007) Phobic postural vertigo 20-one-year follow-up of the study above (Holmberg et al., 2006) Physical exercises/Vestibular rehabilitation therapy

Control Therapy Assessments Results
None Our data demonstrate that the majority of patients show beneficial effects in all VSS scores and in HADS anxiety scores at the follow-up 6 months after therapy. Figure 2 shows the change in (paired) scores after therapy. For the patients who fulfilled the criteria of PPPD, the change in the autonomic-anxiety subscore of the VSS (VSS-A) was larger than in the patients with other somatic diagnoses (p = .002).
It has to be kept in mind that-although patient numbers are high-the analysis is a simple follow-up observation and not a randomized, controlled trial. In addition, this study encompasses a follow-up time of 6 months. It would also be very interesting to analyze outcomes after a longer time interval, especially as some of other therapy studies have not been able to show a relevant long time effect (Holmberg et al., 2007). Therefore, we plan to perform a second survey after a longer time course of follow-up.
Both patient groups received the same therapy program. Thus, the therapy program was basically transdiagnostic and therefore may provide nonspecific benefits for patients with many vestibular disorders. The study protocol was not designed to detect diagnosis-specific effects. However, the readjustment of a dysfunctioning vestibular system can be of benefit in functional-, somatic-, and psychiatric-dominated conditions as well-in particular, a considerable overlap between these entities exists .
Moreover, the relatively high portion of PPPD patients (46.4%), who took part in the therapy program, is remarkable. That may be due to the fact that especially those patients with functional vestibular disturbances may be regarded as to profit from multimodal therapy. In addition, suited therapeutic offers are quite limited for patients with chronic dizziness in the outpatient setting.

| CON CLUS ION
Therapeutic principles to treat PPPD comprise cognitive-behavioral therapy, vestibular rehabilitation exercises, and medication (i.e., SSRI). Although therapy studies for PPPD and PPPD-like disturbances to date have been promising, large-scale, randomized, controlled trials are still missing. Follow-up observations of multimodal, interdisciplinary therapy programs that represent a concerted combination of different principles of therapy reveal an improvement in the symptoms of most patients with chronic dizziness. Thus, patients with PPPD and patients with other vestibular disorders benefit from these therapies. In our opinion, the concept of PPPD is most helpful for patients with chronic dizziness to provide a conceptual backbone for the planning and creation of multidisciplinary therapy programs.

ACK N OWLED G M ENTS
We thank Panagiota Karvouniari, German Center for Vertigo and Gait Disorders in Munich, for her thoughtful comments. Open access funding enabled and organized by ProjektDEAL.
F I G U R E 2 Change in scores before and 6 months after therapy week. (a) VSS. (b) HADS, (c) visual analog scale of intensity of dizziness and distress due to dizziness. The change is shown as 95% confidence interval and mean of differences. Note that these differences are calculated from pretreatment scores minus post-treatment scores. A clinical improvement is represented by a positive value of the difference

CO N FLI C T O F I NTE R E S T
The authors declare no financial or other conflicts of interest.

AUTH O R CO NTR I B UTI O N S
HA, OWW, and AGL conceptualized and designed the study. SF, AW, and HA collected the data. SF, HA, and CMK analyzed the data. HA and CMK drafted the manuscript. All authors critically reviewed and finally approved the manuscript.

PEER R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1002/brb3.1864.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.