Signs Of Vestibular Dysfunction Research Articles

Evaluating diagnostic and management agreement between physiotherapists and ear, nose and throat specialist in a primary contact physiotherapy-led vestibular clinic: A prospective blinded inter-rater agreement pilot study

BackgroundDizziness and vertigo are common referrals to Ear Nose Throat (ENT) outpatient services however these services have long waitlists for assessment. Primary contact physiotherapy-led vestibular clinics are recognized as improving access to care. This pilot study investigated agreement between physiotherapists and an ENT medical practitioner for diagnostic and management decisions in patients attending a primary contact physiotherapy-led vestibular clinic.MethodsProspective blinded inter-rater agreement study undertaken in an ENT primary contact physiotherapy-led vestibular clinic. Participants were adults referred to ENT from general practitioners, triaged (Category 2 or 3) to the primary contact physiotherapy-led vestibular clinic with clinical symptoms consistent with vestibular disorder. Primary outcome measures included agreement of diagnoses and management decisions made by an ENT medical practitioner and Physiotherapist based on a vestibular physiotherapy assessment. Adverse events were reviewed 11 months post data collection. Gwet’s first order agreement co-efficient (AC1) calculated inter-rater reliability between physiotherapy and ENT.ResultsFifty-one participants were recruited consecutively from the primary contact physiotherapy-led vestibular clinic. Physiotherapy and ENT had a substantial agreement (AC1 0.613) on diagnosis. AC1 between physiotherapy and ENT for recommending Magnetic resonance imaging (0.810) and computerized tomography (0.935) both indicated near perfect agreement. There was moderate to near-perfect agreement regarding management recommendations between physiotherapy and ENT. Substantial agreement (AC1 0.720) was found for recommendations for ENT input, near perfect agreement (AC1 0.933) for neurology input and moderate agreement (AC1 0.574) for physiotherapy input. There were no adverse events from physiotherapist’s management decision, based on final recommendations undertaken 11-months post data collection.ConclusionsPhysiotherapists and ENT medical practitioner made comparable diagnostic and management decisions, based on physiotherapy and audiology hearing assessment, for adults with signs of vestibular dysfunction, within an ENT primary contact physiotherapy-led vestibular clinic. This study provides support for this type of Physiotherapy-led service in managing patients referred to an ENT service with vestibular dysfunction.

Greater Disability Is Associated with Worse Vestibular and Compensatory Oculomotor Functions in People Living with Multiple Sclerosis.

Globally, there are nearly three million people living with multiple sclerosis (PLW-MS). Many PLW-MS experience vertigo and have signs of vestibular dysfunction, e.g., low vestibulo-ocular reflex (VOR) gains or the presence of compensatory saccades (CSs), on video head impulse testing (vHIT). We examined whether the vestibular function and compensatory oculomotor behaviors in PLW-MS differed based on the level of MS-related disability. The VOR gain, CS frequency and latency, and gaze position error (GPE) were calculated from the individual traces obtained during six-canal vHIT for 37 PLW-MS (mean age 53.4 ± 12.4 years-old, 28 females) with vertigo and/or an imbalance. The subjects were grouped by their Expanded Disability Status Scale (EDSS) scores: PLW-min-MS (EDSS = 1.0-2.5, n = 8), PLW-mild-MS (EDSS = 3.0-4.5, n = 23), and PLW-moderate-MS (EDSS = 5.0-6.0, n = 6). The between-group differences were assessed with Kruskal-Wallis tests. The VOR gains for most of the canals were higher for PLW-min-MS compared to PLW-mild- and mod-MS, respectively. CS occurred less often in PLW-min-MS versus PLW-mild- and mod-MS, respectively. No clear trend in CS latency was found. The GPE was often lower for PLW-min-MS compared to PLW-mild- and mod-MS, respectively. Thus, our data demonstrate that worse VOR and compensatory oculomotor functions are associated with a greater MS-related disability. PLW-MS may benefit from personalized vestibular physical therapy.

The Adaptation of Participation Scale Short Simplified Questionnaire into Indonesian Language and the Psychometric Properties in Individuals with Type 2 Diabetes Mellitus with Vestibular Dysfunction.

Background Type 2 diabetes mellitus (T2DM) has been reported to affect the vestibular system resulting in dizziness and vertigo complaints. This complication is known to disable the social participation. The Participation Scale Short Simplified (PSSS) has been developed to quantify the severity of social participation restrictions. The aim of this study was to translate and cross-culturally adapt the PSSS into Indonesian Bahasa (PSSS-Ina). The measurement properties of the translated version and the factors contributing to the severe participation restriction were determined. Methods The participants comprised 55 T2DM with vestibular dysfunction (VD) in the community center for diabetes mellitus in Central Java, Indonesia. The signs of VD were confirmed by head impulse test, Dix Hallpike Test, and supine roll test. The PSSS-Ina was administered twice with a four-week interval. The physical examination was also performed to identify the contributing factors. Results The test–retest reliability of the PSSS Indonesian Bahasa version (PSSS-Ina) between two measurement sessions was excellent (ICC of 0.93, p < 0.001, and 95% CI: 0.88–0.95). The correlation coefficient between two administrations was high (r = 0.88). Based on the demonstrated content validity, the values of the corrected item and total correlation were greater than 0.3. No floor and ceiling effects were observed. The good internal consistency was confirmed with Cronbach's alpha of 0.84. The factor analysis produced three factors of activity participation, social engagement, and work-related participation. The multiple logistic regression revealed that the balance performance of mCTSIB was the main factor contributing to the severe participation restriction reflected by the PSSS-Ina score. Conclusion The Indonesian version of the PSSS-Ina demonstrated excellent comprehensibility and reliability in individuals suffering T2DM with VD. This tool is therefore helpful in identifying the participation limitation in individuals with VD.

MAIN ISSUES OF CHILDREN'S INCIDENCE OF ACUTE OTITIS MEDIA AND PROSPECTS TO SOLVE THEM

The problem of acute otitis media in children is relevant because of the prevalence, social significance, possibility of rapid development of both life−threatening intracranial and intralabyrinthine, mastoid complications, as well as acute or prolonged dysfunction of adjacent cranial nerves, especially auditory, vestibular ones. In order to determine the frequency of various forms of acute otitis media, the nature and extent of its complications in children of different ages there was conducted a retrospective analysis of medical histories of patients treated at the City Clinical Hospital № 30 Kharkiv within 2015−2019. There was stated that the biggest group was composed by the patients with a purulent form of the disease, a slightly smaller number of patients had secretory and viral processes. But when analyzing the data over the years, of interest is the fact that during the period when the number of purulent forms decreased, the number of viral ones increased. Complications include mastoiditis, acute sensorineural hearing loss, cerebrospinal fluid and hypertension and intoxication syndromes. It is important that in acute purulent and viral otitis there is an intoxication syndrome along with the manifestations of acute sensorineural hearing loss. Signs of vestibular dysfunction in children can be disguised as symptoms of intoxication, they are much more difficult to detect. Considering the fact that the snail and the labyrinth are washed by the same liquid, it is logical to assume that in this situation the vestibular analyzer suffers together with the auditory one. Therefore, along with otoneurological research it is necessary to apply instrumental methods for establishment of latent disturbances of function of the vestibular analyzer. According to the research results it was concluded that a more detailed study of vestibular analyzer dysfunction in children with acute otitis media, as they are disguised as symptoms of intoxication. Key words: acute otitis media, frequency, complications, vestibular disorders, children.

O-01 Persistent postural-perceptual dizziness: clinical and neurophysiological study

Background Persistent postural-perceptual dizziness (PPPD) is a relatively new syndrome with diagnostic criteria being published in 2017. Aim of this study was to evaluate the clinical and neurophysiological characteristics of PPPD. Materials and methods This was a retrospective performed in the vertigo clinic of the University Hospital Center Zagreb, Croatia. The following data were extracted from the electronic hospital records: age, sex, the duration of symptoms, initial trigger event, results of the caloric testing, video head impulse test, ocular and cervical vestibular evoked myogenic potentials. Results 147 consecutive patients with dizziness were examined and 28 (19%) were diagnosed with PPPD. Most common initial event was vestibular neuritis in 39.3% of patients, followed by benign paroxysmal positional vertigo in 10.7% of patients. One patient had normal findings, one patient had signs of vestibular dysfunction on all of the tests, one had pathology demonstrated by vHIT only, seven patients had pathological VEMP, while five patients had vestibular dysfunction on both VEMP and vHIT. Neurophysiological evaluation results are presented in Table. All patients with unknown pathology who performed neurophysiological tests had normal calorics, while 3 out of 4 had vHIT abnormalities. Conclusion This study provides clinical and neurophysiological data on PPPD.

A Xenograft Model of Vestibular Schwannoma and Hearing Loss.

Microsurgical implantation of mouse merlin-deficient Schwann cells (MD-SC) into the cerebellopontine angle of immunodeficient rats will initiate tumor formation, hearing loss, and vestibular dysfunction. The progress in identifying effective drug therapies for treatment of Neurofibromatosis type II (NF2) is limited by the availability of animal models of VS that develop hearing loss and imbalance. A microsurgical technique for implanting MD-SCs onto the cochleovestibular nerve of rats was developed. Ten Rowett Nude rats were implanted with either ∼10 MD-SCs expressing luciferase (N = 5) or vehicle (N = 5). Rats received bioluminescence imaging, auditory brainstem response testing, and were observed for head tilt every 2 weeks after surgery, for a total of 6 weeks. Tumors were harvested and processed with hematoxylin & eosin staining and immunohistochemistry was performed for S100. Rats implanted with MD-SCs developed significantly higher tumor bioluminescence measurements and hearing threshold shifts at multiple frequencies by the 4th and 6th weeks post-implantation, compared with control rats. Rats implanted with MD-SCs also developed gross tumor. The tumor volume was significantly greater than nerve volumes obtained from rats in the control group. All rats with tumors developed a head tilt, while control rats had no signs of vestibular dysfunction. Tumors demonstrated histological features of schwannoma and express S100. Using this microsurgical technique, this xenograft rat model of VS develops tumors involving the cochleovestibular nerve, shifts in hearing thresholds, and vestibular dysfunction. This animal model can be used to investigate tumor-mediated hearing loss and perform preclinical drug studies for NF2.

Canine and feline vestibular syndrome

Signs of vestibular dysfunction (head tilt, asymmetric ataxia, spontaneous nystagmus, unilateral falling and rolling) are characteristic enough to be easily recognized without difficulty, even by inexperienced clinicians. Further differentiation between the peripheral (inner ear, vestibular nerve) and the central (vestibular nuclei, cerebellar peduncles, fastigial nucleus and flocculonodular lobe of the cerebellum) vestibular system should be based on a thorough history and an astute neurological examination. Affected animals should be reevaluated by serial neurological reexaminations to improve the accuracy of the initial assessment. Concomitant neurological signs, such as spastic hemiparesis or tetraparesis, proprioceptive déficits, other cranial nerve dysfunction and/or behavioral changes are indicative of central than peripheral vestibular syndrome. Apart from the minimum data base (complete blood count, serum biochemistry, urinalysis), the diagnostic evaluation should also include otoscopy, plain radiography of tympanic bullae (peripheral vestibular lesions), ear CT, brain MRI and cererebrospinal fluid analysis (central vestibular lesions). The present review first describes the clinical features of the vestibular syndrome from a differential point of view, regarding its neuroanatomical origin and secondly the most common conditions primarily characterized by vestibular dysfunction in the dog and cat.

Cochleovestibular gene transfer in neonatal mice by canalostomy.

Impairments of the inner ear result in sensorineural hearing loss and vestibular dysfunction in humans. A large proportion of these disorders are congenital, and involve both auditory and vestibular systems. Therefore, genetic interventions to correct deficits must be administered during early developmental stages. In this study, we evaluated inner ear gene transfer in neonatal mice by canalostomy using an adeno-associated virus serotype 8 (AAV8) vector. AAV8 with the green fluorescence protein (GFP) gene was inoculated into the inner ear of the neonatal mice through the posterior semicircular canal (canalostomy). At 30 days following surgery, animals were subjected to swim tests and auditory brainstem response measurements. Then, the animals were euthanized and temporal bones were harvested for whole-mount preparation. GFP expression and morphological changes in the inner ear were assessed by immunohistochemistry. After surgery, no signs of vestibular dysfunction were found, and there were no significant differences in the auditory brainstem response threshold between AAV8-inoculated ears and nonsurgery ears. In the surgery ears, extensive GFP expression and no morphological lesions were detected in the cochlear and vestibular end organs. Robust GFP expression was found in inner hair cells, marginal cells, vestibular hair cells, and vestibular supporting cells. In conclusion, AAV8 inoculation through canalostomy into the inner ears of neonatal mice led to extensive overexpression of exogenous genes in the inner ear without affecting hearing or vestibular function. It serves as a promising approach for gene therapy of congenital cochleovestibular diseases.

Subjective visual vertical after treatment of benign paroxysmal positional vertigo

IntroductionOtolith function can be studied by testing the subjective visual vertical, because the tilt of the vertical line beyond the normal range is a sign of vestibular dysfunction. Benign paroxysmal positional vertigo is a disorder of one or more labyrinthine semicircular canals caused by fractions of otoliths derived from the utricular macula. ObjectiveTo compare the subjective visual vertical with the bucket test before and immediately after the particle repositioning maneuver in patients with benign paroxysmal positional vertigo. MethodsWe evaluated 20 patients. The estimated position where a fluorescent line within a bucket reached the vertical position was measured before and immediately after the particle repositioning maneuver. Data were tabulated and statistically analyzed. ResultsBefore repositioning maneuver, 9 patients (45.0%) had absolute values of the subjective visual vertical above the reference standard and 2 (10.0%) after the maneuver; the mean of the absolute values of the vertical deviation was significantly lower after the intervention (p<0.001). ConclusionThere is a reduction of the deviations of the subjective visual vertical, evaluated by the bucket test, immediately after the particle repositioning maneuver in patients with benign paroxysmal positional vertigo.

Neurovestibular analysis and falls in Parkinson's disease and atypical parkinsonism.

The primary aim of our study was to determine the extent of vestibular dysfunction in patients with Parkinson's disease (PD). Our secondary aim was to determine if vestibular dysfunction in PD is a risk factor for falling. The tertiary aim was to determine both the extent of vestibular dysfunction and if this dysfunction is a risk factor for falling in patients with atypical parkinsonism (AP). Twenty-five healthy subjects, 30 PD patients and 14 AP patients were matched for age and gender in a case-control study design. All subjects underwent clinical neurological and neurotological assessments, cervical and ocular vestibular evoked myogenic potentials (VEMPs), brainstem auditory evoked potentials (BAEPs), subjective visual vertical measurements, and videonystagmography with caloric and rotatory chair stimulation. Ninety per cent of PD patients (27 of 30) and all 14 AP patients had signs of vestibular dysfunction on laboratory examinations. The evoked potential (VEMPs and BAEPs) test results of PD patients showed significant prolongation of the p13, n1 and interpeak III-V latencies on the symptomatic brainstem side (0.003≤ P≤0.019) compared with healthy subjects. Also, vestibular testing abnormalities were correlated with an increased risk for falling when fallers among PD and AP patients were compared with the non-fallers (P≤0.001). To conclude, vestibular dysfunction on vestibular laboratory testing is highly prevalent in both PD and AP patients compared with healthy subjects, and is associated with an increased risk for falling.

Time to Change from a Symptom-based Concussion Assessment to a Structured Physical Examination.

Time to Change from a Symptom-based Concussion Assessment to a Structured Physical Examination.

Clinical Features and Magnetic Resonance Imaging Findings in 7 Dogs with Central Nervous System Aspergillosis.

BackgroundSystemic aspergillosis is a manifestation of Aspergillus sp. infection that can result in central nervous system (CNS) involvement with marked alterations in CNS function. Information regarding the clinical presentation and magnetic resonance imaging (MRI) findings in cases of aspergillosis with CNS involvement is lacking, resulting in a need for better understanding of this disease.Hypothesis/ObjectivesThe primary objectives were to describe the clinical features and MRI findings in dogs with CNS aspergillosis. The secondary objectives were to describe clinicopathologic findings and case outcome.AnimalsSeven dogs with CNS aspergillosis.MethodsArchived records from 6 institutions were reviewed to identify cases with MRI of CNS aspergillosis confirmed with serum galactomannan enzyme immunoassay (EIA) testing, culture, or supported by histopathology. Signalment, clinical, MRI, clinicopathologic, histopathologic, and microbiologic findings were recorded and evaluated.ResultsAspergillosis of the CNS was identified in 7 dogs from 3 institutions. The median age was 3 years and six were German Shepherd dogs. Five dogs had signs of vestibular dysfunction as a component of multifocal neurological abnormalities. The MRI findings ranged from normal to abnormal, including hemorrhagic infarction and mass lesions.Conclusions and Clinical ImportanceUntil now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis.

Augmented asymmetrical visual field dependence in asymptomatic diabetics: Evidence of subclinical asymmetrical bilateral vestibular dysfunction

BackgroundDiabetes negatively affects the vestibular system in many ways, with vestibular dysfunction (VD), a co-morbidity with a high prevalence in diabetics. ProceduresThe ability to perceive subjective visual vertical (SVV), as a sign of vestibular dysfunction, and visual field dependence was measured using a computerized rod and frame test (CRAF). Alignment errors recorded from 47 asymptomatic Type II diabetics (no vertigo or falls, without peripheral neuropathy or retinopathy) were compared to 29 healthy age matched (46–69years) controls. FindingsVisual field dependence was significantly larger and more asymmetrical in the diabetics than controls. In the absence of any visual references, or when a vertical reference frame was provided, SVV perception was accurate in both groups, with no significant difference between the controls and diabetics. During tilted frame presentations, the proportion of subjects with either SVV deviations, or an asymmetry index, larger than an upper limit derived from the control data was significantly greater in diabetics than controls. ConclusionThese results suggest that the decreased ability to resolve visuo-vestibular conflict in asymptomatic diabetic patients (free of retinopathy and peripheral neuropathy) compared to controls may be related to diabetic complications affecting vestibular structures and thus causing a decompensation of subclinical vestibular asymmetries.

Aphysiologic performance on dynamic posturography in work-related patients

It has been suggested that malingering should be suspected in patients suffering from dizziness or imbalance and who had a potential gain associated with insurance and worker's compensation claims. This study aimed to assess and compare the prevalence of aphysiologic performance on computerized dynamic posturography (CDP) in patients with the potential for secondary gain using a retrospective review of two groups of patients: work-related patients referred for dizziness and/or imbalance (Group 1) were compared against a group of patients with complaints of dizziness or imbalance, who had no history of work-related injury, or litigation procedures (Group 2). CDP and videonystagmography (VNG) were carried out in all patients. The Sensory Organization Test summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in Otolaryngol Head Neck Surg 112:676-688 (1995). 24 out of 88 (27%) patients had aphysiologic CDP in Group 1 and 9 out of 51 (18%) in Group 2 but these differences were not significant (p > 0.05). Definite signs of vestibular dysfunction were found in 12 out of 24 (50%) of patients with aphysiologic performance in Group 1 although the presence of VNG abnormalities was significantly higher (p = 0.005) in Group 2. The hypothesis that the occupational group could show a significantly higher rate of aphysiologic results than a control group is not confirmed. Furthermore, VNG abnormalities were found in 50% of the work-related cases with non organic sway patterns. These results suggest that patient's complaints should be considered genuine in work-related cases and due caution exercised when evaluating aphysiologic CDP patterns.

Pusher syndrome in patients with cerebellar infarctions?

Acute supratentorial unilateral stroke can lead to an impairment of head and body posture and balance that manifests as an active pushing away from the non-paralyzed side in order to maintain an upright posture, i.e., socalled pusher syndrome (PS). Besides supratentorial lesions [1–3], there have also been claims of PS occurring in patients with cerebellar lesions [4]. Thus, we aimed to answer the question whether the PS can be found regularly in patients with cerebellar lesions. A total of 19 patients with acute cerebellar stroke, documented by magnetic resonance imaging (MRI) (time since lesion, mean ± standard deviation (SD): 4.0 ± 2.2 days) were classified based on the criteria of the Scale for Contraversive Pushing [1]. All patients underwent neurootological examinations including otolith testing by means of the subjective visual vertical (SVV) [5, 6]. None of the patients showed PS (mean score 0). However, if the criterion of a ‘‘pathological tilt’’ of SVV of [2.5 on our data is applied [5], 9 patients (48%) presented with contralesional tilt (9.1 ± 7.1 ) and 5 (26%) with ipsilesional tilt of SVV (5.1 ± 2.9 ). Five patients (26%) had no pathological tilt. Thus, our data indicate that PS is not a common sign in patients with acute cerebellar lesions, whereas an otolith deficit with tilts of SVV regularly occurred [6]. Therefore, contrary to a cortical level where an association between PS and SVV tilt was reported [3, 7] and points toward otolith dysfunction in PS patients, at a cerebellar level such an association could not be verified by our data. Indeed, one might even speculate that PS does not exist in cerebellar stroke patients. The case report describing a patient with gait ataxia that presented 1 week later with a ‘‘strong pusher behavior when standing’’ whereas ‘‘independent sitting was possible, but not standing without help’’ [4] has to be discussed with caution. The authors attributed these signs to a PS toward the affected side caused by a large cerebellar infarction [4]. The lesion site of the infarction could only be documented by CT scan. However, CT scan’s resolution is not adequate to detect small brainstem lesions at the medullary level which often accompany cerebellar infarctions. Indeed, an additional small affection of the medulla might be an important aspect since lateral medullary lesions can cause severe body lateropulsion, i.e., a strong irresistible tendency to fall to one side even with the eyes open [8–10]. This ipsilateral axial lateropulsion might appear similar to PS and, thus, can be mixed up, especially when it occurs in the standing and not in the sitting body position as was the case in patient described by Paci and Nannetti [4]. Body lateropulsion in medullary infarcts may occur without signs of vestibular dysfunction (e.g., tilts of SVV) and without limb ataxia: it reflects an impairment of vestibulospinal postural control caused by a lesion of the descending lateral vestibulospinal tract as described with three-dimensional brainstem mapping based on MRI [10]. Body lateropulsion with limb ataxia is probably the consequence of impaired or absent proprioceptive information caused by a lesion of the ascending dorsal spino-cerebellar tract [10]. The observation of the present data that patients with cerebellar lesions show contraor ipsilesional tilt of SVV B. Baier (&) M. Dieterich Department of Neurology, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany e-mail: baierb@uni-mainz.de

How to…

The clinical signs of vestibular dysfunction relate to abnormalities in gait, posture and ocular movements. Ane Uriarte and Rodolfo Cappello describe how to interpret the clinical signs, identify the causes of the condition, and treat the patient.

Active versus passive head-shaking nystagmus

Conclusions. We recommend performing the test for nystagmus actively, both when the response is analyzed at bedside or with videonystagmography. If no nystagmus is observed with the active test, it should then be performed passively. Objective. Head-shaking nystagmus (HSN) is a sign of vestibular dysfunction that is elicited after actively (patient) or passively (examiner) shaking a patient's head. The objective of this study was to analyze the frequency of HSN when the test is performed actively (aHSN) or passively (pHSN), and to determine whether any differences in the results might be due to age or disease state, or whether they reflect the results of different vestibular tests. Patients and methods. This was a prospective study conducted at a tertiary care center. The head-shaking test was carried out actively and passively on 100 patients. The caloric test, the rotatory chair tests and the measures of disability were performed on the same day and in the same setting. HSN was considered to be present when it was seen for a period longer than 5 s or if the maximum slow-phase velocity of HSN was higher than 3°s−1. Four groups were established according to the results of the two testing methods. Results. The frequency of aHSN was 47% and of pHSN was 46% when the presence of nystagmus was established as the criterion. Moreover, in patients who had experienced vestibular neuritis previously, the type of nystagmus was age-dependent. When the velocity of the nystagmus elicited was considered, the results coincided with the method of testing in 74% of the patients, while they differed in 26% of subjects; the aforementioned age dependency was no longer seen. Differences in the caloric and rotatory chair test results, as well as in disability, were observed in the groups generated on the basis of the types of nystagmus.

An Animal Model of Sudden Onset Sensorineural Hearing Loss with Vestibular Function Disturbances Induced By Mitochondrial Toxin

Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol/L (3-NP (H)) and 0.3 mol/L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses(ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. Animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP(H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3-NP (H) exposure. The rate of complete ABR loss decreased as post-treatment test time increased. ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H)-treated animals and in 20 % (1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP(H) and 40% (2/5) of animals exposed to 3-NP(L), except for the one animal treated bilaterally, which showed no signs of imbalance. Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at 12 hours post-3-NP (H) exposure, progressed at day 3 and recovered at day 7. Vacuoles in the cellular plasm and nucleus was seen as early as at 12 hours post-3-NP exposure in the spiral ganglion cells, and signs of degeneration were visible at day 7. Conclusion Inner ear exposure to 3-NP through the round window membrane appears to reproduce clinic manifestations and may serve as a legitimate animal model of SSNHL

A topodiagnostic investigation on body lateropulsion in medullary infarcts

Body lateropulsion may occur without signs of vestibular dysfunction and vestibular nucleus involvement. The authors examined 10 such patients with three-dimensional brainstem mapping. Body lateropulsion without limb ataxia reflected an impairment of vestibulospinal postural control caused by a lesion of the descending lateral vestibulospinal tract, whereas body lateropulsion with limb ataxia was probably the consequence of impaired or absent proprioceptive information caused by a lesion of the ascending dorsal spino-cerebellar tract.

Characterization of the Effects of N-Hydroxy-IDPN on the Auditory, Vestibular, and Olfactory Systems in Rats

The mechanism of neurotoxicity of 3,3′-iminodipropionitrile (IDPN) has been widely debated, with either the parent compound or putative metabolites implicated in various studies. The N-hydroxylated form of IDPN (HO-IDPN) has been reported to cause the excitation with choreiform and circling (ECC) syndrome in rats at doses approximately one-eighth of that required to cause comparable signs in rats treated with IDPN. Because of the similarity of symptoms induced by HO-IDPN and IDPN, we investigated the effect of HO-IDPN on other aspects of the nervous system affected by IDPN, specifically the auditory, vestibular, and olfactory systems. In addition, ECC symptoms were quantified to replicate the previous findings. HO-IDPN was administered ip in saline for 3 consecutive days to two different cohorts of young adult male Sprague-Dawley rats. The first cohort (60, 80, 100, and 120 mg/kg; n = 2/group, except for the 120 mg/kg group, where n = 1) was used in a dose range-finding study. After making the neurobehavioral assessments, animals were sacrificed for olfactory mucosal histopathology. Based on the outcome of the first study, the second cohort (n = 10/group) received saline or HO-IDPN at 100 mg/kg/day for 3 consecutive days. Two animals from each of these groups were sacrificed for olfactory mucosal histopathology; the remaining animals were tested for neurobehavioral effects 3 weeks after the last dose. Animals in the second cohort lost approximately 8% of their pretreatment body weight. All rats receiving the 100 mg/kg/day dose of HO-IDPN (and the rat receiving 120 mg/kg/ day) developed the ECC syndrome and signs of vestibular dysfunction within 4 days after the last dose. HO-IDPN caused a large decrease in the acoustic startle response and markedly elevated auditory thresholds at all frequencies tested. The threshold for the ECC syndrome and olfactory mucosal damage was 100 mg/kg. These studies extend previous findings on the neurotoxicity of HO-IDPN and point to the need for determining whether HO-IDPN is an in vivo metabolite of IDPN.