Effect of Self-treatment of Recurrent Benign Paroxysmal Positional Vertigo: A Randomized Clinical Trial.

Importance: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo with frequent recurrences. Objective: To determine the efficacy of a web-based diagnosis and treatment of BPPV when it recurs in patients with confirmed and treated BPPV. Design, Setting, and Participants: This randomized, controlled, parallel-group, double-blind trial took place in multiple referral-based university hospitals in South Korea between July 2017 and February 2020. Of 728 patients (age ≥20 years) with diagnosed and treated BPPV, 585 were enrolled after excluding 143 who declined participation, could not use the internet, or had spinal problems, multicanal BPPV, or cognitive dysfunction. Patients were followed up for recurrence at least for 2 years until February 2022. Interventions: Patients were randomly assigned (1:1) to the treatment or control group. The patients in the treatment group completed a questionnaire for diagnosis and received a video clip for self-administration of canalith repositioning maneuver (CRM) according to the type of BPPV diagnosed when they experienced positional vertigo again. Patients in the control group received a video clip for self-administration of CRM according to the type of BPPV that had been diagnosed on enrollment. Main Outcomes and Measures: The primary outcome was self-reported resolution of positional vertigo post-CRM. Secondary outcomes included difficulties and requirement for assistance when using the program and any falls or other adverse events related to CRM. The primary outcome was analyzed using both intention-to-treat and per-protocol methods. Results: Of 585 patients enrolled, 292 were randomized to the treatment group (mean [SD] age, 60.3 [12.8] years, 37 [64%] women) and 293 were randomized to the control group (mean [SD] age, 61.1 [13.2] years; 50 [71%] women). Overall, 128 (21.9%) had recurrence (58 in the treatment group and 70 in the control group), and 109 (85.2%) successfully used the web-based system. In the intention-to-treat analysis, 42 of 58 individuals (72.4%) in the treatment group and 30 of 70 individuals (42.9%) in the control group reported vertigo resolution (χ2 test: 95% CI, 0.13-0.46; P < .001). Conclusions and Relevance: This trial proved the efficacy of a web-based system for the diagnosis and treatment of recurrent BPPV. Use of this system may play an important role in telemedicine for vestibular disorders. Trial Registration: Clinical Research Information Service Identifier: KCT0002364.

Predictive value of free fatty acid levels in embolic stroke of undetermined source: A retrospective observational study.

The present study aimed to investigate the predictive value of free fatty acid (FFA) in embolic stroke of undetermined source (ESUS) according to the presence of potential embolic sources (PES) after extensive etiologic evaluation.This was a retrospective observational study based on a single-center registry from January 2011 to July 2017. Stroke subtypes were determined through laboratory findings, brain, and angiographic imaging, carotid ultrasonography, transthoracic echocardiography, and 24-hour Holter monitoring. If ESUS was suspected, transesophageal echocardiography was additionally performed. Patients were classified into ESUS with PES and ESUS without PES. PES included mitral annular calcification, mitral valve prolapse, patent foramen ovale, atrial septal aneurysm, spontaneous echo contrast, ventricular aneurysm, and high-risk plaques of aortic arch, or carotid bulb. We compared clinical and laboratory findings between the two groups.Of a total of 110 ESUS patients, 61 patients (55.5%) had no PES. Patients with ESUS without PES had higher levels of serum FFA, systolic blood pressure, diastolic blood pressure (DBP), and left atrial (LA) enlargement compared with those of ESUS with PES. Multivariable analysis demonstrated that the FFA level, DBP, and LA volume index were associated with ESUS without PES [odds ratio (OR) 1.038, 95% confidence interval (CI) 1.019-1.058 for FFA/10 µEq/L, OR 1.414, 95% CI 1.037-1.928 for DBP/10 mm Hg, and OR 1.073, 95% CI 1.009-1.141 for LA volume index].Higher levels of FFA, DBP, and LA volume index are associated with ESUS without PES, highlighting the need to identify the role of these markers in ESUS through further large-scale, multi-center and prospective studies.

Prevention of benign paroxysmal positional vertigo with vitamin D supplementation: A randomized trial.

OBJECTIVE: To assess the effect of vitamin D and calcium supplementation in preventing recurrences of benign paroxysmal positional vertigo (BPPV). METHODS: We performed an investigator-initiated, blinded-outcome assessor, parallel, multicenter, randomized controlled trial in 8 hospitals between December 2013 and May 2017. Patients with confirmed BPPV were randomly assigned to the intervention (n = 518) or the observation (n = 532) group after successful treatment with canalith repositioning maneuvers. The primary outcome was the annual recurrence rate (ARR). Patients in the intervention group had taken vitamin D 400 IU and 500 mg of calcium carbonate twice a day for 1 year when serum vitamin D level was lower than 20 ng/mL. Patients in the observation group were assigned to follow-ups without further vitamin D evaluation or supplementation. RESULTS: The intervention group showed a reduction in the ARR (0.83 [95% confidence interval (CI), 0.74-0.92] vs 1.10 [95% CI, 1.00-1.19] recurrences per 1 person-year) with an incidence rate ratio of 0.76 (95% CI, 0.66-0.87, p < 0.001) and an absolute rate ratio of -0.27 (-0.40 to -0.14) from intention-to-treat analysis. The number needed to treat was 3.70 (95% CI, 2.50-7.14). The proportion of patients with recurrence was also lower in the intervention than in the observation group (37.8 vs 46.7%, p = 0.005). CONCLUSIONS: Supplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV.

Ophthalmoplegia with skin necrosis after a hyaluronic acid filler injection.

Hyaluronic acid filler injection is commonly used for aesthetic purposes. However, many clinicians neglect the possibility of developing vascular occlusion and its devastating sequelae. Besides visual loss after iatrogenic ophthalmic artery occlusion, ophthalmoplegia without blindness is rare but may occur. Here, we report a 23-year-old woman with ptosis, lateral deviation of the right eye, and skin necrosis after hyaluronic acid filler injection. After hyaluronidase injection and steroid pulse therapy, ptosis and eye movement were completely restored. Skin necrosis was treated with a human epithelial growth factor ointment, followed by Nd:YAG laser. Complete healing with minimal scar was achieved.

Do thrombolysis outcomes differ between anterior circulation stroke and posterior circulation stroke? A systematic review and meta-analysis.

BACKGROUND: It remains unclear whether thrombolysis outcomes can be influenced by the affected vascular territory (i.e. anterior circulation stroke vs. posterior circulation stroke) in stroke patients owing to the lack of randomized controlled trials. AIMS: Using multiple comprehensive databases, we searched for observational studies of the safety and efficacy of intravenous thrombolytics and intra-arterial treatment with or without intravenous thrombolytics in accordance with the affected vascular territory. We performed a systematic review and meta-analysis. We evaluated symptomatic intracerebral hemorrhage, all-type intracerebral hemorrhage, mortality, and functional outcomes at three months. The recanalization rate was assessed in the intra-arterial treatment group. SUMMARY OF REVIEW: Twenty-one studies including a report from our own stroke registry were included through quantitative synthesis. Compared with the anterior circulation stroke group, the posterior circulation stroke group had a lower risk of ICH, including symptomatic intracerebral hemorrhage and all-type intracerebral hemorrhage, after intravenous thrombolytics and tended to have favorable functional outcomes at three months. Mortality was similar between the two groups. Regarding intra-arterial treatment, the symptomatic intracerebral hemorrhage and post-procedural recanalization rates were comparable between the two groups, although the posterior circulation stroke group had a higher mortality risk and lower tendency for a favorable functional outcome. CONCLUSIONS: Safety and efficacy of thrombolysis in posterior circulation stroke depends on involvement of large vessel occlusion and reperfusion modality such that intravenous thrombolytics is more effective and safer than in anterior circulation stroke; the safety and efficacy of intra-arterial treatment is comparable or lower than anterior circulation stroke. Considering the limitations of our meta-analysis, further studies are needed to provide high level evidence of a beneficial effect of intra-arterial treatment, and to identify patients' profiles associated with benefit of treatment.

Modulation of acquired monocular pendular nystagmus in multiple sclerosis: A modeling approach.

Acquired pendular nystagmus (APN) often occurs in association with the disorders affecting the visual system, such as multiple sclerosis (MS). The proposed mechanisms of APN in MS have been a delayed conduction of the visual information for ocular stabilization and unstable neural integrator for feedback controls. We determined the effects of visual inputs on the nystagmus intensity and the effects of saccades on phase shift of the nystagmus in a patient with monocular pendular nystagmus from MS. In this patient, (1) during binocular viewing in the light, the nystagmus was observed only in the eye with more severe visual loss, (2) the nystagmus disappeared in darkness, (3) monocular viewing with either eye markedly suppressed the nystagmus, (4) the nystagmus decreased when the visual inputs became less asymmetric between the eyes, and (5) saccades resulted in a phase shift of the nystagmus. From these results, we propose that the difference in the visual inputs between the eyes is responsible for monocular APN by disturbing visual integration and increasing instability of the feedback.

Abnormal Eye Movements in Parkinsonism and Movement Disorders.

Abnormal eye movements are commonly observed in movement disorders. Ocular motility examination should include bedside evaluation and laboratory recording of ocular misalignment, involuntary eye movements, including nystagmus and saccadic intrusions/oscillations, triggered nystagmus, saccades, smooth pursuit (SP), and the vestibulo-ocular reflex. Patients with Parkinson's disease (PD) mostly show hypometric saccades, especially for the selfpaced saccades, and impaired SP. Early vertical saccadic palsy is characteristic of progressive supranuclear palsy-Richardson's syndrome. Patients with cortico-basal syndrome typically show a delayed onset of saccades. Downbeat and gaze-evoked nystagmus and hypermetric saccades are characteristic ocular motor findings in ataxic disorders due to cerebellar dysfunction. In this review, we discuss various ocular motor findings in movement disorders, including PD and related disorders, ataxic syndromes, and hyperkinetic movement disorders. Systemic evaluation of the ocular motor functions may provide valuable information for early detection and monitoring of movement disorders, despite an overlap in the abnormal eye movements among different movement disorders.

Age-related deterioration of saccule-related neural function is associated with decreased estimated glomerular filtration rate and increased free thyroxine.

OBJECTIVE: This study attempted to identify systemic factors for age-related decline in neural function originating from the saccule using cervical vestibular-evoked myogenic potentials (cVEMP) parameters. METHODS: We recruited 129 symptomatic vertiginous patients who did not have known disorder affecting the cVEMP pathway (mean age = 52.4 ±â€¯13.9). The indicators of saccule-related neural function were the sum of normalized cVEMP amplitude (SNA) and the average of p13 latency on both sides (average latency, AL). Any associations between cVEMP and systemic factors were evaluated using a linear regression. RESULT: SNA decreased with ageing (p < 0.001) in univariable regression. The estimated glomerular filtration rate (eGFR) was positively associated with SNA (p = 0.002). Hematocrit, C-reactive protein, vitamin D, and free thyroxine (T4) showed a trend of association with SNA (p < 0.2). SNA was associated with ageing, increased free T4, and decreased eGFR in multivariable analysis. In the subgroup analysis, SNA was significantly associated with free T4 in younger patients (mean age = 41.5 ±â€¯9.91) but not in the older ones (mean age = 63.5 ±â€¯6.54). AL did not show any significant associations with systemic factors. CONCLUSION: Decreased eGFR and increased free T4 as well as aging may be risk factors for decline of saccule-related neural function. SIGNIFICANCE: Neural function originating from the saccule may be affected by systemic factors.

Genetic Variants Associated with Episodic Ataxia in Korea.

Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused by CACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.

Delayed vestibulopathy after heat exposure.

Even though dizziness is a common symptom of heat illness, comprehensive evaluation of the vestibular function has not been available in this potentially life-threatening disorder. Three patients developed vertigo about a week after heat exposure. Evaluation showed bilateral impairments of the vestibulo-ocular reflex during head impulses and the signs of vestibulocerebellar dysfunction that included spontaneous downbeat nystagmus, gaze-evoked nystagmus, and positional downbeat nystagmus. Exposure to excessive heat may give rise to delayed vestibulopathy by damaging the vestibulocerebellum.

Eye movement and vestibular dysfunction in mitochondrial A3243G mutation.

Studying eye movements and vestibular function would provide insights into brain networks that are vulnerable in mitochondrial disorders. We sought eye movement and vestibular abnormalities in three Korean patients with a mitochondrial A3243G point mutation. The patients suffered from vertigo and imbalance during the stroke-like and seizure episodes from lesions involving the posterior cerebral cortex, which were accompanied by bilateral saccadic hypermetria and horizontal gaze-evoked nystagmus. Furthermore, two patients showed bilateral impairments of the vestibulo-ocular reflex during head impulses for the horizontal and posterior canals on both sides in the absence of caloric paresis. Cerebellar atrophy was prominent on MRIs in two patients and was less marked in the other patient. These findings imply that the cerebellum is susceptible to neuronal energy deficiency due to mitochondrial A3243G point mutation.

Approach to dizziness in the emergency department.

Acute dizziness/vertigo is among the most common causes for visiting the emergency department. The traditional approach to dizziness starts with categorizing dizziness into four types: vertigo, presyncope, disequilibrium, and nonspecific dizziness. However, a recently proposed approach begins with classifying dizziness/vertigo as acute prolonged spontaneous dizziness/vertigo, recurrent spontaneous dizziness/vertigo, recurrent positional vertigo, or chronic persistent dizziness and imbalance. Vestibular neuritis and stroke are key disorders causing acute prolonged spontaneous dizziness/vertigo, but the diagnosis of isolated vascular vertigo has increased by virtue of developments in clinical neurotology and neuroimaging. However, a well-organized bedside examination appears more sensitive than brain imaging in diagnosing strokes presenting with acute dizziness/vertigo. A detailed history is vital to diagnose recurrent spontaneous dizziness/vertigo since confirmatory diagnostic tests are usually unavailable. Isolated positional vertigo is usually caused by benign paroxysmal positional vertigo, which can be treated at the bedside. In recent years, marked progress has occurred in the evaluation/management of acute dizziness/vertigo. However, even with developments in imaging technology, the diagnosis of acute dizziness/vertigo largely relies on bedside examination.

Recurrent posterior circulation infarction caused by anomalous occipital bony process in a young patient.

BACKGROUND: Structural anomaly of the cervical spine or craniocervical junction has been reported as one of the rare causes of ischemic stroke. We report a case of a young patient with recurrent posterior circulation infarction that may have been associated with an anomalous occipital bony process compressing the vertebral artery. CASE PRESENTATION: A 23-year-old man experienced recurrent posterior circulation infarction 5 times over a period of 5 years. He had no conventional vascular risk factors. Young age stroke work-up including thorough cardiac, intra- and extracranial vascular evaluation and laboratory tests for the hypercoagulable state or connective tissue disease yielded unremarkable results. An anomalous bony process from the occipital base compressing the left vertebral artery was observed on brain CT. All the recurrent strokes were explainable by the arterial thromboembolism originating from the compressed left vertebral artery. Therefore, the left vertebral artery compressed by the anomalous occipital bony process may have been the culprit behind the recurrent thromboembolic strokes in our patient. Intractable recurrent strokes even under optimal medical treatment led us to make a decision for the intervention. Instead of surgical removal of the anomalous occipital bony process, the left vertebral artery was occluded permanently by endovascular coiling after confirming that this would cause no neurological deficits or flow disturbance in the posterior circulation. There was no recurrence of stroke for 2 years after permanent occlusion of the left vertebral artery. CONCLUSION: Arterial thromboembolism originating from the left vertebral artery compressed by the anomalous occipital bony process is a rare but not to be overlooked cause of posterior circulation infarction. When intractable to medical treatment, endovascular occlusion of the vertebral artery without flow disturbance to the posterior circulation may be a useful treatment option when surgical removal is not feasible.