Dizziness Handicap Inventory
The methods for the Dizziness Handicap Inventory (DHI) studies performed can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (32).
Headache Impact Test
The methods for the Headache Impact Test (HIT-6) studies performed can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (33,34).
Computerized Dynamic Posturography
The methods for the computerized dynamic posturography studies performed can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (35–37).
Neuropsychology Test Battery
Completion of a neuropsychology test battery preoperatively and at 3, 6, 9, and 12 months postoperatively that included: Beck Depression Inventory-II (BDI); Wide Range Intelligence Test (WRIT FSIQ) including average verbal (crystallized intelligence) and visual (fluid intelligence); Wide Range Assessment of Memory and Learning (WRAML-2), including the four domains of verbal memory, visual memory, attention/concentration, and working memory; and Delis–Kaplan Executive Function System. Detailed information regarding each of these neuropsychology tests can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351).
The scores from each test were analyzed by mixed design analysis of variance (ANOVA), with patient group (SCD, RWR, or both surgeries) as a between subjects factor and the test time (preoperative, early postoperative, and late postoperative times) as the repeated measures factor (SYSTAT 11 software). Least significant differences post-hoc tests were used for paired comparisons in cases where significant main or interaction effects were shown by ANOVA. A criterion of p < 0.05 was regarded as significant.
Although not the focus of the present study, once each patient completed their final surgical procedure and medical management resolved any of the factors complicating their postoperative recovery, their presenting symptoms and signs were returned near their baseline before developing SSCDS/OCDS. Additional information regarding the limitations of reporting the hearing and cVEMP outcomes can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (30). We completed quantitative comparisons of postural control using computerized dynamic posturography to better understand the changes in vestibular function as a consequence of surgical intervention using this more system-based approach.
The MRI with CISS sequences that demonstrated plugging of the superior semicircular canal in the 4 patients (patients 9–12) who subsequently developed no-iOCD and treated with RWR can be observed in Figure 1.
The neurobehavioral features of the patients attributed to neurological and psychiatric disorders (Tables 1 and 2) resolved over time (for example, see patients 1 and 2 (4,6)).
Dizziness Handicap Inventory
The DHI data revealed that there was a highly significant improvement pre- versus postoperatively (repeated measures ANOVA, F(1,11) = 254.6, p < 0.001) overall and for each group (Fig. 2), but no significant difference between patient groups (repeated measures ANOVA, F(2,11) = 1.8, p > 0.2). For the no-iOCD patients, the mean DHI score was 74 (range, 48–98, SD ± 17.48) preoperatively and 1.33 (range, 0–4, SD ± 1.63) postoperatively. This improvement was statistically significant (p < 0.001). For the both SCD and no-iOCD patients, the mean DHI score was 78.5 (range, 64–88, SD ± 11.0 preoperatively and 19.5 (range, 0–42, SD ± 19.1) postoperatively. This improvement was statistically significant (p < 0.001). For the SCD only patients, the mean DHI score was 72.5 (range, 68–76, SD ± 4.12 preoperatively and 8.5 (range, 4–18, SD ± 6.4) postoperatively. This improvement was statistically significant (p < 0.001).
The DHI physical subscores differed significantly across patient groups (repeated measures ANOVA, F(2,11) = 7.5, p < 0.01), despite the fact that all groups showed a significant reduction after surgery (repeated measures ANOVA, F(1,11) = 168.1, p < 0.001). This difference was because of a significantly higher postoperative subscore (least significant differences test) in the group given operations for both SCD plugging and subsequent no-iOCD RWR (7.00 ± 5.29 (SD)) than for either the SCD plugging alone (2.00 ± 1.63 (SD), p < 0.05) or no-iOCD with RWR alone (0.33 ± 0.82 (SD), p < 0.01) groups.
Headache Impact Test
Migraine headache was present in 88% (7/8) of subjects with no-iOCD only, 100% (4/4) of subjects with SCD and subsequent no-iOCD, and 80% (4/5) of subjects with SCD only. Interestingly for these patients the migraine headaches by clinical report resolved in all patients (4–6), including those with vestibular migraine, ocular migraine, and hemiplegic migraine (Table 2); however, the HIT-6 data revealed that there was a highly statistically significant improvement pre- versus postoperatively (p < 0.001) overall and between groups (Fig. 3), yet there are two patients who quantitatively became Class II and one patient remained a Class IV. The remaining 11 patients became Class I. For the no-iOCD patients, the mean HIT-6 score was 74 (range, 68–78 [all Class IV], SD ± 4 preoperatively and 45.7 (range, 42–49 [all Class I], SD ± 3.14) postoperatively. This improvement was statistically significant (p < 0.001). For the both SCD and subsequent no-iOCD patients, the mean HIT-6 score was 69.3 (range, 57–78 [one Class III, three Class IV], SD ± 9.7 preoperatively and 46.8 (range, 36–53 [two Class II and two Class I], SD ± 8.10) postoperatively. This improvement was statistically significant (p < 0.001). For the SCD only patients, the mean HIT-6 score was 69.8 (range, 61–76 [all Class IV], SD ± 6.34 preoperatively and 44.5 (range, 36–61 [one Class IV and three Class I], SD ± 11.27) postoperatively. This improvement was statistically significant (p < 0.001).
As shown in Table 1, 15 of 17 patients (88.2%) were diagnosed with migraine and/or migraine variants and managed medically using drugs to prevent migraine from occurring (e.g., topamax, zonegran, verapamil, or tricyclic antidepressants) before undertaking surgical intervention. For the no-iOCD patients (n = 7), the mean duration of treatment was 11.3 months preoperatively (range, 2–19 mo, SD ± 6.8 mo). For the both SCD and subsequent no-iOCD patients (n = 4), the mean duration of treatment was 19.8 months (range, 4–62 mo, SD ± 28.2 mo). For the SCD only patients (n = 4), the mean duration of treatment was 36.5 months (range, 14–60 mo, SD ± 21.2 mo).
Computerized Dynamic Posturography
Figure 4 shows the pre- versus postoperative posture performance for each group using the weighted composite score. Based on the independent samples Kruskal–Wallis test, there was no difference across groups for the preoperative or postoperative continuous EQ (CEQ) scores, either from the overall composite score or from the subscores for conditions 1 to 6. Although there were no significant differences in postoperative performance in each group analyzed separately, there was a significant improvement in postoperative composite score when combining all three groups (p = 0.044, Wilcoxon signed-rank test).
Beck Depression Inventory-II
The preoperative scores from the Beck Depression Index-II (BDI) indicated mild depression in all three groups. There was significant and parallel improvement to the minimal depression range after surgery in all three groups (F(1,18) = 9.8, p < 0.01), which appeared on the first postoperative test session (Fig. 5).
Wide Range Intelligence Test
No significant differences were found in Wide Range Intelligence Test (WRIT FSIQ) scores; including average verbal (crystallized intelligence) and visual (fluid intelligence) when comparing pre- and postoperative performance and also between the three groups.
Wide Range Assessment of Memory and Learning
The Wide Range Assessment of Memory and Learning-2 (WRAML), including the four subtests of verbal memory, visual memory, attention/concentration, and working memory, revealed differences in both the preoperative status and postoperative recovery among the patients with the no-iOCD only group treated with RWR, the SCD only group treated with plugging, and those with SCD treated with plugging who subsequently developed no-iOCD treated with RWR (Fig. 5).
For the verbal subtest, the SCD only group (plugging) showed a delayed improvement on the WRAML verbal subtest; it was significantly lower than the no-iOCD only group treated with RWR and the both SCD (plugging) and subsequently developed no-iOCD (RWR) group for the first postoperative test (ANOVA and then least significant differences tests). All three groups showed statistically significant improvement in the verbal subtest by the most recent neuropsychology test battery assessment (Fig. 5).
For the visual subtest, unlike patients with no-iOCD only (RWR) or both SCD (plugging) and subsequently developed no-iOCD (RWR) (Fig. 5), the SCD only (plugging) group did not show statistically significant improvement at either the initial or most recent postoperative testing session. They remained significantly lower than either of the other groups (analysis of variance with repeated measures on test times and a between groups factor of operative history, and then least significant difference tests). By contrast, there was a statistically significant improvement in the visual subtest scores for the no-iOCD only (RWR) group and the both SCD (plugging) and subsequently developed no-iOCD (RWR) group at both the initial postoperative assessment and the most recent assessment.
Preoperatively, the no-iOCD only (RWR) group showed abnormally low scores on the WRAML attention/concentration subtest (Fig. 5, 95% confidence interval of 55.271 to 91.229 re: normal of 100); however, the performance normalized after surgery. There were significant test time effects overall (improvement in all groups), initially (preoperative) worse in the SCD only (plugging) than the no-iOCD only (RWR) patients (p < 0.02, Fisher's Least Significant Difference [LSD] test), but the same afterward.
Analysis of WRAML of the Working Memory subtest revealed no significant differences preoperatively compared with the first and the most recent neuropsychology test battery assessments across all three groups.
Delis–Kaplan Executive Function System
Analysis of variance showed that there was significant postoperative improvement in both the Delis–Kaplan Executive Function System (D-KEFS) motor score (F(2,28) = 10.31, p < 0.01) and the number and letter score (F(2,28) = 6.04, p < 0.05). There were no significant differences between the treatment group responses (Fig. 6).
Discussion of the current limitations in reporting outcomes of surgical intervention in these patient cohorts can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (30,38,39).
Since the focus of this work was on understanding the degree of cognitive impairment and recovery after intervention, we elected to focus on two more global measures of vestibular function, the DHI and also the continuous equilibrium scores obtained via computerized dynamic posturography before and after intervention. As shown in Figure 2, the DHI data revealed that all patient groups reported a highly statistically significant perceived improvement for pre- versus postoperative status. On the other hand, dynamic posturography showed no significant differences in postoperative performance when each group was analyzed separately, despite a significant improvement in postoperative composite score when all three groups were combined. Hence, the groups did not differ clinically on these standard response metrics either pre- or postoperatively.
Most of the symptoms that disrupt the lives of patients with SCD, no-iOCD, and/or PLF are related to the severe, chronic, uncompensated asymmetric sensory deficits (3–7,9–12). The acute and chronic sequelae include direct and indirect sensorimotor processing, interoceptive, and cognitive neuronal networks that contribute to fear, anxiety, and altered cognitive performance. The relationship of these networks to vestibular information processing is described in detail in reviews (40,41).
These symptoms are, in part, a consequence of the fact that visual and vestibular sense-organs are anchored in the head. Sensations of visual motion and inertial motion are interpreted within the assumed context of stable head control. This assumption of head stability provides the basis for interpreting balance-related information from the head-fixed sensors in terms of the outside world. The perceptual assumption of stable motor control has two important implications. First, abnormal dynamic postural control can produce unexpected visual (e.g., optic flow or oscillopsia), head motion, or proprioceptive information. The autonomic and cognitive symptoms associated with these apparent sensory mismatches (including “visual-vestibular mismatch” all fall within the rubric described by the sensory conflict hypothesis for motion sickness, simulator sickness, and cybersickness (42–47)). Degradation of cognitive test performance would be expected.
Second, individuals with vestibular abnormalities may adapt functionally by relying on sensory signals that restore a relatively stable level of control. If balance control becomes more responsive to spatial information in the visual channel, a balance phenomenon referred to as visual balance dependence develops. This can be defined operationally as increased sway in response to full-field motion of the visual surround (“optic flow”), a phenomenon that has been observed in patients with primary vestibular disorders (48). If balance control becomes more responsive to somatosensory (tactile and proprioceptive) information, somatosensory dependence develops. These changes in relative central weighting of multisensory signals may have cognitive consequences. Treatment that resolves the sensorimotor control performance would be expected to normalize the cognitive consequences.
However, balance-related information also affects limbic and cortical networks related to anxiety and threat assessment (41,49). It is an open question whether resolution of the peripheral asymmetry alone is sufficient to reverse chronic, adaptive changes in cognition via these mechanisms.
Cognitive Functional Differences Between SCD and No-iOCD Patients
Further discussion of the cognitive differences between SCD and no-iOCD patients can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (50–59).
Clinically, cognitive alterations are nearly universal in patients with superior canal dehiscence syndrome, whether because of an actual SCD or a no-iOCD. In contrast to these disorders that result in gravitational receptor dysfunction type of vertigo, it is uncommon in patients with rotational receptor dysfunction type of vertigo such as with benign positional vertigo, vestibular neuronitis, or other disorders producing true rotational vertigo. Patients with a no-iOCD and/or SCD often use the following descriptors when describing their cognitive function: “fuzzy, foggy, spacey, out-of-it; memory and concentration are poor; difficulty reading – as if the words are floating on the page; trouble finding the right words; and forgetting what I wanted to say.”
Gurvich et al. (60) published an excellent review of the role of the vestibular system on cognition and psychiatry. The two key anatomical regions that provide links between the vestibular system and neural networks involved in cognitive and emotional processing are the parabrachial nucleus and the hippocampus (49,61–63); however, many of the neuroanatomical regions that are linked to the vestibular system are also implicated in several psychiatric illnesses. The past decade has observed an increased interest in the relationship between the vestibular system and mood, cognition and psychiatric symptoms with studies demonstrating vestibular stimulation can produce changes in mood, cognition, and psychiatric symptoms (64–66). It is also the case that many individuals with SCDS have been assigned a neurological or psychiatric diagnosis before their vestibular disorder was diagnosed and have experienced resolution of their “psychiatric disorder” after surgical intervention (4,5,9–11) (Table 1). This unfortunately is common with children (4,5). The hippocampus is consistently implicated in cognition and models of psychiatric disorders and there is a large body of evidence supporting vestibular–hippocampal interactions (67–71).
Smith et al. and Zheng et al. reported that modulation of memory, but not spatial memory, occurs with vestibular lesions and can be influenced by galvanic vestibular stimulation (72,73). These findings may lead to additional treatment strategies that may accelerate or maximize recovery after repairing a no-iOCD or SCD.
Further discussion of these issues from the historical perspective can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (74,75).
Altered Spatial Orientation
A discussion of the relationship between diseases producing otic capsule dehiscence syndrome and altered spatial orientation can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (76–79).
A discussion of the relationship between diseases producing otic capsule dehiscence syndrome and migraine headache can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (3–7,9–12,80–82) (also see Fig. 3 and Table 2).
Beck Depression Inventory-II
The preoperative scores from the BDI indicated mild depression in all three groups. There was significant and parallel improvement to the minimal depression range after surgery in all three groups (F(1,18) = 9.8, p < 0.01), which appeared on the first postoperative test session (Fig. 5). There were no significant differences between any of the three groups. These findings are not unexpected, as most of these patients have experienced a delay in diagnosis despite having observed several physicians and completed numerous diagnostic studies. Many have been told “it is all in your head” and their interpersonal relationships and work performance have also been threatened or adversely impacted. Many patients develop severe depression because of their inability to perform their normal tasks. As shown in Figure 5, this recovery is rapid and significantly better, even a few months after surgical intervention.
Wide Range Intelligence Test
The finding that the WRIT showed no change in IQ is not surprising and serves as an internal control for these subjects. It would not be expected that these chronic, uncompensated gravitational receptor asymmetries would alter inherent intelligence.
Wide Range Assessment of Memory and Learning
The WRAML, including the four subtests of verbal memory, visual memory, attention/concentration, and working memory, revealed differences in both the preoperative status and postoperative recovery among the patients with no-iOCD treated with RWR, SCD treated with SCD plugging only, and those with SCD and subsequent development of no-iOCD who required both SCD plugging and subsequent RWR (Fig. 5).
For the verbal and visual subtests, the SCD only (plugging) group recovered function differently than the no-iOCD only (RWR) group and the both the SCD (plugging) and subsequently developed no-iOCD (RWR) group (Fig. 5). This is likely multifactorial. It is not unexpected that the both SCD treated with SCD plugging and subsequent development of no-iOCD treated with RWR group recovered in a similar manner as each patient had time to undergo vestibular compensation after closing the superior semicircular canal dehiscence before determining that they also developed a new no-iOCD and treating that dehiscence with a RWR surgery. Table 1 shows that these SCD (plugging) patients who subsequently developed a no-iOCD and had RWR had a mean time from first SCD plugging surgery to most recent neuropsychology assessment of 18.75 months, whereas the SCD only group treated with SCD plugging was 9.6 months. It is possible that there is a finite amount of brain recovery or reorganization that occurs as a function of time and that the process of vestibular compensation delayed the recovery of memory and learning as reflected by WRAML visual and verbal subtests. It should be noted that the WRAML visual subtest scores worsened at the first postoperative assessment in the SCD only patients. It may be that improvement of vestibulomotor function was necessary via vestibular compensation to eliminate these “cognitive jamming” mechanisms before visual recovery could occur. There were also two children included in the SCD only cohort who had factors potentially impacting their test performance. There was a statistically significant improvement in the verbal and visual subtests for the no-iOCD only group treated with RWR and the both SCD and subsequent development of no-iOCD group treated with SCD plugging and RWR, respectively at both the initial postoperative assessment and the most recent assessment.
Although speculative, there are five additional mechanisms that could explain the differences in recovery that we observed in the SCD only group treated with plugging in both the visual and verbal domains: 1) direct vestibular processing effects; 2) erroneous or ambiguous motion information that creates an increased cognitive load for normal balance and navigation functions; 3) acute prodromal (e.g., Sopite syndrome [relates symptoms of fatigue, drowsiness, and mood changes to prolonged periods of motion]) and autonomic effects; 4) fear, anxiety, and phobic responses; and 5) parabrachial nucleus cells have both superior semicircular canal and linear acceleration sensitivity.
Preoperatively, the no-iOCD only (RWR) group showed abnormally low scores on the WRAML attention/concentration subtest (Fig. 5); however, the performance normalized after surgery. If a no-iOCD is at the modiolus, it would be expected that CSF pulsations would repeatedly stimulate the otolithic end-organs on the affected side whereas with a SCD there is no direct communication with the CSF, so perhaps it is the case that the no-iOCD patients have more ongoing impairment of attention/concentration. Ultimately, there were significant test time effects overall (improvement in all groups) by the most recent neuropsychology assessment.
Delis–Kaplan Executive Function System
Analysis of variance showed that there was significant postoperative improvement in both the D-KEFS motor score and the number and letter score. There were no significant differences between the treatment group responses (Fig. 6). This recovery of executive function was rapid and robust and not impacted by vestibular compensation as the no-iOCD patients experienced nearly immediate improvement anecdotally and our short-term follow-up intervals in the SCD only group treated with SCD plugging (4–7,9–11). These functions measured by the D-KEFS largely depend on prefrontal cortex.
A discussion of learning effects can be found in the Supplemental Digital Content (http://links.lww.com/MAO/A351) (83–85).
These data represent the first demonstration that cognitive dysfunction in patients with otic capsule defects resulting in OCDS, regardless of etiology, exist, can be measured and that improvements in depression and cognitive function can be accomplished with appropriate, targeted, vestibular surgery.
The authors thank Stuart Gardiner, Ph.D., for initial guidance with the statistical analysis strategy.
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Cognitive dysfunction; Depression; Memory; Migraine; Otic capsule dehiscence syndrome; Perilymph fistula; Superior canal dehiscence syndrome; Traumatic brain injury
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