Vestibulo-spatial navigation: pathways and sense of direction.

Aims of the present article are: 1) assessing vestibular contribution to spatial navigation, 2) exploring how age, global positioning systems (GPS) use, and vestibular navigation contribute to subjective sense of direction (SOD), 3) evaluating vestibular navigation in patients with lesions of the vestibular-cerebellum (patients with downbeat nystagmus, DBN) that could inform on the signals carried by vestibulo-cerebellar-cortical pathways. We applied two navigation tasks on a rotating chair in the dark: return-to-start (RTS), where subjects drive the chair back to the origin after discrete angular displacement stimuli (path reversal), and complete-the-circle (CTC) where subjects drive the chair on, all the way round to origin (path completion). We examined 24 normal controls (20-83 yr), five patients with DBN (62-77 yr) and, as proof of principle, two patients with early dementia (84 and 76 yr). We found a relationship between SOD, assessed by Santa Barbara Sense of Direction Scale, and subject's age (positive), GPS use (negative), and CTC-vestibular-navigation-task (positive). Age-related decline in vestibular navigation was observed with the RTS task but not with the complex CTC task. Vestibular navigation was normal in patients with vestibulo-cerebellar dysfunction but abnormal, particularly CTC, in the demented patients. We conclude that vestibular navigation skills contribute to the build-up of our SOD. Unexpectedly, perceived SOD in the elderly is not inferior, possibly explained by increased GPS use by the young. Preserved vestibular navigation in cerebellar patients suggests that ascending vestibular-cerebellar projections carry velocity (not position) signals. The abnormalities in the cognitively impaired patients suggest that their vestibulo-spatial navigation is disrupted.NEW & NOTEWORTHY Our subjective sense-of-direction is influenced by how good we are at spatial navigation using vestibular cues. Global positioning systems (GPS) may inhibit sense of direction. Increased use of GPS by the young may explain why the elderly's sense of direction is not worse than the young's. Patients with vestibulo-cerebellar dysfunction (downbeat nystagmus syndrome) display normal vestibular navigation, suggesting that ascending vestibulo-cerebellar-cortical pathways carry velocity rather than position signals. Pilot data indicate that dementia disrupts vestibular navigation.

Complex benign horizontal canal positional vertigo: new perceptual management.

OBJECTIVE: Horizontal semicircular canal site pathology of benign paroxysmal positional vertigo demonstrating three types of nystagmi on positional test were studied. We have attempted to design a protocol for its diagnosis and treatment. METHODS: 320 patients of HSC-BPPV were subjected to two types of positional tests. Of these, patients with bilateral steady apogeotropic nysatgmus were treated with VAV modification of Semont's maneuver. Patients with unsteady or changing apo/geotropic signs were converted into steady geotropic ones by repetitive positional tests; followed by barbecue maneuver with forced prolong positioning. RESULTS: Overall 88% of patients had a total recovery. 92% of patients with geotropic nystagmus showed no symptoms after second maneuveral sitting. 85% of patients with apogeotropic nystagmus recovered fully after third maneuveral sitting. CONCLUSIONS: Correct identification of subtypes of HSC-BPPV is based on provoked nystagmus by positional tests. After locating the site and side on the basis of nystagmic pattern, physician can apply the appropriate PRM. LEVEL OF EVIDENCE: II a.

Pendular Seesaw Nystagmus: Disappearance With Monocular Occlusion.

ABSTRACT: We report a case of pendular seesaw nystagmus caused by bitemporal hemianopia; the nystagmus disappeared while in darkness as previously described, but it also disappeared with monocular occlusion, which indicates the pivotal role of binocular vision in the pathogenesis.

Paraneoplastic cochleovestibulopathy: clinical presentations, oncological and serological associations.

OBJECTIVE: Cochleovestibulopathy is a distinguishable paraneoplastic phenotype. In this study, we evaluate clinical presentation, serological/cancer associations and outcomes of paraneoplastic cochleovestibulopathy. METHODS: Retrospective chart review of patients with hearing impairment and/or vestibulopathy who underwent serological evaluations for paraneoplastic antibodies between January 2007 and February 2021 was performed. RESULTS: Twenty-six patients were identified (men, n=23; median age, 45 years, range: 28-70). Biomarkers detected included: KLHL11-IgG| |(n=20,| |77% (coexisting LUZP4-IgG, n=8)),| ||ANNA1-IgG| | |(n=3,| |12%),| |amphiphysin-IgG|| |(n=2,| |8%)| |and| |LUZP4-IgG|| |(n=1,| |4%). Most common neoplastic association was |testicular|/|extra-testicular| |seminoma| | (n=13,| |50%).|| Hearing| impairment (bilateral, 62%) was |present| |in| |all| |patients.| |Fifteen patients (58%) had cochleovestibular dysfunction as their initial presentation before rhombencephalitis/encephalomyelitis manifestations (hearing loss, four; acute vertigo, eight; both, three). |Brain| |MRI| |demonstrated| |internal| |auditory| |canal| |enhancement| |in| |four |patients.| Audiometry commonly revealed severe-profound bilateral sensorineural hearing loss. Most patients |had| a refractory course |despite| |immunotherapy| |and/or| |cancer| |treatment|. CONCLUSION: Cochleovestibulopathy commonly presents with rapidly progressive bilateral hearing loss and/or acute vertigo. However, in some patients, these symptoms present along with or following brainstem/cerebellar manifestations. KLHL11-IgG and seminoma are the most common serological and cancer associations, respectively. Recognition of this phenotype may aid in earlier diagnosis of paraneoplastic autoimmunity and associated cancer.

Oncologic causes of oculopalatal tremors: neurophysiology and treatment.

Oculopalatal tremor (OPT) is an acquired pathology characterized by continuous and rhythmical soft palatal movements combined with pendular nystagmus. Aside from vascular lesions, oncological masses affecting the dentatorubro-olivary pathway can impair brainstem and/or cerebellar pathways, manifesting as dyssynchronous movement. In this review, we delve into the neurophysiology of OPT along with oncological causes and treatment options based on the most recent clinical trial data. This literature review includes medication treatment data from clinical trials enrolling individuals with features of OPT, including acquired pendular nystagmus (APN). Trials were deemed eligible for inclusion in this review if one or more participants had symptoms determined by the trial authors to be caused by OPT. Trials investigating the treatment of APN secondary to a separate cause, such as multiple sclerosis, were excluded from this review. Several early treatments failed to demonstrate a benefit for patients with APN due to OPT. Trials of anticholinergic agents were largely ineffective and poorly tolerated. Botulinum toxin A demonstrated improvement in APN symptoms. Most recently, trials including memantine and gabapentin have demonstrated success with attenuation of APN. Surgical modalities such as DBS have yet to show improvement, though with only a single case report as evidence. Oculopalatal tremor is a unique manifestation of posterior fossa tumors disrupting the Guillain-Mollaret triangle. Symptom control through medication management has had limited success attributed to poor response and medication intolerance. Surgical modalities like DBS may have an emerging role in OPT treatment by targeting dyssynchronous activity in the dentatorubro-olivary pathway.

Seesaw nystagmus with internuclear ophthalmoplegia from bilateral dorsomedial pons and left thalamus infarction: a case report.

BACKGROUND: We describe for the first time the clinical features and mechanisms of a bilateral dorsomedial pons and left thalamus infarction with seesaw nystagmus and internuclear ophthalmoplegia. CASE PRESENTATION: A 62-year-old Chinese man was hospitalized for sudden-onset dizziness, diplopia, and gait disturbance. A neurological examination revealed seesaw nystagmus and internuclear ophthalmoplegia. Magnetic resonance imaging disclosed an acute infarction confined to the bilateral dorsomedial pons and left thalamus. Subsequently, 2 weeks of antithrombotic therapy led to an improvement in his symptoms. CONCLUSIONS: This case illustrates that the acute onset of seesaw nystagmus and internuclear ophthalmoplegia accompanied by risk factors for cerebrovascular diseases are highly suggestive of brainstem infarction.

Central positional vertigo: A clinical-imaging study.

The diagnosis of central positional vertigo (CPV) is challenging, mainly because symptoms overlap with the common variants of benign paroxysmal positional vertigo (BPPV). Recent correlations of imaging with neurotologic exams have improved our understanding of CPV and ability differentiate it from BPPV. Yet, there is still a need to develop better diagnostic algorithms to improve timely diagnosis and early intervention. Here we present a retrospective review of the clinical characteristics, neurotologic evaluation and imaging of CPV in a cohort of 27 patients and propose a diagnostic algorithm to be tested in future prospective fashion. Most patients had positional nystagmus (downbeat and apogeotropic horizontal), cerebellar ocular motor abnormalities and truncal ataxia indicative of a central lesion. 61.5% of our cohort had paroxysmal CPV, 30.5% had a non-paroxysmal CPV and 8% paroxysmal-evolving-to-non-paroxysmal CPV. The most common pattern of positional nystagmus evoked with maneuvers was positional downbeat nystagmus (pDBN, 69.2%), apogeotropic horizontal nystagmus (42.3%), geotropic (7.69%) and multiplanar (23.0%). Notably, 13 (50%) of patients had cerebral imaging prior to CPV being on the differential diagnosis, whereas another 50% of patients had CPV diagnosis preceding their work-up. Unilateral lesions on imaging were 4× less likely to exhibit nausea and vomiting, nearly 2× less likely to exhibit paroxysmal nystagmus, and 2× less likely to exhibit nystagmus with habituality. Findings of pDBN or apogeotropic nystagmus alone were enough to diagnose CPV in 50% of our patient cohort, underscoring the importance of clinical evaluation in a time when an "imaging-first" philosophy is gaining popularity in Neurology.

Optokinetic Analysis in Patients With Spontaneous Horizontal Gaze-Evoked Nystagmus Without Radiological Neuropathology.

Gaze-evoked nystagmus is not rare among those who have acute balance problem and may indicate a cerebellar dysfunction that is associated with a broad spectrum of disorders. The aim of this study is to analyze optokinetic response in those patients. Eleven males and 7 females (age range: 25-60, 42.5 [9.75]) with gaze-evoked nystagmus were analyzed with optokinetic test (Micromed Inc). Nystagmus was elicited by a stimulator light spot moving across the patient's visual field at a target speed of 30 degree/second. Ten age-matched healthy participants served as controls. The gain and slow-phase velocity difference in oculomotor response from left and right stimulus was compared in patients and the control participants. One-way analysis of variance test was used for multiple variance analysis of the groups. Statistical significance was set at P < .05. Slow-phase velocity of gaze-evoked nystagmus was ranging between 6 and 19 degree/second. The mean slow-phase velocity of gaze-evoked nystagmus to the right and left was 8.1 (3.81) and 6.8 (4.67) degree/second, respectively. Optokinetic gain was out of normal limits in 10 (55.5%) patients. Comparison of mean gain difference between the patients and the normal participants was statistically significant (P = .025). No statistical difference was found in mean slow-phase velocity difference in optokinetic nystagmus between control participants and patients (P > .05 [.099]). An acute-onset balance problem may be associated with dysfunction of separate populations of neurons in the brainstem and cerebellum even if there is no radiological neuropathy since gaze-evoked nystagmus is a sign of neural integrator dysfunction. Patients with gaze-evoked nystagmus and optokinetic abnormalities may have disruption of cerebellar pathways and should be followed closely.

Seeing function in structure: "incidental" eye findings on OCT in a patient with multiple sclerosis.

A 17-year-old girl with relapsing-remitting multiple sclerosis (MS) was referred for a 2-year history of visual blurriness. Her bedside examination was remarkable for gait unsteadiness only. Optical coherence tomography was performed as part of her workup. Unexpectedly, Spectralis© video imaging revealed left torsional nystagmus that was not apparent on bedside examination. Review of previous brain magnetic resonance images (MRI) revealed left ocular deviation, as well as a left dorsolateral medullary MS plaque, which was the cause of her torsional nystagmus. We highlight how Spectralis© scanning confocal laser ophthalmoscopy allows video imaging that can capture torsional ocular movements.

Direction-Changing Positional Nystagmus in Acute Otitis Media Complicated by Serous Labyrinthitis: New Insights into Positional Nystagmus.

OBJECTIVE: To demonstrate characteristic nystagmus findings in acute otitis media (AOM) complicated by serous labyrinthitis and discuss the mechanism of direction-changing positional nystagmus (DCPN) in this condition. PATIENTS: A patient with AOM complicated by serous labyrinthitis on the left side. INTERVENTION: Video nystagmography and 3D fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: Characterize positional nystagmus in a head-roll test observing the change of nystagmus direction in process of time and compare findings of temporal bone 3D FLAIR MRI. RESULTS: A previously healthy 50-year-old man who complained of acute otalgia, hearing loss, and vertigo was diagnosed with AOM complicated by serous labyrinthitis on the left side. A head-roll test performed on the day when vertigo developed showed persistent geotropic DCPN. While pre- and postcontrast T1-weighted MRI showed no signal abnormality in both inner ears, 10-minute delay postcontrast 3D FLAIR image showed enhancement in the inner ear on the left side. Four-hour-delay postcontrast 3D FLAIR images showed more conspicuous enhancement of the whole cochlea, vestibule, and semicircular canals on the left side. CONCLUSIONS: In AOM complicated by serous labyrinthitis, density of perilymph may increase due to direct penetration of cytokines and other inflammatory mediators from the middle ear into perilymph and breakdown of blood-labyrinth barrier that causes vascular leakage of serum albumin into perilymph. The density difference between perilymph and endolymph makes the semicircular canal gravity sensitive. A buoyant force is also generated by gravity, causing indentation of endolymphatic membrane in the ampulla and cupula displacement. Thus, at the early stage of serous labyrinthitis, a head-roll test may elicit persistent geotropic DCPN, of which the direction can be changed over time.

The structure of mammalian ß-mannosidase provides insight into ß-mannosidosis and nystagmus.

ß-Mannosidase is a lysosomal enzyme from the glycosyl hydrolase family 2 that cleaves the single ß(1-4)-linked mannose at the nonreducing end of N-glycosylated proteins, and plays an important role in the polysaccharide degradation pathway. Mutations in the MANBA gene, which encodes the ß-mannosidase, can lead to the lysosomal storage disease ß-mannosidosis, as well as nystagmus, an eye condition characterized by involuntary eye movements. Here, we present the first structures of a mammalian ß-mannosidase in both the apo- and mannose-bound forms. The structure is similar to previously determined ß-mannosidase structures with regard to domain organization and fold, however, there are important differences that underlie substrate specificity between species. Additionally, in contrast to most other ligand-bound ß-mannosidases from bacterial and fungal sources where bound sugars were in a boat-like conformation, we find the mannose in the chair conformation. Evaluation of known disease mutations in the MANBA gene provides insight into their impact on disease phenotypes. Together, these results will be important for the design of therapeutics for treating diseases caused by ß-mannosidase deficiency. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 6DDT and 6DDU.

Sound abnormally stimulates the vestibular system in canal dehiscence syndrome by generating pathological fluid-mechanical waves.

Individuals suffering from Tullio phenomena experience dizziness, vertigo, and reflexive eye movements (nystagmus) when exposed to seemingly benign acoustic stimuli. The most common cause is a defect in the bone enclosing the vestibular semicircular canals of the inner ear. Surgical repair often corrects the problem, but the precise mechanisms underlying Tullio phenomenon are not known. In the present work we quantified the phenomenon in an animal model of the condition by recording fluid motion in the semicircular canals and neural activity evoked by auditory-frequency stimulation. Results demonstrate short-latency phase-locked afferent neural responses, slowly developing sustained changes in neural discharge rate, and nonlinear fluid pumping in the affected semicircular canal. Experimental data compare favorably to predictions of a nonlinear computational model. Results identify the biophysical origin of Tullio phenomenon in pathological sound-evoked fluid-mechanical waves in the inner ear. Sound energy entering the inner ear at the oval window excites fluid motion at the location of the defect, giving rise to traveling waves that subsequently excite mechano-electrical transduction in the vestibular sensory organs by vibration and nonlinear fluid pumping.

Familial congenital cataract, coloboma, and nystagmus phenotype with variable expression caused by mutation in PAX6 in a South African family.

Purpose: To report on a clinical and genetic investigation of a large, multigenerational South African family of mixed ancestry with autosomal dominant congenital cataracts, coloboma, and nystagmus. Methods: Ophthalmic examination was performed in 27 individuals from the same admixed South African family. DNA was sampled from either peripheral blood or buccal swabs in all 27 individuals, and whole genome sequencing was performed in six individuals. Sanger sequencing was used to validate the probable mutation in the remaining family members. Results: Twenty-seven family members with 19 affected individuals were included in the study. The predominant phenotype, with highly variable expression, was congenital cataract (14 individuals), posterior segment coloboma (17 individuals), and nystagmus (18 individuals). Other features present included high myopia, microcornea, and strabismus. An R208W mutation in PAX6 (dbSNP rs757259413; HGMD CM930572; NM_000280.3:c.622G>A; NP_000271.1:p.Arg208Trp) was identified as being the most probable pathogenic mutation. Cosegregation of the mutation with the phenotype was confirmed in all 27 family members. Conclusions: PAX6 is a highly conserved gene crucial for normal oculogenesis, and although mutations within the gene may cause an array of ocular developmental abnormalities, most are associated with aniridia and aniridia-related ocular defects. The observation that PAX6 aniridia phenotypes are largely associated with nonsense mutations and milder non-aniridia phenotypes with missense mutations suggested that there may be specific genotype-phenotype correlations for the gene. The R208W mutation in PAX6 identified in this family challenges this theory as it has previously been reported in three unrelated families and is associated with aniridia and non-aniridia phenotypes across the four families. PAX6 with its wide phenotypic associations and highly variable expression should be considered a candidate gene in the diagnostic screen for any ocular developmental abnormality.