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Objective: Gentamicin is a widely used aminoglycoside with ototoxicity as a known adverse effect. Because of the difficulty in clinical recognition, the prevalence of gentamicin ototoxicity in practice is thought to be higher than reported. This study aimed to prospectively assess the effect of gentamicin on vestibular function and whether ototoxicity is underrecognized., Study Design: Single-center, prospective, nonblinded trial., Setting: Inpatient tertiary hospital setting followed by vestibular outpatient clinic review., Patients: Forty-eight patients undergoing a urologic procedure were recruited, with 24 and 17 patients having one or two follow-up tests, respectively, after initial gentamicin administration., Interventions: Single dose of gentamicin during a urologic procedure., Main Outcome Measures: Gains for the vestibuloocular reflex (VOR) were measured using the video head impulse test before receiving gentamicin and at two other timepoints after gentamicin. The gains in VOR were then compared with previous testing sessions to determine if there was a deterioration after gentamicin use., Results: Before receiving gentamicin, the gains for horizontal VOR were measured for 48 patients. The gains were measured a second time for 24 patients at varying durations postgentamicin (1-56 d) and a third time for 17 patients (14-152 d) postgentamicin. The mean VOR gain for Timepoints 1, 2, and 3 were 0.72 ± 0.13, 0.75 ± 0.16, and 0.79 ± 0.18, respectively. Linear-mixed model with repeated-measure analysis revealed no significant difference in VOR gain between Timepoints 1 and 2 ( p = 0.19)., Conclusion: There was no significant effect observed on mean VOR gain decrement after a single dose of gentamicin., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Background and Purpose: A crossover, double-blinded randomized controlled trial to investigate once-daily incremental vestibulo-ocular reflex (VOR) adaptation (IVA) training over 2 years in people with stable and chronic peripheral vestibular hypofunction., Methods: Twenty-one patients with peripheral vestibular hypofunction were randomly assigned to intervention-then-control (n = 12) or control-then-intervention (n = 9) groups. The task consisted of either x1 (control) or IVA training, once daily every day for 15 minutes over 6-months, followed by a 6-month washout, then repeated for arm 2 of the crossover. Primary outcome: vestibulo-ocular reflex gain. Secondary outcomes: compensatory saccades, dynamic visual acuity, static balance, gait, and subjective symptoms. Multiple imputation was used for missing data. Between-group differences were analyzed using a linear mixed model with repeated measures., Results: On average patients trained once daily 4 days per week. IVA training resulted in significantly larger VOR gain increase (active: 20.6% ± 12.08%, P = 0.006; passive: 30.6% ± 25.45%, P = 0.016) compared with x1 training (active: -2.4% ± 12.88%, P = 0.99; passive: -0.6% ± 15.31%, P = 0.68) (P < 0.001). The increased IVA gain did not significantly reduce with approximately 27% persisting over the washout period. x1 training resulted in greater reduction of compensatory saccade latency (P = 0.04) and increase in amplitude (P = 0.02) compared with IVA training. There was no difference between groups in gait and balance measures; however, only the IVA group had improved total Dizziness Handicap Inventory (P = 0.006)., Discussion and Conclusions: Our results suggest IVA improves VOR gain and reduces perception of disability more than conventional x1 training. We suggest at least 4 weeks of once-daily 4 days-per-week IVA training should be part of a comprehensive vestibular rehabilitation program.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A356)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Academy of Neurologic Physical Therapy, APTA.)

One component of vestibular rehabilitation in patients with vestibulo-ocular reflex (VOR) hypofunction is gaze-stabilizing exercises that seek to increase (adapt) the VOR response. These prescribed home-based exercises are performed by the patient and thus their use/training is inherently variable. We sought to determine whether this variability affected VOR adaptation in ten healthy controls (× 2 training only) and ten patients with unilateral vestibular hypofunction (× 1 and × 2 training). During × 1 training, patients actively (self-generated, predictable) move their head sinusoidally while viewing a stationary fixation target; for × 2 training, they moved their outstretched hand anti-phase with their head rotation while attempting to view a handheld target. We defined the latter as manual × 2 training because the subject manually controls the target. In this study, head rotation frequency during training incrementally increased 0.5-2 Hz over 20 min. Active and passive (imposed, unpredictable) sinusoidal (1.3-Hz rotations) and head impulse VOR gains were measured before and after training. We show that for controls, manual × 2 training resulted in significant sinusoidal and impulse VOR adaptation of ~ 6 % and ~ 3 %, respectively, though this was ~two-thirds lower than increases after computer-controlled × 2 training (non-variable) reported in a prior study. In contrast, for patients, there was an increase in impulse but not sinusoidal VOR response after a single session of manual × 2 training. Patients had more than double the variability in VOR demand during manual × 2 training compared to controls, which could explain why adaptation was not significant in patients. Our data suggest that the clinical × 1 gaze-stabilizing exercise is a weak stimulus for VOR adaptation.

Background and Purpose: This was a double-blinded randomized controlled study to investigate the effects of once-daily incremental vestibulo-ocular reflex (VOR) training over 1 week in people with chronic peripheral vestibular hypofunction., Methods: A total of 24 patients with peripheral vestibular hypofunction were randomly assigned to intervention (n = 13) or control (n = 11) groups. Training consisted of either x1 (control) or incremental VOR adaptation exercises, delivered once daily for 15 minutes over 4 days in 1 week. Primary outcome: VOR gain with video-oculography. Secondary outcomes: Compensatory saccades measured using scleral search coils, dynamic visual acuity, static balance, gait, and subjective symptoms. Between-group differences were analyzed with a linear mixed-model with repeated measures., Results: There was a difference in the VOR gain increase between groups (P < 0.05). The incremental training group gain increased during active (13.4% ± 16.3%) and passive (12.1% ± 19.9%) head impulse testing (P < 0.02), whereas it did not for the control group (P = 0.59). The control group had reduced compensatory saccade latency (P < 0.02). Both groups had similarly improved dynamic visual acuity scores (P < 0.05). Both groups had improved dynamic gait index scores (P < 0.002); however, only the incremental group had improved scores for the 2 walks involving head oscillations at approximately 2 Hz (horizontal: P < 0.05; vertical: P < 0.02), increased gait speed (P < 0.02), and step length (P < 0.01) during normal gait, and improved total Dizziness Handicap Inventory (P < 0.05)., Conclusions: Our results suggest incremental VOR adaptation significantly improves gain, gait with head rotation, balance during gait, and symptoms in patients with chronic peripheral vestibular hypofunction more so than conventional x1 gaze-stabilizing exercises.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A336)., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Academy of Neurologic Physical Therapy, APTA.)

Background and Purpose: Traditional vestibular rehabilitation therapies are effective in reducing vestibular hypofunction symptoms, but changes to the vestibulo-ocular reflex (VOR) are minimal. This controlled case report describes an increase in VOR after 6 months of incremental VOR adaptation (IVA) training in a person with chronic unilateral vestibular hypofunction., Case Description: The participant was a 58-year-old female with a confirmed (Neurologist P.D.C.) left vestibular lesion stable for 2 years prior to entering a clinical trial examining the effects of daily IVA training. She was evaluated monthly for self-reported symptoms (dizziness handicap inventory), VOR function (video head impulse test), and VOR behavior (Dynamic Visual Acuity test). Intervention consisted of 6 months of 15 minutes per day unassisted training using the IVA training regime with a device developed in our laboratory. The take-home device enables the VOR response to gradually normalize on the ipsilesional side via visual-vestibular mismatch training. The intervention was followed by a 6-month wash-out and 3-month control period. The control condition used the same training device set to function like standard VOR training indistinguishable to the participant., Outcomes: After the intervention, ipsilesional VOR function improved substantially. The VOR adapted both via a 52% increase in slow-phase response and via 43% earlier onset compensatory saccades for passive head movements. In addition, the participant reported fewer symptoms and increased participation in sports and daily activities., Discussion: Here, a participant with chronic vestibular hypofunction showing improved oculomotor performance atypical for traditional vestibular rehabilitation therapies, subsequent to using the newly developed IVA technique, is presented. It is the first time to our knowledge an improvement of this magnitude has been demonstrated as well as sustained over an extended period of time., (© 2019 American Physical Therapy Association.)

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG) exp ] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG) 11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Genetic testing strategies such as next-generation sequencing (NGS) panels and whole genome sequencing (WGS) can be applied to the hereditary cerebellar ataxias (HCAs), but their exact role in the diagnostic pathway is unclear. We aim to determine the yield from genetic testing strategies and the genetic and phenotypic spectrum of HCA in Australia by analysing real-world data. We performed a retrospective review on 87 HCA cases referred to the Neurogenetics Clinic at the Royal North Shore Hospital, Sydney, Australia. Probands underwent triplet repeat expansion testing; those that tested negative had NGS-targeted panels and WGS testing when available. In our sample, 58.6% were male (51/87), with an average age at onset of 37.1 years. Individuals with sequencing variants had a prolonged duration of illness compared to those with a triplet repeat expansion. The detection rate in probands for routine repeat expansion panels was 13.8% (11/80). NGS-targeted panels yielded a further 11 individuals (11/32, 34.4%), with WGS yielding 1 more diagnosis (1/3, 33.3%). NGS panels and WGS improved the overall diagnostic rate to 28.8% (23/80) in 14 known HCA loci. The genetic findings included novel variants in ANO10, CACNA1A, PRKCG and SPG7. Our findings highlight the genetic heterogeneity of HCAs and support the use of NGS approaches for individuals who were negative on repeat expansion testing. In comparison to repeat disorders, individuals with sequencing variants may have a prolonged duration of illness, consistent with slower progression of disease.

Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Although cerebellar dysfunction has known effects on motor function in Friedreich ataxia (FRDA), it remains unclear the extent to which the reprogramming of eye movements (saccades) and inhibition of well-learned automatic responses are similarly compromised in affected individuals. Here we examined saccade reprogramming to assess the ability of people with FRDA to respond toward unexpected changes in either the amplitude or direction of an "oddball" target. Thirteen individuals with genetically confirmed FRDA and 12 age-matched controls participated in the study. The saccade reprogramming paradigm was used to examine the effect of an unpredictable "oddball" target on saccade latencies and accuracy when compared to a well-learned sequence of reciprocating movements. Horizontal eye movements were recorded using a scleral search coil eye tracking technique. The results showed a proportionally greater increase in latencies for reprogrammed saccades toward an oddball-direction target in the FRDA group when compared to controls. The FRDA group were also less accurate in primary saccade gain (i.e. ratio of saccade amplitude to target amplitude) when reprogramming saccades toward an unexpected change in direction. No significant group differences were found on any of the oddball-amplitude targets. Significant correlations were revealed between latency and disease severity as measured by the Friedreich Ataxia Rating Scale. These findings provide further support to the view that cognitive changes in FRDA may arise from disruption of cerebellar connections to cortical structures., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Inferior alveolar nerve blocks are commonly performed for dental anaesthesia. The procedure is generally safe with a low rate of complications. We report a patient with a reproducible, delayed-onset sensory deficit associated with contrast-enhancing lesions in the trigeminal nerve, pons and medulla following inferior alveolar nerve local anaesthesia. We propose that this previously undescribed condition is a form of Type IV hypersensitivity reaction., (Copyright © 2013. Published by Elsevier Ltd.)

Murine typhus (MT) occurs worldwide, but, in Australia, is only regularly diagnosed in south-west Western Australia. Meningoencephalitis is an uncommon complication of MT, often accompanied by rash or systemic involvement. We report a case of MT presenting exclusively with meningoencephalitis, raised intracranial pressure, papilloedema and bilateral 6th cranial nerve palsies. MT should be considered in patients with "aseptic" meningitis or meningoencephalitis, even in the absence of other typical features of a typhus-like illness.

The head impulse test can be used to measure peripheral vestibular function of all six semicircular canals. Traditionally, vertical canal function is measured by rotating the head from a starting neutral position (forward facing) about a diagonal plane that bisects the sagittal and coronal planes. These types of head rotations elicit eye movements with large vertical and torsional (about the line of sight) angular velocity components. Three-dimensional (3D: horizontal, vertical and torsional) eye measurement techniques are needed to measure these velocity components. We wanted to determine whether 2D measurements coupled to a modified head impulse test are sufficient to measure function of all six canals. In this study we measured individual canal function in patients (n=5) with peripheral unilateral hypofunction and control subjects (n=4) using the traditional head impulse test and the 'gold standard' 3D (dual-coil) scleral search coil technique. We compared these results with those from our 2D modified head impulse test using the 2D coil technique (single-coil). We show that both techniques detect similar levels of asymmetrical function in patients and are equally accurate in isolating canals with hypofunction. We conclude that 2D eye measurement techniques, such as video pupil-tracking, can be used to test all six canals.

Friedreich ataxia (FRDA) is the most common genetic cause of ataxia with a prevalence of approximately 1 in 29,000. Ocular motor abnormalities are common in FRDA and include fixation instability, saccadic dysmetria, and vestibular dysfunction. It has not yet been determined whether aspects of spatial attention, which are closely coupled to eye movements, are similarly compromised in FRDA. This study examined attentional engagement and disengagement of eye movements in FRDA using a gap overlap task. Thirteen individuals with genetically confirmed FRDA and 12 age-matched unaffected controls participated in the experiment. The gap overlap paradigm was used to examine the effect of early (gap condition), simultaneous (null condition), or late (overlap condition) removal of a central fixation on saccadic latency to a peripheral target stimulus. Although the FRDA group showed a larger gap effect (i.e., difference in saccadic latencies between the overlap and gap condition), these participants demonstrated a greater difference in latencies in the overlap relative to the null condition, suggestive of deficits within the disengagement process of attentional orienting. We propose a role for the cerebellum in these deficits in the disengagement of spatial attention based on evidence of cerebellar connectivity with regions involved in exogenous shifts of attention. The significant correlations between saccadic latency and disease severity as measured by the Friedreich Ataxia Rating Scale further support the proposal that saccadic latency might be useful as a surrogate marker of disease severity and progression in future clinical trials in FRDA.

Friedreich ataxia (FRDA), the commonest of the inherited ataxias, is a multisystem neurodegenerative condition that affects ocular motor function. We assessed eye movement abnormalities in 20 individuals with genetically confirmed FRDA and compared these results to clinical measures. All subjects were assessed with infrared oculography. Fifteen individuals underwent a full protocol of eye movement recordings. Ten subjects were analysed using two-dimensional scleral coil equipment and five using three-dimensional scleral coil recording equipment. We also recorded visual quality of life, Sloan low contrast letter acuity and Friedreich Ataxia Rating Scale scores to compare to the visual measures. Whilst saccadic velocity was essentially normal, saccadic latency was prolonged. The latency correlated with clinical measures of disease severity, including the scores for the Friedreich Ataxia Rating Scale and the Sloan low contrast letter acuity tests. Fixation abnormalities consisting of square wave jerks and ocular flutter were common, and included rare examples of vertical square wave jerks. Vestibular abnormalities were also evident in the group, with markedly reduced vestibulo-ocular reflex gain and prolonged latency. The range of eye movement abnormalities suggest that neurological dysfunction in FRDA includes brainstem, cortical and vestibular pathways. Severe vestibulopathy with essentially normal saccadic velocity are hallmarks of FRDA and differentiate it from a number of the dominant spinocerebellar ataxias. The correlation of saccadic latency with FARS score raises the possibility of its use as a biomarker for FRDA clinical trials.

Objective: Two recently described tests of the vestibular system, vestibular evoked myogenic potentials (VEMPs) and ocular vestibular evoked myogenic potentials (OVEMPs), test the descending and ascending vestibular brainstem pathways, respectively. We describe a case of a patient in whom these investigations localised the lesion and suggested its nature., Methods: VEMPs (to clicks and short duration galvanic stimulation) and OVEMPs (to clicks) were recorded., Results: Click- and galvanic-evoked VEMPs were delayed on the left side (by approximately 5-6 ms), and click-evoked OVEMPs were similarly delayed (by approximately 4 ms) following left-sided stimulation. Repeat testing 21 months later showed partial resolution., Conclusions: The observed delays in evoked potentials suggested a demyelinating lesion. Furthermore, the similarity in delayed responses to neck and extraocular muscles was suggestive of a lesion at the root entry zone of the vestibulocochlear nerve., Significance: VEMPs and OVEMPS may thus provide information about the location and nature of lesions affecting central vestibular pathways.

Purpose: As a normal subject looks from far to near, Listing's plane rotates temporally in each eye. Since Listing's plane relates to the control of torsional eye position, mostly by the oblique eye muscles, the current study was conducted to test the hypothesis that a patient with isolated superior oblique palsy would have a problem controlling Listing's plane., Method: Using the three-dimensional scleral search coil technique, binocular Listing's plane was measured in four patients with congenital and in four patients with acquired unilateral superior oblique palsy during far- (94 cm) and near- (15 cm) viewing. The results were compared to previously published Listing's plane data collected under exactly the same conditions from 10 normal subjects., Results: In patients with unilateral superior oblique palsy, either congenital or acquired, Listing's plane in the normal eye rotated temporally on near-viewing, as in normal subjects, while in the paretic eye it failed to do so. In patients with acquired superior oblique palsy, Listing's plane was already rotated temporally during far-viewing and failed to rotate any farther on near-viewing, whereas in patients with congenital superior oblique palsy Listing's plane in the paretic eye was oriented normally during far-viewing and failed to rotate any farther on near-viewing., Conclusions: These results suggest that the superior oblique muscle, at least in part, is responsible for the temporal rotation of Listing's plane that occurs in normal subjects on convergence., (Copyright Association for Research in Vision and Ophthalmology)

The authors report the unique case of a patient with a thoracic spinal dural arteriovenous fistula (DAVF) causing remote brainstem symptoms of positional vomiting and minimal vertigo. Magnetic resonance (MR) imaging of the brain demonstrated high signal abnormality in the medulla, presumably related to venous hypertension, and spinal MR imaging revealed markedly dilated veins along the dorsal aspect of the cord. Spinal angiography confirmed the presence of a thoracic spinal DAVF. Disconnection of the DAVF from the spine resulted in a marked improvement in symptoms and resolution of the preoperative MR imaging-documented abnormalities. The authors highlight the rare syndrome of positional vomiting as a brainstem symptom and conclude that spinal DAVFs should be considered in the differential diagnosis of high signal MR imaging abnormalities localized to the brainstem.

The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of approximately 2000 degrees /s(2 )and amplitude of approximately 20 degrees. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4 degrees during far viewing (94 cm) and 25 degrees during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began approximately 40 ms after the start of head rotation, was 10+/-6 degrees /s (mean +/- SD). This change in torsional eye velocity resulted in a 2.4+/-1.5 degrees axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16+/-6 degrees /s (mean +/- SD) and resulted in a 4.1+/-1.4 degrees axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing's plane. This tilt was higher than predicted by the one-quarter rule. The translational acceleration component of the pitch head rotation measured 0.5 g and may have contributed to the increased torsional component observed during near viewing. Our data show that vergence-mediated eye movements obey a VOR/Listing's Law compromise strategy independent of the initial eye position.

Objective: To identify patients with superior semicircular canal dehiscence and apparent conductive hearing loss and to define the cause of the air-bone gap., Study Design: Prospective study of patients with superior canal dehiscence. SETTING Tertiary referral center., Patients: Vestibular and/or auditory findings indicative of canal dehiscence and demonstration of superior canal dehiscence on computed tomography of the temporal bone., Intervention: Vestibular-evoked myogenic potentials, three-dimensional eye movement recordings, and surgical resurfacing of the superior canal., Outcome Measure: Association of superior canal dehiscence with an air-bone gap on audiometry., Results: Four patients with dehiscence of bone overlying the superior canal were found to have air-bone gaps in the affected ears that were greatest at lower frequencies and averaged 24 +/- 7 dB over the frequency range of 250 to 4,000 Hz. Three of these patients had undergone stapedectomy before the identification of superior canal dehiscence. The air-bone gap was unchanged postoperatively. Each patient had an intact vestibular-evoked myogenic potential (VEMP) response from the affected ear, a finding that would not have been expected based on a middle ear cause of conductive hearing loss. One patient underwent resurfacing of the superior canal through a middle fossa approach. Postoperatively, his vestibular symptoms were relieved, and his air conduction thresholds were improved by 20 dB., Conclusions: Superior canal dehiscence can result in apparent conductive hearing loss. The third mobile window created by the dehiscent superior canal results in dissipation of acoustic energy and is a cause of inner ear conductive hearing loss.

The 3-dimensional angular vestibulo-ocular reflexes (AVOR) elicited by rapid rotary head thrusts were studied in 17 subjects with unilateral Ménière's disease before and 2-10 weeks after treatment with intratympanic gentamicin and in 13 subjects after surgical unilateral vestibular destruction (SUVD). Each head thrust was in the horizontal plane or in either diagonal plane of the vertical semicircular canals, so that each head thrust effectively stimulated only one pair of canals. The AVOR gains (eye velocity/head velocity during the 30 ms before peak head velocity) for the head thrusts exciting each individual canal were averaged and taken as a measure of the function of that canal. Prior to intratympanic gentamicin, gains for head thrusts that excited canals on the affected side were 0.91 +/- 0.20 (horizontal canal, HC), 0.78 +/- 0.20 (anterior canal, AC), and 0.83 +/- 0.10 (posterior canal, PC). The asymmetries between these gain values and those for head thrusts that excited the contralateral canals were <2%. In contrast, caloric asymmetries averaged 40% +/- 32%. Intratympanic gentamicin resulted in decreased gains attributable to each canal on the treated side: 0.40 +/- 0.12 (HC), 0.35 +/- 0.14 (AC), 0.31 +/- 0.14 (PC) (p <0.01). However, the gains attributable to contralateral canals dropped only slightly, resulting in marked asymmetries between gains for excitation of ipsilateral canals versus their contralateral mates: HC: 34% +/- 12%, AC: 24% +/- 25%, and PC: 42% +/- 13%. There was no difference in the AVOR gain for excitation of the ipsilateral HC after gentamicin in patients who received a single intratympanic injection (0.39 +/- 0.11, n = 12) in comparison to those who received 2-3 injections (0.42 +/- 0.15, n = 5, p = 0.7). Gain decreases attributed to the gentamicin-treated HC and AC were not as severe as those observed after SUVD. This finding suggests that intratympanic gentamicin causes a partial vestibular lesion that may involve preservation of spontaneous discharge and/or rotational sensitivity of afferents.

Objectives: To compare 2 clinical tests of vestibular function, the head autorotation test (HART) and the head thrust test (HTT), and to determine why they give disparate results in patients with known unilateral vestibular deficiency (UVD) due to labyrinthectomy., Methods: We used scleral coils to measure the horizontal (yaw) vestibulo-ocular reflex (VOR) in 5 healthy human subjects and in 11 patients who underwent labyrinthectomy. We used 2 paradigms. Using HART, subjects visually fixated a target during self-generated, swept-frequency, sinusoidal, horizontal head rotations. Using HTT, patients fixated the target during horizontal head thrusts delivered randomly in direction and time., Results: In subjects without UVD, eye movements were almost perfectly compensatory for both paradigms. In subjects with UVD, VOR gain for ipsilesional head thrusts was low for both paradigms, but significantly (P<.001) higher (less abnormal) for HART (0.60 +/- 0.13) than for HTT (0.14 +/- 0.13). Contralesional gain was reduced for both, to 0.64 +/- 0.20 for HART and to 0.57 +/- 0.17 for HTT. Because ipsilesional and contralesional gains were not statistically different for HART (P =.69), comparison of VOR gains for half-cycle responses to the HART stimulus could not reliably identify the side of the known lesion. In contrast, HTT consistently identified the side of the lesion for all subjects with UVD. To investigate whether preprogramming contributes to the boost in VOR as measured by HART, we compared the gain and response delay of eye movements during actively self-generated and passively received head thrusts. For subjects without UVD, response delays were shorter for active (6 +/- 1 milliseconds) than for passive (12 +/- 1 milliseconds) HTT. For ipsilesional rotations of subjects with UVD, active HTT yielded a significantly higher gain (0.44 +/- 0.20) (P<.001) and a shorter delay (15 +/- 6 milliseconds) (P<.001) than did passive HTT (0.14 +/- 0.13 and 37 +/- 15 milliseconds, respectively). Contralesional test results revealed a similar performance boost for active head movements. Data are given as mean +/- SD., Conclusion: When comparison of half-cycle gains is used to identify the lesion side, self-generated predictable head movement paradigms, such as HART and active HTT, are less accurate than passive HTT in the characterization of UVD, in part because preprogramming can augment the VOR during voluntary head movements.

Patients with superior canal dehiscence (SCD) syndrome experience vertigo and oscillopsia in response to loud sounds and to stimuli that result in changes in middle ear or intracranial pressure. They may also experience hyperacusis to bone-conducted sounds. The evoked eye movements in this syndrome align with the plane of the dehiscent superior canal. The symptoms and signs can be understood in terms of the effect of the dehiscence in creation of a third mobile window into the inner ear. The SCD syndrome has been diagnosed in 28 patients who were examined in the neuro-otology clinics at the Johns Hopkins Medical Institutions from May 1995 through January 2001. The diagnosis is best established based upon the symptoms that are characteristic for the syndrome, the vertical-torsional eye movements evoked by sound or pressure stimuli noted on examination performed with Frenzel goggles, the lowered thresholds for responses to vestibular-evoked myogenic potentials, and CT imaging of the temporal bones.

In order to test the human angular vestibulo-ocular reflex in the dynamic range of normal head movements, we measured 3-dimensional compensatory eye-movement responses to low-amplitude (10-12 degrees), high-acceleration (3000-4000 degrees/s/s), passive, manually delivered head rotations (head "impulses") in the three planes of the semicircular canals in normal subjects, in subjects who had recovered from surgical unilateral vestibular deafferentation, and in patients after acute unilateral peripheral vestibulopathy, that is, from vestibular "neuritis." We found that canal-plane head impulses away from an intact semicircular canal, that is, toward a lesioned semicircular canal, invariably produce a vestibulo-ocular reflex with permanently low gain, typically less that 0.4 if the lesion is complete. These results are a necessary consequence of primary semicircular canal afferents being driven into inhibitory saturation by rapid angular accelerations. With practice, clinicians can learn to recognize the telltale compensatory saccades that patients with unilateral loss of semicircular canal function will make if asked to look at an earth-fixed target during head impulses in any one of the three semicircular canal planes.

Objective: To examine the concept of selective superior and inferior vestibular nerve involvement in vestibular neuritis by studying the distribution of semicircular canal (SCC) involvement in such patients., Background: Vestibular neuritis was traditionally thought to involve the superior and inferior vestibular nerves. Recent work suggests that in some patients, only the superior nerve is involved. So far there are no reported cases of selective involvement of the inferior vestibular nerve., Methods: The authors measured the vestibuloocular reflex from individual SCC at natural head accelerations using the head impulse test. The authors studied 33 patients with acute unilateral peripheral vestibulopathy, including 29 with classic vestibular neuritis and 4 with simultaneous ipsilateral hearing loss, 18 healthy subjects and 15 surgical unilateral vestibular deafferented patients., Results: In patients with preserved hearing, eight had deficits in all three SCC, suggesting involvement of the superior and inferior vestibular nerves. Twenty-one had a lateral SCC deficit or a combined lateral and anterior SCC deficit consistent with selective involvement of the superior vestibular nerve. Two patients with ipsilateral hearing loss had normal caloric responses and an isolated posterior SCC deficit on impulsive testing. The authors propose that these two patients had a selective loss of inferior vestibular nerve function., Conclusion: Vestibular neuritis can affect the superior and inferior vestibular nerves together or can selectively affect the superior vestibular nerve.

Patients with superior canal dehiscence (SCD) syndrome have vertigo and oscillopsia induced by loud noises and by stimuli that result in changes in middle ear or intracranial pressure. We recorded vestibular-evoked myogenic potentials (VEMP responses) in 10 patients with SCD syndrome. The diagnosis had been confirmed in each case by evoked eye movements and by high-resolution CT scans of the temporal bones that showed a dehiscence overlying the affected superior canal. For the 8 patients without prior middle ear disease, the VEMP threshold from the dehiscent ears measured 72 +/- 8 dB NHL (normal hearing level) whereas the threshold from normal control subjects was 96 +/- 5 dB NHL (p < 0.0001). The VEMP threshold measured from the contralateral ear in patients with unilateral dehiscence was 98 +/- 4 dB NHL (p > 0.9 with respect to normal controls). Two patients with apparent conductive hearing loss from middle ear disease, and SCD, had VEMP responses from the affected ears. In the absence of dehiscence, VEMP responses would not have been expected in the setting of conductive hearing loss. These findings confirm earlier studies demonstrating that patients with SCD syndrome have lowered VEMP thresholds. Conditions other than SCD syndrome may also lead to lowered VEMP thresholds. Rather than being based upon a single test, the diagnosis of SCD syndrome is best established when the characteristic symptoms, signs, VEMP response, and CT imaging all indicate SCD.

Background: The superior canal dehiscence (SCD) syndrome consists of sound- or pressure-induced nystagmus and vertigo caused by a defect in bone overlying the superior semicircular canal. The SCD syndrome is diagnosed based upon characteristic symptoms, signs, and findings on CT imaging of the temoral bones. However, SCD syndrome is often misdiagnosed as perilymphatic fistula (PLF), and the symptoms of sound- and pressure-induced vertigo are more commonly attributed to the vestibular utricle, rather than to the superior semicircular canal. This study explored the role of the superior canal and the utricle in the pathophysiology of SCD syndrome., Methods: Three-dimensional scleral search coils were used to record eye movements in 11 patients with SCD syndrome., Results: Ten patients developed nystagmus with upward torsional slow phases characteristic of superior canal activation when loud tones were presented to the affected ear or when the patients performed a Valsalva maneuver. Visual fixation led to a suppression of the nystagmus and the appearance of a sustained torsional deviation of the eyes. Two patients also had sound-evoked head movements in the same direction as the ocular slow phases. The response of the affected superior canal to rapid head rotations was tested in nine patients. The response was diminished in those with large (>/=5 mm) defects in the bone overlying the superior canal., Conclusions: The evoked eye movements in patients with SCD syndrome arise from the superior canal, not the utricle. The syndrome is recognized by the characteristic nystagmus evoked by tones or maneuvers that change middle ear or intracranial pressure. Examination for this nystagmus should be performed under conditions that prevent visual fixation.

Background: Susac syndrome is characterized by the triad of branch retinal arterial occlusions, encephalopathy and cochlear microangiopathy. The underlying process is believed to be a small vessel vasculitis causing microinfarcts in the retina, brain and cochlea., Methods: Analysis of two male and two female cases of Susac syndrome recognized in Australia., Results: In this series the epidemiology, mode of presentation, ophthalmologic features, neurologic and cochleo-vestibular features, radiologic characteristics, cerebrospinal fluid findings, therapeutic interventions, clinical course and outcome of Susac syndrome is examined. Key ophthalmologic differential diagnoses include systemic lupus erythematosis (SLE), Behçet's syndrome and other vasculitides such as sarcoidosis, tuberculosis, syphilis and lymphoma. Neuro-otologic features are most frequently misdiagnosed as multiple sclerosis., Conclusion: Susac syndrome, first described in 1979, is becoming an increasingly recognized condition. Early recognition of the syndrome is important because treatment with systemic immunosuppression may minimize permanent cognitive, audiologic and visual sequelae.

Hypothesis: The purpose of this study was to simulate an isolated directional preponderance (DP) on bithermal caloric testing by constructing a realistic neural network model. The simulation was designed to capture not only the characteristics of the nystagmus response to caloric stimulation but also the response to rotational stimulation in patients with an isolated caloric DP., Background: The nature of an isolated DP--that is, a DP in the absence of a significant spontaneous nystagmus or canal paresis--is outlined in the preceding article. In this article, the authors investigate the possible neural basis for an isolated caloric DP using the mathematic modeling technique of neural network simulation. Neural network models are typically abstract in nature; however, in this case the network was based on the known structure and function of the central vestibular system., Methods: The neural network model was based on the known neuroanatomy and neurophysiology of the horizontal vestibuloocular reflex pathway. A leftward-rightward asymmetric modification of the dynamic responses of simulated medial vestibular nucleus type IA neurons on one side, or of type 2 neurons on the other side, to peripheral input would generate an isolated caloric DP., Results: The values of DP and associated canal paresis produced by the network were within the same range as in the patient group. The network also predicted that the rotational DP would be lower than the caloric DP: between 2.5% and 56.9% of the caloric DP value. The actual rotational DP value was between 3% and 57% (average 41%) of the corresponding caloric DP value., Conclusions: An isolated caloric DP can be simulated by a neural network model by modifying the activity of model units that represent medial vestibular nucleus neurons. An asymmetric dynamic response by a gain-enhancement function of either type 1A neurons on one side or of type 2 neurons on the other was sufficient to produce an isolated caloric DP. Excitatory gain enhancement of type 2 neurons produced a smaller rotational DP than a similar modification of type 1 neurons. This result indicates a potential neural locus for the generation of an isolated DP in patients with vestibular disorders.

Objectives: To determine the clinical significance of an isolated directional preponderance (DP) on bithermal caloric testing. An isolated caloric DP was defined as a DP, calculated according to the standard Jongkees formula, of > or = 40%, with a spontaneous nystagmus (SN) in darkness of < or = 2 degrees/s and a canal paresis (unilateral weakness) of < or = 25%., Study Design: A retrospective analysis of all 15,542 bithermal caloric tests performed in the authors' department in the previous 10 years to identify all tests with an isolated DP of > or = 40%. This was followed by a review of the clinical data on the 144 patients identified with such a result and then by a telephone or postal follow-up study of these patients. The study group eventually comprised 114 patients; these were patients in whom a clinical diagnosis could be made at the time the caloric test was done, or who responded to requests for follow-up information. The 34 patients in whom a clinical diagnosis could not be made at the time of the caloric test, and who did not respond to requests for follow-up information, were excluded., Study Setting: A balance disorders clinic in a tertiary referral hospital., Intervention: All patients underwent standard bithermal caloric testing. Some of the patients also underwent rotational testing., Outcome Measures: A clinical diagnosis for the cause of the isolated DP, made either at the time of the caloric test or on the basis of information supplied at follow-up by the patient or by the referring physician., Results: Of 114 patients, 39 had benign paroxysmal positioning vertigo, 14 had Ménière's disease, and 5 had migrainous vertigo. Five patients had central nervous system (CNS) disorders, and this was clinically apparent at the time of the caloric test in 4, so that only 1 patient with an isolated DP developed evidence of a CNS disorder after the caloric test was done. In the other 54 patients, no definite diagnosis could be made, but 41 of these 54 were either completely well or much better at follow-up., Conclusions: An isolated DP on caloric testing is usually a transient, benign disorder. About half the patients with an isolated DP have either Ménière's disease or benign paroxysmal positioning vertigo; in most of the other half, no definite diagnosis is made but most of these patients will do well. Only approximately 5% have a CNS lesion and in almost all this is apparent at the time the caloric test is done. In a relapsing-remitting peripheral vestibular disorder such as benign paroxysmal positioning vertigo or Ménière's disease, the mechanism of an isolated DP could be enhanced dynamic gain of ipsilesional medial vestibular nucleus neurons, perhaps as a result of intermittent hyperfunction of primary semicircular canal vestibular afferents. The authors postulate that an isolated DP reflects a gain asymmetry between neurons in the medial vestibular nucleus on either side, caused either by increased sensitivity on one side or by reduced sensitivity on the other, perhaps as an adaptive change in response to abnormal input. In an accompanying article, the authors implement a realistic neural network model in which it is possible to simulate an isolated DP by adjusting the dynamic sensitivity of type 1 medial vestibular nucleus neurons on one side or of type 2 medial vestibular nucleus neurons on the other.

A patient with a postoperative fistula of the left posterior semicircular canal is presented. Negative pressure in the external ear canal produced upbeat-torsional nystagmus, which was recorded in three dimensions using binocular scleral search coils. The nystagmus was conjugate, without skew deviation, and its trajectory corresponded to the anatomic axis of the left posterior canal. The current study helps validate Ewald's first law in humans: the axis of nystagmus should match the anatomic axis of the semicircular canal that generated it. This law is clinically useful in diagnosing pathology of the vestibular end-organ, such as benign paroxysmal positional vertigo or the superior semicircular canal dehiscence syndrome.

We measured the vestibulo-ocular reflex (VOR) during head impulses in a patient with right-sided internuclear ophthalmoplegia. Head impulses are rapid, passive, high-acceleration, low-amplitude head rotations in the direction of a particular semicircular canal (SCC). Adduction of the right eye was abnormally slow during right lateral SCC head impulses. The VOR during left posterior SCC impulses was severely deficient in both eyes, but the VOR during left anterior SCC impulses was only slightly deficient. We suggest that the vertical vestibulo-ocular pathways in humans are connected in SCC-plane coordinates, not the traditional roll and pitch coordinates, and that anterior SCC signals do not travel exclusively in the medial longitudinal fasciculus.

We studied the human vestibulo-ocular reflex (VOR) in response to head 'impulses': brief, unpredictable, passive, high-acceleration (up to 4000 degrees/s2), low-amplitude (20-30 degrees) head rotations. We delivered the head impulses approximately in the plane of the semicircular canal (SCC) being tested. To test the anterior and posterior SCCs, the head impulses were delivered in a diagonal plane, midway between the frontal (roll) and sagittal (pitch) planes. We recorded head and eye position in three dimensions with scleral search coils in nine normal subjects, seven patients following unilateral surgical vestibular neurectomy and three patients following unilateral posterior SCC occlusion. In the post-surgical patients we demonstrated a severe, permanent VOR gain deficit (0.2-0.3) for head impulses directed toward any single non-functioning SCC. The sensitivity of the test depends on the physiological properties of primary vestibular afferents, and its specificity depends on the anatomical orientation of the SCCs. The diagonal head impulse is the first test of individual vertical SCC function in humans, and together with the horizontal head impulse, forms a comprehensive battery of SCC-plane tests. These canal-plane impulses could be useful in evaluating patients with vertigo or other vestibular disorders.

Three cases are reported of the pseudotumour cerebri syndrome-that is, intracranial hypertension without mass lesion or enlarged ventricles, due to cryptococcal meningitis. In these patients the papilloedema was successfully treated with optic nerve sheath decompression, and the intracranial hypertension with lumboperitoneal CSF shunting. These cases support the concept that pseudotumour cerebri is a syndrome of intracranial hypertension that can be due to any disorder producing obstruction of the CSF pathways at the level of the arachnoid villi. This concept is important because it directs therapy to normalise the intracranial pressure and preserve vision.

A 29-year-old male underwent allogeneic bone marrow transplantation for progressive multiple myeloma. His post-transplant course was complicated by severe chronic pulmonary graft-versus-host disease (GVHD) resistant to cyclosporin A, corticosteroids and azathioprine. The introduction of thalidomide resulted in a dramatic improvement in his lung function which has been maintained even after cessation of thalidomide. He remains well 40 months after transplantation.

A patient was seen with secondary cluster headache whose acute pain responded promptly to sumatriptan. The headaches started after injury to the vertebral artery. This finding provides clinical affirmation of the existence of the trigeminal/cervical nuclear overlap that is central to this condition.

The normal horizontal vestibulo-ocular reflex (HVOR) is largely generated by simultaneous stimulation of the two horizontal semicircular canals (HSCCs). To determine the dynamics of the HVOR when it is generated by only one HSCC, compensatory eye movements in response to a novel vestibular stimulus were measured using magnetic search coils. The vestibular stimulus consisted of low-amplitude, high-acceleration, passive, unpredictable, horizontal rotations of the head with respect to the trunk. While these so called head "impuses" had amplitudes of only 15-20 degrees with peak velocities up to 250 deg/s, they had peak accelerations up to 3000 deg/s/s. Fourteen humans were studied in this way before and after therapeutic unilateral vestibular neurectomy; 10 were studied 1 week or 1 year afterwards; 4 were studied 1 week and 1 year afterwards. The results from these 14 patients were compared with the results from 30 normal control subjects and with the results from one subject with absent vestibular function following bilateral vestibular neurectomy. Compensatory eye rotation in normal subjects closely mirrored head rotation. In contrast there was no compensatory eye rotation in the first 170 ms after the onset of head rotation in the subject without vestibular function. Before unilateral vestibular neurectomy all the patients' eye movement responses were within the normal control range. One week after unilateral vestibular neurectomy however there was a asymmetrical bilateral HVOR deficit. The asymmetry was much more profound than has been shown in any previous studies. The HVOR generated in response to head impulses directed away from the intact side largely by ampullofugal disfacilitation from the single intact HSCC (ignoring for the moment the small contribution to the HVOR from stimulation of the vertical SCCs), was severely deficient with an average gain (eye velocity/head velocity) of 0.25 at 122.5 deg/sec head velocity (normal gain = 0.94 +/- 0.08). In contrast the HVOR generated in response to head impulses directed toward the intact side, largely by ampullopetal excitation from the single intact HSCC, was only mildly (but nonetheless significantly) deficient, with an average gain of 0.80 at 122.5 deg/sec head velocity. At these accelerations there was no significant improvement in the average HVOR velocity gain in either direction over the following year. These results indicate that ampullopetal excitation from one HSCC can, even in the absence of ampullofugal disfacilitation from the opposite HSCC, generate a near normal HVOR in response to high-acceleration stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine the relative contributions of ampullofugal (AF) and ampullopetal (AP) stimulation of the horizontal semicircular canal (HSCC) to the horizontal vestibulo-ocular reflex (HVOR), 12 patients were studied 1 year after total unilateral vestibular deafferentation (UVD). Compensatory eye movement responses to impulses of horizontal head rotation were studied using magnetic search coils. The head impulses were rapid (up to 3000 deg/sec/sec) passive, unpredictable, step displacements of horizontal angular head position with respect to the trunk. The results from these 12 patients were compared with results from 30 normal subjects. An HVOR deficit was found to each side. The HVOR in response to head impulses toward the deafferented side, a response generated exclusively by ampullofugal stimulation of the single functioning HSCC, was severely deficient with an average gain of 0.25; the HVOR in response to head impulses toward the intact side, a response generated exclusively by ampullopetal stimulation of the single functioning HSCC, was mildly but significantly deficient compared with normal subjects. These results show that rapid, unpredictable head movements, unlike slow, predictable head movements, do demonstrate the AP-AF HVOR asymmetry, which could be expected from consideration of the behavior of single vestibular afferent neurons, an asymmetry that is expressed by Ewald's 2nd Law.