Focusing on patient related outcome measures (PROMs) in patients with vestibular and cerebellar disorders, this systematic review identified various scores available for the assessment of quality of life (QoL) related to vestibular and oculomotor complaints. Specifically, the DHI was found to be the most widely employed scale for evaluating vertigo or dizziness, surpassing the second-most used scale (PANQL) by a factor of 10, and exceeding the sum of the next five most commonly utilized scales by a factor of 3. Overall, there was significant heterogeneity in the patient populations studied and often poorly defined symptom-oriented diagnoses such as “unspecific dizziness or gait imbalance” (50.4% [53,769 of 106,723 patients]) or “vestibular disorders not further specified“ (7.9% [8’476 of 106’723 patients]) were used. Importantly, in the majority of studies the most commonly applied scales facilitated a statistically significant distinction between patient and control cohorts or different patient cohorts studied (77–100% depending on the scale used). However, the perceived value of self-reported metrics in monitoring disease progression or treatment response was more variable, considered helpful in 44 to 100% of studies (depending on the scale used, see Table 4 for details). In the following we will discuss the strengths and limitations of currently used QoL scores addressing oculomotor and/or vestibular complaints and put a special focus on their (future) use in patients with cerebellar ataxia (CA).

A Critical Review of the Most Commonly Used QoL Measures for Patients with Dizziness, Vertigo or Cerebellar Ataxia

The DHI aims to grade the subjective impact of dizziness on QoL [24]. It was developed to be employed in the context of vestibular disease and whilst it has good measurement properties and has been applied over a broad range of symptoms and diseases, a recent systematic review has highlighted some limitations. Specifically, in the studies identified in this systematic review evidence pertaining to the DHI’s content validity was either lacking or limited and of low quality and there was very limited evidence to support sufficient reliability of the DHI total score [46]. There is a single item in the DHI that may potentially relate to motion-induced oscillopsia, although it is rather non-specific (“Because of your problem, do you have difficulty reading?”). While the DHI is validated for symptoms of vestibular disease, it is not validated for patients with CA and in the research context has been rarely applied to CA patients [45].

This systematic review found that the VHQ and the UCLA-DQ were applied less frequently than the DHI for QoL assessment in dizzy patients. For the UCLA-DQ some studies reported good validity and reliability, while others did not [31, 47]. Other scales, such as the ABC, VAP, and VADL focus on activities of daily living that may be affected by dizziness such as mobility, fear of falling (ABC) and activities of daily living (VADL), but had limited (VADL) or absent (ABC) specificity to vertigo [24]. Several scales focused on visual symptoms, such as the NEI-VFQ (and its extensions), OFI, OS and OSQ. While vision is a crucial factor in evaluating the QoL of a patient experiencing dizziness and/or ataxia, it is not the sole determining factor. Thus, it is essential to consider the specialization of these scoring systems.

Discriminatory Value of QoL Scores Used in Dizzy and/or Ataxic Patients, and Their Role in Monitoring Disease Progression and Treatment Response

In a majority of studies included, the instruments applied demonstrated statistically significant differences between patients and controls, or between patient groups. This substantiates the role of the relevant tools in identifying the impact of vertigo, dizziness, or oculomotor symptoms on patient’s QoL. For the scales used in 10 or more studies (DHI, VADL, PANQL, ABC, VHQ and UCLA-DQ), a significant difference between patients and controls was reported in 77–100% of studies (depending on the tool used), with the highest values (> 95%) being for the UCLA-DQ and the ABC.

In this review, we gathered information on the authors’ perceived value of the scale(s) as applied in monitoring disease progression or treatment response. Focusing on longitudinal observational or interventional studies, the perceived value of the scores varied substantially. For the DHI, UCLA-DQ, VADL, VHQ and ABC 80% or greater of the studies reported that the scale(s) utilized were clinically valuable, however, the PANQL was only considered to be of benefit in a substantially lower fraction (44.4% of studies). Potential reasons for the lower rate of perceived utility of the PANQL by study authors include the design of the PANQL questionnaire, being less sensitive in detecting changes in QoL over time, and the natural course of disease in vestibular schwannoma (which is generally stable or slowly progressive such that no significant differences in response to various treatments (surgery vs. radiation therapy vs. expectant management) are seen).

The Value of Specific QoL Scores in Patients with Cerebellar Ataxia

With a special focus on developing a new QoL score focusing on the symptoms of oculomotor impairment in cerebellar and vestibular impairment in patients with CA (hereditary, sporadic, or acquired), we have compiled a subjective list of scores in order of perceived potential, which may serve as a basis for developing a new QoL score related to unsteadiness, oculomotor and vestibular involvement in CA patients.

NEI-VFQ-39 and NOS Extension of NEI-VFQ-25

The NEI-VFQ-39, a 39-item questionnaire, which is based on the VFQ-25 questionnaire [43], but includes an additional 14 items from the original 51-item version of the VFQ [48], is of particular interest given its application in three of the articles that we identified which reported on patients with cerebellar ataxias [35,36,37]. However, both the NEI-VFQ-39 and the NEI-VFQ-25 focus solely on the impact of vision-related symptoms on patients’ QoL and therefore neglect to consider other potential symptoms commonly experienced by those with CA. The NEI-VFQ-25 was designed to address QoL in patients with chronic ophthalmological diseases such as cataracts, glaucoma, age-related macular degeneration, diabetic retinopathy, or CMV retinitis. It is possible that a more comprehensive PRO for use in patients with CA could combine this with other scales such as the SODA [17]. It is also important to note that the NEI-VFQ-39 scoring system was not specifically designed for addressing visual or oculomotor symptoms typically seen in CA but rather for a wide range of neuro-ophthalmologic disorders. Nevertheless, it serves as a well-established questionnaire for assessing critical aspects of vision-related QoL [48].

A 10-item neuro-ophthalmologic extension (NOS) of the NEI-VFQ-25 questionnaire has been utilized in order to increase the questionnaire’s capacity to capture self-reported visual dysfunction in patients with neuro-ophthalmologic disorders [49]. This study included patients with optic neuritis, multiple sclerosis, idiopathic intracranial hypertension, ischemic optic neuropathy, stroke, ocular myasthenia gravis, ocular motor palsies, and thyroid eye disease. The NOS supplement demonstrated a capacity to capture self-reported visual dysfunction beyond that of the NEI-VFQ-25 alone [49]. Whilst appropriate degrees of internal consistency reliability were demonstrated, the patient cohort was of very varied pathology and it is likely, that few or no patients had certain oculomotor abnormalities commonly seen in CA such as spontaneous or gaze-evoked nystagmus. Additionally, these patients likely had intact vestibular function. While this scale includes relevant items such as blurred vision and double vision, there is an absence of items which could identify oscillopsia.

In patients with Friedreich Ataxia (FA), significant Pearson correlations (p≤0.01) between subitems of the NEI-VFQ-39 which relate to general vision and near activities, and the SLCLC (Sloan Low Contrast Letter Chart) were reported and correlated with decreased visual QoL. However, no such correlations were observed between the NEI-VFQ-39 and the Friedreich Ataxia Rating Scale (FARS) or commonly occurring oculomotor abnormalities in FA measures including angular Vestibulo-Ocular Reflex (aVOR) gain, the presence of saccadic eye pursuit or saccadic intrusions [35].

In a study reporting on visual system involvement in spinocerebellar ataxia (SCA) type 14, the patients rated their vision-related QoL in the NEI-VFQ (combining the original VFQ-25, the 14 questions from the appendix and the 10-item NOS proposed by Raphael and colleagues [49]) significantly worse than control subjects [37]. Importantly, only 3 out of 12 patients included in this study had oscillopsia.

In a study reporting on 19 SCA patients (11 SCA 3, 3 SCA 1 and 5 SCA 6), scores for the NEI-VFQ-25 and the NOS extension were significantly reduced in the patients compared to a reference population [36]. The authors concluded that the results of this study supported screening of SCA patients for visual disability. Impaired ocular stability on lateral gaze (“end-gaze nystagmus”) was reported in five out of 12 patients studied, however, none of these patients reported oscillopsia. Furthermore, no information was provided about vestibular properties, e.g., the integrity of the aVOR.

Oscillopsia Functional Impact Scale and Oscillopsia Severity Questionnaire

The Oscillopsia Functional Impact Scale (OFI) questionnaire exhibits similar limitations as the NEI-VFQ-39, given its exclusive focus on oscillopsia. While it is well-suited for evaluating the impact of oscillopsia on the patients’ QoL, other relevant balance-related symptoms of CA may be overlooked. Additionally, the authors of the questionnaire acknowledged the length of this instrument may pose a challenge and suggested the development of a more concise and practical version. Perhaps most importantly, the questionnaire’s test-retest reliability has yet to be evaluated [39].

The oscillopsia severity questionnaire (OSQ) was initially proposed for quantifying the oscillopsia severity in patients with bilateral vestibulopathy [4]. These authors found that the OSQ strongly correlated with the DHI and this may be viewed as support for its use in the assessment of oscillopsia severity in patients with bilateral vestibulopathy [4]. As the OSQ focuses on the severity of the symptom during ADLs, it does not specifically assess its impact on QoL. While the severity of oscillopsia may provide an indication of its impact on the patient’s QoL, this measure does not directly inquire about the patient’s ability to navigate in space independently and clearly perceive objects, especially during head movements.

Similarly, an oscillopsia questionnaire (OS) was developed as part of the BDC and was correlated to retinal slip in patients with bilateral vestibulopathy who presented with oscillopsia [40]. This oscillopsia questionnaire addresses both the severity of complaints (from “no difficulty” to “cannot do”) and their impact on QoL. It also specifically interrogates for oscillopsia triggered by head movements, and provides an oscillopsia score. The authors demonstrated that in these patients greater oscillopsia handicap scores were significantly correlated with a greater external locus of control, i.e., the perception of having little control over one’s health [40]. More recently, an Italian (unvalidated) version of this questionnaire was used in patients with either unilateral or bilateral vestibular hypofunction [41]. These authors demonstrated that functional vestibular testing (dynamic visual acuity, DVA) and the OS were highly correlated.

Visual Evaluation Protocol (VISATAX)

In a single study, patients with SCA 1, SCA 3, or FA were required to fill out a subjective Visual Evaluation Protocol (VISATAX) [38]. The authors demonstrated that the VISITAX score was increased in the majority of the patients studied (59%), being the highest in the SCA 3 group. Noteworthy, the VISATAX score was not correlated to any oculomotor parameter retrieved and no detailed information was provided on the prevalence of oscillopsia in this patient cohort.

Dizziness Handicap Inventory (DHI)

While the versatility of the DHI enables its use across various disorders [50], we hold the view that its scope is rather superficial and does not provide precise insight into the specific symptoms that significantly impact the CA patient. A single item (question F7 – “Because of your problem, do you have difficulty reading”?) addresses visual impairment, but not focusing on its occurrence while moving the head – i.e., not addressing typical situations that may trigger oscillopsia. As a matter of fact, in our review, it was only utilized in two studies involving a total of thirty patients who presented with CA and no validation of the DHI in CA was provided [45, 51].

Other Scores that have not Been Applied to CA Patients

The Glasgow Benefit Inventory (GBI) was designed to measure the improvement experienced by a patient following surgical or medical otolaryngology interventions for conditions including vestibular schwannoma. Therefore, it may be appropriate to use it if a CA patient undergoes an intervention that potentially improves (ataxic) gait, oscillopsia or deficits in the aVOR. However, outside of such circumstances, it does not appear to be a promising tool for the self-assessment of ataxia patients.

The Balance Disorder Checklist (BDC) presents an attempt to evaluate two crucial aspects of vestibular disease: balance impairment and specific visual symptoms, i.e., oscillopsia, while also considering the severity of the symptom and their impact on activities of daily living (ADLs). However, one potential limitation of the scale lies in its scoring method, which appears to vary between questions (requiring participants to indicate the dynamics of symptom onset for certain complaints (“spinning sensation” and “wobbling, jumping, or blurring of vision”) but not for others), possibly leading to increased complexity in its application and interpretation. Importantly, the reliability and internal consistency of this scale were assessed in a single study involving 12 patients with isolated peripheral bilateral vestibulopathy only, thereby necessitating further research to establish the scale’s robustness and validity in other diseases including CA [40]. Other scores identified in this systematic review such as the UCLA-DQ, the VHQ, the ABC scale, the Vestibular Activities and Participation Measure (VAP) and the VADL have not been used in patients with CA. Thus, their potential value for CA patients remains unclear and subject to further studies.

Overall, considering the available range of potential instruments for evaluating CA patients, it becomes evident that while several promising options exist, there is a notable absence of specific, validated instruments that comprehensively assesses the QoL of this particular patient group across various domains.

Key Items and Sub-Items in the Identified Scales Which Apply to Patients with Oscillopsia and/or CA

Scales with items of potential relevance in measuring PROs relating to QoL in individuals with CA scores include the oscillopsia score (OS) [40], the VISATAX score [38], the Oscillopsia Severity Questionnaire (OSQ) [4], the Oscillopsia Functional Impact Scale (OFI) [39], the Neuro-Ophthalmologic extension (NOS) of the NEI-VFQ-25 questionnaire [49] and the NEI-VFQ-39 questionnaire [48]. These scales have been hitherto applied to various patient populations including those with unilateral [41] or bilateral vestibular deficits [4, 40, 41], Friedreich Ataxia [35, 38], various SCAs (1, 3, 6, 14) [36,37,38], and neuroinflammatory diseases such as optic neuritis and multiple sclerosis [49]. While some scales such as the OS [40], OSQ [4] and the OFI [39] focus on oscillopsia, others address visual disturbances in a broader sense (including photophobia, difficulties focusing on objects, ptosis and diplopia) as e.g. the VISATAX [38], the NEI-VFQ-39 [43, 48] and the NOS of the NEI-VFQ-25 questionnaire [49]. Whereas all scores identified used Likert scales, they provided different types of questions, including agreement questions (NOS extension of the NEI-VFQ-25, NEI-VFQ-39), symptom intensity questions (VISATAX), questions focusing on difficulty handling certain situations (OS, NOS of the NEI-VFQ-25, NEI-VFQ-39) and frequency questions (OFI, OSQ, NOS of the NEI-VFQ-25, NEI-VFQ-39). Thus, these scales covered at least partially distinct aspects of PROMs related to oculomotor deficits and their impact of QoL. However, none of these scores had been specifically developed or validated in patients with CA (covering aspects such as internal consistency, content validity, test-retest reliability, discriminant ability, and responsiveness). Thus, these instruments are unable to capture the entire spectrum of oculomotor and balance symptoms typically observed in patients with CA, but rather, may identify a limited number of PROs. Therefore, developing a tool that specifically assesses the impact of oculomotor and balance deficits on QoL in patients with CA is strongly recommended. Traditionally employed scales in CA such as the SARA [14], ICARS [15] or the BARS [16] either do not address oculomotor symptoms (SARA), or do not address their impact on QoL (BARS, ICARS, SODA). However, the SODA [17] and the PROM ataxia [23] may serve as a starting point together with single items from scales designed to identify the impact of oscillopsia and gait imbalance on QoL in other diseases including bilateral vestibulopathy.

Limitations

While our systematic review has provided valuable insights into the utilization of QoL scores, there are several limitations that must be considered. Firstly, we encountered several studies that utilized ambiguous terminologies in their account of the primary symptoms and disease(s) studied. This required us to pool studies in more generic (and thus less specific) categories, potentially leading to a loss of granularity in our review. This limitation highlights the need for future research studies to adopt standardized terminologies and clear definitions (e.g. as proposed by the classification committee of the Bárány Society) [52]. Secondly, those scales which report on oscillopsia were implemented either in a limited number of studies or in some cases, only single studies. Thirdly, study sample sizes were not infrequently limited and often of mixed etiologies and the value of the PROM used – as indicated by the authors, reflects their judgement. Fourthly, while we assessed the impact of specific scores in distinguishing patients from controls, or between different patient groups (especially in CA patients), the important question of which instrument’s items contributed most to the ability to separate patients from controls was absent and so, the suitability of individual items to the construction of a future tool remains opaque.

Thus, while this systematic review has shed light on the utilization of PRO tools in dizzy and/or ataxic patients, the limitations of the study highlight the need for future research into the development of more suitable tools. This will enhance the validity and reliability of future clinical and research endeavors and addresses the unmet need for PROs.