Validation of a comprehensive diagnostic algorithm for patients with acute vertigo and dizziness.

BACKGROUND AND PURPOSE: Vertigo and dizziness are common complaints in emergency departments and primary care, and pose major diagnostic challenges due to their various underlying etiologies. Most supportive diagnostic algorithms concentrate on either identifying cerebrovascular events (CVEs) or diagnosing specific vestibular disorders or are restricted to specific patient subgroups. The aim of the present study was to develop and validate a comprehenisve algorithm for identifying patients with CVE and classifying the most common vestibular disorders. METHODS: The study was conducted within the scope of the "PoiSe" project (Prevention, Online feedback, and Interdisciplinary Therapy of Acute Vestibular Syndromes by e-health). A three-level algorithm was developed according to international guidelines and scientific evidence, addressing both the detection of CVEs and the classification of non-vascular vestibular disorders (unilateral vestibulopathy, benign paroxysmal positional vertigo, vestibular paroxysmia, Menière's disease, vestibular migraine, functional dizziness). The algorithm was validated in a prospectively collected dataset of 407 patients with acute vertigo and dizziness presenting to the Emergency Department at the Ludwig-Maximilian University of Munich. RESULTS: The algorithm assigned 287 of 407 patients to the correct diagnosis, corresponding to an overall accuracy of 71%. CVEs were identified with high sensitivity of 94%. The six most common vestibular disorders were classified with high specificity, above 95%. Random forest identified presence of a paresis, sensory loss, central ocular motor and vestibular signs (HINTS [head impulse test, nystagmus assessment, and test of skew deviation]), and older age as the most important variables indicating a cerebrovascular event. CONCLUSIONS: The proposed diagnostic algorithm can correctly classify the most common vestibular disorders based on a comprehensive set of key questions and clinical examinations. It is easily applied, not limited to subgroups, and might therefore be transferred to broad clinical settings such as primary healthcare.

Recurrent Vertigo of Childhood: Clinical features and prognosis.

Introduction: "Recurrent Vertigo of Childhood" (RVC) has recently replaced the term "Benign Paroxysmal Vertigo of Childhood" and was defined as recurrent spells of vertigo without evidence of a vestibular migraine of childhood (VMC). RVC and VMC are considered the most frequent causes of vertigo and dizziness in children below 18 years of age. Diagnosis might be challenging since clinical features of RVC and VMC may overlap. Objective: This study aims to characterize clinical and instrument-based findings in patients with RVC and to evaluate the course of the disorder. Methods: We prospectively collected clinical and instrument-based data of children/adolescents younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich. All patients underwent a comprehensive neurological, ocular motor, vestibular and cochlear examination. Furthermore, findings from follow-up examinations were analyzed. Results: Overall 42 children (24 male and 18 female) with RVC were included in the study. The mean age at diagnosis was 7 ± 3.6 years with a mean onset of symptoms at the age of 5.6 ± 3.4 years. Attack duration ranged between 1 min and 4 h. The most common accompanying symptoms included nausea, vomiting, expression of fear, and falls. Non-migrainous headaches were reported by 11 patients during initial presentation, 7 of whom were later diagnosed with migraine. Female patients showed a higher age at symptom onset, a higher attack frequency, and attack duration. Eleven of the 24 patients seen at a 3.5 year follow-up reported a complete cessation of attacks. Patients still experiencing vertigo attacks had a significantly reduced attack frequency, especially those who implemented at least one prophylactic measure. Conclusion: A precise characterization of symptoms is essential for diagnosing children with RVC. Age at symptom onset does not exceed the age of 12. Gender-specific differences should be considered and may further support the evidence of an association with migraine. The disease course of RVC is benign, nevertheless implementing prophylactic measures such as regular exercise, increased fluid intake, sleep hygiene, and relaxation exercises, can improve attack frequency.

Episodic ataxias in children and adolescents: Clinical findings and suggested diagnostic criteria.

Background: The main clinical presentation of episodic ataxias (EAs) consists of vertigo and dizziness attacks lasting for minutes to hours with widely varying accompanying symptoms. The differentiation of EA and episodic vertigo/dizziness syndromes in childhood and adolescence such as vestibular migraine (VM) and recurrent vertigo of childhood (RVC) can be challenging. Furthermore, only few prospective studies of children/adolescents with EA are available. Objective: This study aims to characterize clinical and instrument-based findings in EA patients under 18 years of age, to delineate the clinical and therapeutic course in EA, and to present potentially new genetic mutations. Furthermore, the study aims to differentiate distinct characteristics between EA, VM, and RVC patients. Methods: We prospectively collected clinical and instrument-based data of patients younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich with EA, VM, or RVC between January 2016 and December 2021. All patients underwent a comprehensive evaluation of neurological, ocular-motor, vestibular and cochlear function, including video-oculography with caloric testing, video head impulse test, vestibular evoked myogenic potentials, posturography, and gait analysis. Results: Ten patients with EA, 15 with VM, and 15 with RVC were included. In EA the main symptoms were vertigo/dizziness attacks lasting between 5 min and 12 h. Common accompanying symptoms included walking difficulties, paleness, and speech difficulties. Six EA patients had a previously unknown gene mutation. In the interictal interval all EA patients showed distinct ocular-motor deficits. Significant differences between EA, VM, and RVC were found for accompanying symptoms such as speech disturbances and paleness, and for the trigger factor "physical activity". Furthermore, in the interictal interval significant group differences were observed for different pathological nystagmus types, a saccadic smooth pursuit, and disturbed fixation suppression. Conclusion: By combining clinical and ocular-motor characteristics we propose diagnostic criteria that can help to diagnose EA among children/adolescents and identify patients with EA even without distinct genetic findings. Nevertheless, broad genetic testing (e.g., next generation sequencing) in patients fulfilling the diagnostic criteria should be conducted to identify even rare or unknown genetic mutations for EA.

Semiquantitative 3T Brain Magnetic Resonance Imaging for Dynamic Visualization of the Glymphatic-Lymphatic Fluid Transport System in Humans: A Pilot Study.

OBJECTIVES: Recently, a novel clearing system for interstitial solutes of the brain was described as a perivascular pathway named the glymphatic system. Furthermore, lymphatic vessels were found in the meninges to drain interstitial fluids. It is hypothesized that interstitial solutes, such as amyloid ß, are firstly processed through the brain by the glymphatic system and secondly drained out of the brain by lymphatic vessels (glymphatic-lymphatic fluid transport system [GLS]). Since then, various neurological disorders, such as Alzheimer disease, have been associated with a dysfunction of the GLS. In the current study, we aimed to establish a clinical magnetic resonance imaging (MRI) study protocol for visualizing lymphatic vessels as part of the GLS in humans. More importantly, we aimed to describe the dynamic changes of a contrast agent in these lymphatic vessels over time. MATERIALS AND METHODS: Twenty volunteers with an unremarkable neurological/psychiatric history were included in this 3T MRI study. Serial MRI sequence blocks were performed at 3 predefined time points (TPs): TP 1, precontrast MRI before administration of a gadolinium-based contrast agent (GBCA); TP 2, immediately post-GBCA (early ce-MRI); and TP 3, 60 minutes post-GBCA (late ce-MRI). Each MRI block contained the following sequences obtained in the same order: whole-brain 3D T1-MPRAGE, whole-brain 3D T2-FLAIR, focused 2D T2-FLAIR, and whole-brain 3D T1-SPACE. Signal intensity (SI) in compartments of the GLS adjacent to the superior sagittal sinus, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was calculated by manually placed regions of interest. The time course of the signal intensities was examined by generalized linear mixed models. The data were adjusted for age, cognitive function (Montreal-Cognitive-Assessment test), and sleep quality (Pittsburgh Sleep Quality Index questionnaire). RESULTS: The GLS was best visualized in the 2D T2-FLAIR and 3D T1-SPACE sequences, enabling further SI measurement. In precontrast (TP 1), the SI within the GLS was significantly higher than in CSF and significantly lower than in GM and WM. In post-GBCA, a significant increase (TP 2) and decrease (TP 3), respectively, of the GLS SI values were noted (86.3 ± 25.2% increase and subsequent decrease by 25.4 ± 9% in the 3D T1-SPACE sequence). The SI values of CSF, GM, and WM did not change significantly between the 3 TPs. CONCLUSIONS: A clinical MRI study protocol was established for the visualization of lymphatic vessels as an important part of the GLS and therefore the brain's clearing mechanism of interstitial solutes. Furthermore, dynamic changes in the GLS were described over time, possibly reflecting the clearing function of the GLS. This might constitute the basis for evaluating the GLS function in manifold neurological pathologies in the future.