Staab, Jeffrey P.

AbstractAutonomic, pain, limbic, and sensory processes are mainly governed by the central nervous system, with brainstem nuclei as relay centers for these crucial functions. Yet, the structural connectivity of brainstem nuclei in living humans remains understudied. These tiny structures are difficult to locate using conventional in vivo MRI, and ex vivo brainstem nuclei atlases lack precise and automatic transformability to in vivo images. To fill this gap, we mapped our recently developed probabilistic brainstem nuclei atlas developed in living humans to high‐spatial resolution (1.7 mm isotropic) and diffusion weighted imaging (DWI) at 7 Tesla in 20 healthy participants. To demonstrate clinical translatability, we also acquired 3 Tesla DWI with conventional resolution (2.5 mm isotropic) in the same participants. Results showed the structural connectome of 15 autonomic, pain, limbic, and sensory (including vestibular) brainstem nuclei/nuclei complex (superior/inferior colliculi, ventral tegmental area‐parabrachial pigmented, microcellular tegmental–parabigeminal, lateral/medial parabrachial, vestibular, superior olivary, superior/inferior medullary reticular formation, viscerosensory motor, raphe magnus/pallidus/obscurus, parvicellular reticular nucleus‐alpha part), derived from probabilistic tractography computation. Through graph measure analysis, we identified network hubs and demonstrated high intercommunity communication in these nuclei. We found good (r = .5) translational capability of the 7 Tesla connectome to clinical (i.e., 3 Tesla) datasets. Furthermore, we validated the structural connectome by building diagrams of autonomic/pain/limbic connectivity, vestibular connectivity, and their interactions, and by inspecting the presence of specific links based on human and animal literature. These findings offer a baseline for studies of these brainstem nuclei and their functions in health and disease, including autonomic dysfunction, chronic pain, psychiatric, and vestibular disorders.

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation.

Abstract Objective The purpose of this study was to determine the association between fear-avoidance beliefs and disability in 3 months in people with vestibular disorders while accounting for demographic and clinical characteristics. Methods This prospective cohort study included people aged 18 to 100 years who reported dizziness. Participants were recruited from a balance disorders clinic and outpatient physical therapy clinics. All participants completed the Vestibular Activities Avoidance Instrument (VAAI) and the Hospital Anxiety and Depression Scale at baseline and the Vestibular Activities and Participation measure (VAP), dizziness Visual Analogue Scale (VAS), and 12-item Short Form Health Questionnaire at baseline and 3-month follow-up. A modified version of the VAAI included 9 items abstracted from the 81-item VAAI. The relationships between 9-item VAAI scores and follow-up measures of disability were assessed using Spearman correlation coefficients. Linear regression models were analyzed to determine the effect of fear-avoidance beliefs on follow-up VAP score while accounting for baseline outcome measures. Results All participants (n = 404) completed the baseline assessment (mean age = 54 years), and 286 (71%) completed the 3-month assessment. The mean 9-item VAAI score was 25 (SD = 14) at baseline and was significantly associated with VAP (ρ = 0.54), 12-item Short Form Health Questionnaire component scores (ρ = −0.53; −0.44), and dizziness VAS at follow-up (ρ = 0.37). Approximately 38% of the variation in VAP score at follow-up was predicted by age, number of medications, 9-item VAAI score, dizziness VAS, and Hospital Anxiety and Depression Scale-depression score when considered together (R2 = 0.38). Conclusion Fear-avoidance beliefs are associated with measures of disability at 3 months and are predictive of activity limitations and participation restrictions at 3 months when controlling for age, medications, baseline dizziness, and depression symptom severity in people with vestibular disorders. Impact Measurement of fear-avoidance beliefs may provide important prognostic information, suggesting that an assessment of fear-avoidance beliefs could be used by clinicians to identify individuals at greater risk of disability after a vestibular disorder. Lay Summary Fear-avoidance beliefs in people who have vestibular disorders are associated with disability at 3 months and predict limitations in daily activities at 3 months.

Objective: The Dizziness Handicap Inventory (DHI) is a 25-item self-report quantifying dizziness-related physical and emotional symptoms and restrictions in daily activities. DHI scores do not correlate with severity of structural vestibular deficits; thus, high DHI scores may reflect other causes of morbidity. This study investigated the relationship between total DHI scores and the presence of structural, functional, and psychiatric disorders in tertiary neurotology patients. Study Design: Retrospective. Setting: Tertiary center. Patients: Eighty-five patients who underwent multidisciplinary neurotologic evaluations. Intervention: Diagnostic. Main Outcome Measure(s): Active illnesses identified by a multidisciplinary neurotology team were abstracted from medical records, cataloged as structural, functional, or psychiatric disorders, and used to group patients into diagnostic categories: structural (structural disorders only), functional (functional disorders with/without structural disorders), and psychiatric (psychiatric disorders with/without other conditions). DHI scores were compared across diagnostic categories. Sensitivities and specificities of DHI scores for identifying structural versus functional or psychiatric disorders were calculated. Results: Mean DHI scores differed significantly by diagnostic category (structural 35 ± 18, functional 64 ± 15, and psychiatric 65 ± 19), before and after adjusting for age and sex ( p < 0.001, Hedges’ g>1.62 for structural versus functional and psychiatric categories). DHI≤30 (mild handicap) had specificity = 0.98 for structural disorders alone, whereas DHI>60 (severe handicap) had specificity = 0.88 for functional or psychiatric disorders. Conclusions: In this tertiary cohort, categories of illnesses had large effects on total DHI scores. Patients with scores ≤30 were likely to have structural disorders alone, whereas those with scores >60 were likely to have functional or psychiatric disorders, with or without coexisting structural conditions.

We present diagnostic criteria for mal de débarquement syndrome (MdDS) for inclusion into the International Classification of Vestibular Disorders. The criteria include the following: 1] Non-spinning vertigo characterized by an oscillatory perception (‘rocking,’ ‘bobbing,’ or ‘swaying’) present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours. MdDS may be designated as “in evolution,” if symptoms are ongoing but the observation period has been less than 1 month; “transient,” if symptoms resolve at or before 1 month and the observation period extends at least to the resolution point; or “persistent” if symptoms last for more than 1 month. Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety. Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed. Motion-moderated oscillatory vertigo can also occur without a motion trigger, typically following another vestibular disorder, a medical illness, heightened psychological stress, or metabolic disturbance. Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD. Further research is needed into its phenomenological and biological relationship to MdDS, PPPD, and other vestibular disorders.

A growing body of clinical and epidemiological evidence supports a specific relationship between vestibular symptoms and migraine. Without a biomarker or complete understanding of pathophysiology, diagnosis of vestibular migraine (VM) currently depends upon symptoms in two dimensions: episodic vestibular symptoms temporally related to migraine symptoms. The Bárány Society and the International Headache Society have recently developed consensus diagnostic criteria. However, many issues remain unsettled, including the type, duration, and timing of vestibular symptoms related to headache that should be required for diagnosing VM. This paper focuses on the challenging third dimension of comorbidity, a frequent cause of diagnostic uncertainty that may confound clinical application and research validation of VM criteria. Several other neurotologic conditions occur more frequently in migraineurs than controls, including benign paroxysmal positional vertigo, Ménière's disease, and motion sickness. Patients with VM also have high rates of chronic subjective dizziness, which may be associated with anxious, introverted temperaments that can affect clinical presentation and treatment response. Broadly inclusive studies of well-characterized patients with other neurotologic and psychiatric comorbidities are needed to fully understand how vestibular symptoms and migraine interact in order to truly validate vestibular migraine, distill its essential features, define its boundaries, and characterize overlapping comorbidities.

Recent years have witnessed an upsurge of interest in migraine as a cause of vestibular symptoms. Starting with 1970s case reports linking migraine to childhood vertigo, neurotologists worldwide have increasingly diagnosed migraine. Various syndromes of vestibular migraine (VM) have been described, diagnostic criteria proposed, epidemiologic data collected, and neurophysiologic models developed. Yet, the concept that migraine causes vestibular symptoms rests on a surprisingly thin research database. Current concepts of VM are based on expert opinion, not empirical data. No general consensus exists about the definition of VM. No studies have analyzed its essential features. Just one well-controlled medication trial has been published. No biomarkers are known. To stimulate more rigorous research, this paper poses three questions about clinical investigations into migraine and vestibular symptoms: What variables should be measured? What patients should be studied? How might clinical trials yield both clinically useful results and greater insights into pathophysiologic processes? Using these questions, the limits of current knowledge are explored. Applicable research methods from epidemiology to genetics are examined. Pilot data demonstrating pharmacologic and genetic dissection techniques are presented. Ambitious, but practical, near-term clinical research goals are enumerated, including rigorous validation of diagnostic criteria and development of empirically derived management guidelines.