Frequency Of Spontaneous Nystagmus Research Articles

The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats

Background Diazepam, a gamma-aminobutyric acid type A receptor agonist, is classified as a vestibular suppressant and is effective in treating acute vertigo. However, its effects on vestibular compensation (VC) remain unclear. Objectives We examined the effects of continuous administration of diazepam on the frequency of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) as an index of the initial process of VC in rats. Materials and methods Diazepam was continuously administered at doses of 3.5 and 7.0 mg/kg/day, intraperitoneally, via an osmotic minipump. The frequency of SN beating against the lesion side after UL was measured. Potassium chloride (KCl) solution (1 M) was injected intratympanically to induce SN beating to the injection side. Results Continuous administration of diazepam significantly and dose-dependently decreased the frequency of SN after UL, and also reduced the x intercept of the nonlinear regression curve of the decline in UL-induced SN with time in rats. However, the continuous administration of diazepam did not affect the frequency of intratympanic KCl-induced SN in the rats. Conclusion These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.

Effects of Betahistine on the Development of Vestibular Compensation after Unilateral Labyrinthectomy in Rats.

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.

Rapid vestibular compensation in guinea pig even with prolonged anesthesia

The results of previous studies have suggested that prolonged anesthesia following unilateral labyrinthectomy (UL) results in a retardation of vestibular compensation, the process of behavioral recovery that occurs following the lesion. In this study we investigated the effects of short-term (25 min) and long-term (4 h) anesthesia with isoflurane on the time course of vestibular compensation following UL in guinea pig. Although there were significant differences in the frequency of spontaneous nystagmus (SN) ( p < 0.05) and its rate of compensation ( p < 0.05) between the 25 min and 4 h isoflurane groups, these differences appeared to be due largely to the 5, 9 and 13 h time points. There was also a significant difference in the rate of yaw head tilt (YHT) compensation, largely due to the 5 h time point. When exponential regression analysis was performed to evaluate the overall pattern of compensation, there was no significant difference in the time required to reach 100% SN or YHT compensation between the 25 min and 4 h isoflurane groups. Furthermore, there were no significant differences in roll head tilt (RHT) compensation between the two groups. These results suggest that the time course of vestibular compensation is largely independent of the duration of the anesthesia used for UL surgery.

The effects of intra-vestibular nucleus administration of brain-derived neurotrophic factor (BDNF) on recovery from peripheral vestibular damage in guinea pig.

Brain-derived neurotrophic factor (BDNF), at doses of 0.04, 0.4 or 4.0 microg/day, was delivered by cannula and s.c osmotic minipump into the ipsilateral vestibular nucleus complex from 0 to 50 h following unilateral labyrinthectomy (UL) in guinea pigs. Compared to the vehicle control group, the frequency of spontaneous nystagmus was significantly reduced (p < 0.02) and the rate of yaw head tilt compensation increased (p < 0.02). However, roll head tilt was not signifcantly affected. There were also no significant effects of BDNF administration into the IVth ventricle (4.0 microg/day) on any UL symptom. These results further support the hypothesis that neurotrophins such as BDNF may enhance the vestibular compensation process.

Effectiveness and Utility of Chemical Labyrinthectomy with Streptomycin Using Osmotic Pump

To investigate the utility of osmotic pumps, labyrinthectomy was performed surgically (surgical group) or chemically with 30% streptomycin sulfate (SM) using osmotic pumps (SM group) in guinea pigs. After treatment, no statistical difference was observed in the frequency of spontaneous nystagmus and the degree of yaw head tilt between the groups. These data indicate the reliability and efficacy of osmotic pumps, and it might be possible to make guinea pig models using osmotic pumps to predict various grades of damage in the vestibular periphery of humans.

Effects of Nitric Oxide on the Vestibular Functional Recovery After Unilateral Labyrinthectomy

The effects of nitric oxide on the vestibular function recovery following unilateral labyrinthectomy were studied. Male Sprague-Dawley rats treated with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, were subjected to destruction of the unilateral vestibular apparatus and spontaneous nystagmus was observed. To explore the role of nitric oxide on the potassium current, the whole cell patch clamp technique was applied on isolated medial vestibular nuclear neurons. The frequency of spontaneous nystagmus that appeared in L-NAME-treated rats was higher and maintained longer than in control animals. Potassium currents in the isolated medial vestibular nucleus were inhibited by nitric oxide liberating agents, sodium nitroprusside and S-nitroso-N-acetylpenicillamine. After blockade of calcium dependent potassium currents by high EGTA (11 mM)-containing pipette solution, sodium nitroprusside did not inhibit the outward potassium currents. 8-Bromoguanosine 3,5-cyclic monophosphate, a membrane-permeable cGMP analogue, produced similar effects to inhibit the outward potassium currents as sodium nitroprusside. These results suggest that nitric oxide production after unilateral labyrinthectomy would help to facilitate vestibular compensation by inhibiting calcium-dependent potassium currents through increasing intracellular cyclic GMP, thereby increasing excitability in ipsilateral vestibular nuclear neurons.

高齢モルモットの前庭代償機能

To determine age-related changes in vestibular compensation we measured the frequency of spontaneous nystagmus and yaw head tilt after unilateral labyrinthectomy. Albino guinea pigs were divided into two groups: the control group (3 to 12 months of age; n=8) and the aged group (36 to 39 months of age; n=3). We found that the frequency of spontaneous nystagmus in the aged group was significantly lower than in the control group (p<.05). The time constant for spontaneous nystagmus in the aged group was shorter than that in the control group. No significant difference was found in yaw head tilt between the two groups. We conclude that the function of vestibular compensation is not affected by aging. We suggest that the decline of spontaneous nystagmus in the aged group may be due to the diminution of resting activity in two vestibular nuclei.

Methylprednisolone reduces spontaneous nystagmus following unilateral labyrinthectomy in guinea pig

The present study investigated the effects of methylprednisolone on the vestibular compensation process following unilateral labyrinthectomy in guinea pigs. A single injection of methylprednisolone (15, 30 or 60 mg/kg s.c.), 15 min pre-labyrinthectomy, had no significant effect on either the severity or the rate of compensation of spontaneous ocular nystagmus or yaw head tilt; roll head tilt showed a significant change in the rate of compensation ( P < 0.005), due to increased roll head tilt in the 60 mg/kg group. However, a pre-labyrinthectomy injection of 30 mg/kg s.c. methylprednisolone followed by a second 30 mg/kg injection at 4 h post-labyrinthectomy resulted in a significant reduction in spontaneous nystagmus frequency ( P < 0.005) and a significant change in the rate of spontaneous nystagmus compensation ( P < 0.005). The additional 30 mg/kg injection had no significant effect on the magnitude or compensation of the postural symptoms. These results indicate that, at the optimal dose of 30 mg/kg, 2 injections of methylprednisolone (15 min pre-labyrinthectomy and 4 h post-labyrinthectomy) result in a significant reduction in spontaneous nystagmus frequency.

Effect of sensory deprivation or electrical stimulation on acute vestibular symptoms following unilateral labyrinthectomy in rabbit.

The effect of sensory deprivation or electrical stimulation on vestibular compensation was investigated for 7 days after unilateral labyrinthectomy (ULX) in 50 rabbits. Eye movements induced by sinusoidal rotation of the whole body and spontaneous nystagmus were measured for vestibulo-ocular compensation, and head deviation was measured for vestibulospinal compensation. The rabbits were divided into 4 groups: one with ULX only (LX only), ULX with bilateral tarsorrhaphy (LX+TX), ULX with cervical dorsal root ganglionectomy (LX+GX), and a group stimulated electrically on the lesion-sided vestibular system with square pulse for 8 h/day (LX+ES). In LX only, the frequency of spontaneous nystagmus was 2.93 +/- 0.19 beats/sec just after ULX, declining to zero in 4 days. In eye movements induced by sinusoidal rotation on the 7th day after ULX, directional preponderance was 24-43% and gain decreased to 32-48% by rotation toward the intact side and 17-29% by rotation toward the lesion side, compared with that before ULX. Roll head tilt and yaw head tilt were 82 +/- 9 degrees, 45 +/- 6 degrees, respectively, on the 7th day. Recovery of vestibulo-ocular reflex and head deviation was delayed in LX+TX and LX+GX compared with that in ULX only, but recovery was enhanced in LX+ES. Therefore, in this study, electrical stimulation of the lesion side seemed to have a favorable effect on suppression of acute vestibular symptoms induced by unilateral vestibular lesion.

A dose‐response analysis of the beneficial effects of the ACTH‐(4–9) analogue, Org 2766, on behavioural recovery following unilateral labyrinthectomy in guinea‐pig

1. After removal of the peripheral vestibular receptors in one inner ear (unilateral labyrinthectomy, UL), oculo-motor and postural symptoms occur but disappear over time in a process of recovery known as vestibular compensation. 2. ACTH-(4-10), a fragment of the adrenocorticotrophic hormone (ACTH) molecule, which is devoid of corticotrophic activity, has been shown to enhance vestibular compensation. The present study investigated the effect of the ACTH-(4-9) analogue, Org 2766, on vestibular compensation in guinea-pig. Org 2766 is reported to be more potent behaviourally than ACTH-(4-10). 3. After UL, Org 2766 was delivered via an osmotic minipump implanted s.c. to 30 animals randomly assigned to one of five conditions: 1, 5, 10, 20 or 40 nmol kg-1 Org 2766, every 4 h for 52 h post-UL. Although infusion was continuous, in the present study the doses are expressed as nmol per 4 h in order to compare the results to a previous study in which animals received a discrete dose of ACTH-(4-10) at the end of each 4 h period. All animals were compared to saline controls (n = 6). 4. Three symptoms of UL, spontaneous ocular nystagmus, roll head tilt and yaw head tilt, were measured every 4 h for 52 h, beginning at 10 h post-UL. 5. Rates of infusion of 1, 5 and 10 nmol kg-1 accelerated spontaneous nystagmus compensation; 20 nmol kg-1 produced a significant decrease in the frequency of spontaneous nystagmus, as well as accelerating its compensation; 40 nmol kg-1 had no significant effect on spontaneous nystagmus compensation. 6. In comparison to the effects of Org 2766 on spontaneous nystagmus compensation, Org 2766 had little effect on the compensation of the postural symptoms, yaw head tilt and roll head tilt. Only 5 and 40 nmol kg-1 produced a significant change in postural compensation, and this was a reduction in the rate of roll head tilt compensation.7. At the optimal infusion rate of 20 nmol kg-1 every 4 h, Org 2766 produced a similar effect on spontaneous nystagmus compensation to that of ACTH-(4-10). However, Org 2766 was effective in accelerating spontaneous nystagmus compensation at much smaller doses per 4 h period than ACTH-(4-10). Org 2766 did not have the same effect on. postural compensation as it had on the compensation of spontaneous nystagmus.

Comparison of the effects of pretreatment with competitive or noncompetitive NMDA antagonists on vestibular compensation

Unilateral labyrinthectomy (UL) results in a syndrome of ocular motor and postural disorders which abates over time in a process of behavioural recovery known as vestibular compensation. We have previously reported that a single systemic pre-UL injection of the organic Ca 2+ channel antagonist verapamil or the noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonist MK-801 reduces the behavioural effects of UL in guinea pigs. The present study was conducted to determine if similar effects would be obtained with single injections of the competitive NMDA receptor antagonists 3-[(±)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) or cis-4-(phosphonomethyl)-piperidine-2-carboxylic acid (CGS 19755). Guinea pigs received an IP injection of 5 mg/kg CPP 2.5 h pre-UL, 5 or 10 mg/kg CPP 1 h pre-UL, 10 or 20 mg/kg CGS 19755 1 h pre-UL, or 1 ml/kg vehicle (saline) 1 h pre-UL, and the effects on the compensation of spontaneous nystagmus were measured over the following 52 h post-UL. Pretreatment with CPP had no significant effect on spontaneous nystagmus frequency or its compensation over 52 h post-UL. However, pretreatment with CGS 19755 resulted in a significant decrease in spontaneous nystagmus frequency without any acceleration of the rate of compensation.

Injections of calmidazolium chloride into the ipsilateral medial vestibular nucleus or fourth ventricle reduce spontaneous ocular nystagmus following unilateral labyrinthectomy in guinea pigs.

The effects of three injections (0.5-4.5 h post-operation) of 1-[bis-(p-chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4- dichlorobenzyloxy)phenethyl]-imidazolium chloride (calmidazolium chloride, R24571), into the ipsilateral medial vestibular nucleus or fourth ventricle, on vestibular compensation for unilateral labyrinthectomy was studied in guinea pigs. R24571, a calmodulin antagonist and inhibitor of several Ca(2+)-dependent enzymes, caused a significant reduction in the average frequency of spontaneous ocular nystagmus (spontaneous nystagmus) during the first 53 h following unilateral labyrinthectomy (n = 5), compared with vehicle-injected animals (n = 5). Although a statistical analysis was not performed on the yaw head tilt and roll head tilt data because of the large variability between animals over the 53-h period of compensation, most R24571-treated animals had less yaw head tilt (4/4 animals) and roll head tilt (4/5 animals) at 9-11 h post-labyrinthectomy than the average values for the vehicle groups at that time. The decrease in the frequency of spontaneous nystagmus following R24571 treatment was not associated with general ataxia or sedation. These results are consistent with recent biochemical studies in suggesting that intracellular pathways associated with Ca2+ may be involved in the neuronal mechanisms of vestibular compensation following unilateral labyrinthectomy.

Evaluation of Effects of Treatment Based on Natural Course of Meniere's Disease

Some patients with Meniere's disease undergo natural remission of their vertigo, although it is almost always difficult to establish the natural course of Me-niere's disease because of its episodic fluctuating course. In the present study, the natural course of Meniere's disease in the acute stage was examined in six patients. Their subjective and objective symptoms (frequency of spontaneous nystagmus, caloric test and pendular rotation test) were compared with the course of remission in 6 patients treated with steroids. All patients were followed every week for 8 weeks or more. The subjective effect was expressed as the spell index calculated by multiplying duration by number of vertigo attacks in a week in order to amalgamate both intensity and frequency into a single score. Significant decreases (p<0.05) in the spell index and the number of nystagmus were demonstrated during the first two weeks, and then a gradual decrease was noted. Although no difference in caloric excitability was noted between the start and the end of the trial, rotation directional preponderance was significantly (p<0.05) reduced. Subjective improvement of the spell index was significantly (p<0.001) associated with the improvement in the objective results of nystagmic beats. The bound effect of the drug based on natural remission was markedly demonstrated during the first period. Evaluation of the effect of treatment of vertigo should be performed on the basis of natural remission. Further examination is necessary to establish the natural course of Meniere's disease.

Pretreatment with MK-801 reduces spontaneous nystagmus following unilateral labyrinthectomy

Unilateral labyrinthectomy results in a syndrome of ocular motor and postural symptoms which abate over time in a process of behavioural recovery known as vestibular compensation. We have previously suggested that an increased Ca 2+ influx in ipsilateral vestibular nucleus (VN) neurons at the time of the unilateral labyrinthectomy may exacerbate the depresssion of VN resting activity caused by the loss of excitatory input from the VIIIth nerve. In order to further test this hypothesis, we administered ( + )-5-methyl-10,11-dihydro-5H-dibcnzo[a,d]cyclohcptcn-5,10-imine hydrogen maleate (MK-801; 1.0 or 2.5 mg/kg i.p.), which blocks Ca 2+ influx via NMDA receptor-mediated ion channels, to guinea pigs 0.5 h before unilateral labyrinthectomy and examined the effects on three symptoms of unilateral labyrinthectomy: spontaneous ocular nystagmus, yaw head tilt and roll head tilt. Pretreatment with MK-801 significantly altered the time course of the vestibular compensation of spontaneous nystagmus and yaw head tilt but had no significant effect on roll head tilt; in particular, 2.5 mg/kg MK-801 depressed spontaneous nystagmus frequency at 10 and 20 h post-labyrinthectomy relative to saline controls ( P < 0.05, post-hoc Scheffé F-test). The reduction in spontaneous nystagmus frequency was not simply a result of extended anesthesia, since other control animals, which received additional injections of the general anesthetic in order to achieve equivalent sleep times to the MK-801 group, did not show reduced spontaneous nystagmus frequency. These results provide preliminary evidence that Ca 2+ influx through NMDA receptor-mediated channels at the time of the unilateral labyrinthectomy may be important to the generation of the ocular motor and postural symptoms which follow, and that recovery from the effects of this Ca 2+ influx may be important to the initiation of vestibular compensation.

A study on preoperative electronystagmography in chronic otitis media

Preoperative electronystagmography (ENG) recordings were done in 100 patients with chronic otitis media to detect vestibulocular disturbance associated with this condition.ENG recordings were performed under five conditions : gazing, eyes closed, eyes covered and performance of mental calculation with eyes closed and eyes covered. The optokinetic pattern test (OKP) and eye tracking test (ETT) were also done.The rate of appearance of spontaneous nystagmus in these 100 patients was compared with the rate of appearance of the 100 normal individuals in the report of Kaga et al. Both slow phase velocity (degree/second) and frequency (number/second) were measured on ENG recordings and also compared with the normal results. The relation between the rate of appearance of the spontaneous nystagmus with the following clinical signs and symptoms were investigated : 1) vertigo, 2) otorrhea, 3) unilateral, or bilateral chronic otitis media, 4) history of operation, 5) cholesteatoma and 6) bone conduction abnormalities. Spontaneous nystagmus was found in 67% of the patients with chronic otitis media. Both slow phase velocity and frequency of spontaneous nystagmus of the patients were remarkably larger than that of the normal individuals in each of the above conditions. Significant difference was seen with respect to the following : vertigo, bone conduction abnormalities and unilateral cholesteatoma. The direction of the spontaneous nystagmus in patients with unilateral chronic otitis media with otorrhea was contralateral to the lesion rather than ipsilateral. Six patients showed abnormal optokinetic patterns and they also had abnormal results on the eye tracking test.