Timo P. Hirvonen

Subclinical vestibulocerebellar dysfunction in migraine with and without aura

Objective: In patients with migraine, neurotologic symptoms and signs occur commonly. The authors’ aim was to determine whether neurotologic findings are in accordance with the type of migraine and whether test findings differ from those of healthy controls. Methods: The authors examined 36 patients with various types of migraine classified by International Headache Society criteria. Comprehensive neurotologic tests were performed between attacks: video-oculography (VOG), electronystagmography, static posturography, and audiometry on 12 patients with migraine with aura (MA) and 24 patients with migraine without aura (MO). Results were compared to those of test-specific nonmigrainous control groups. Only eight migraineurs (six with MA and two with MO) had vertigo or dizziness. Results: Despite the absence of clinical neurotologic symptoms, most of the patients with migraine (83%) showed abnormalities in at least one of these tests. Both migraine types differed significantly from the control group (in VOG, in saccadic accuracy, and in static posturography). Vestibular findings tended to be more severe in MA than in MO. Conclusions: These data suggest that interictal neurotologic dysfunction in MA and MO share similar features and that the defective oculomotor function is mostly of vestibulocerebellar origin.

Acoustic responses of vestibular afferents in a model of superior canal dehiscence.

Hypothesis: Afferents innervating the superior semicircular canal are rendered especially sensitive to acoustic stimulation when there is a dehiscence of the superior canal. Other vestibular end organs are also more sensitive to acoustic stimulation. Background: Dehiscence of the superior semicircular canal is associated with vertigo and nystagmus caused by loud sounds (Tullio phenomenon) or changes in middle ear or intracranial pressures. The mechanisms by which acoustic stimuli act on the vestibular end organs are unclear. The nystagmus caused by acoustic stimuli generally aligns with the affected superior canal. Methods: Responses to acoustic stimuli in the superior vestibular nerves of anesthetized chinchillas were recorded before and after fenestration of the superior canal. Results: Two acoustic response patterns were seen: rapid phase locking and slow tonic changes in firing rate. Phasic responses principally occurred in irregular afferents and tonic responses in regular afferents. Afferents from all of the vestibular end organs encountered could respond to acoustic stimuli, even before fenestration. However, fenestration lowered the thresholds for acoustic stimulation in superior canal afferents with phasic responses and increased the magnitude of tonic responses. Conclusions: Superior canal dehiscence may render the irregular afferents innervating the superior canal particularly sensitive to loud sounds. Rapid phase-locking responses may explain the short latency of nystagmus seen in patients with superior canal dehiscence syndrome. The mechanisms by which acoustic stimuli activate the vestibular end organs may differ from the damped endolymph motion associated with head acceleration.

Disruption of the Head Direction Cell Signal after Occlusion of the Semicircular Canals in the Freely Moving Chinchilla

Head direction (HD) cells in the rat anterodorsal thalamic nucleus (ADN) fire relative to the animals directional heading. Lesions of the entire vestibular labyrinth have been shown to severely alter VIIIth nerve input and disrupt these HD signals. To assess the specific contributions of the semicircular canals without altering tonic VIIIth nerve input, ADN cells were recorded from chinchillas after bilateral semicircular canal occlusion. Although ADN HD cells (and also hippocampal place cells and theta cells) were identified in intact chinchillas, no direction-specific activity was seen after canal occlusions. Instead, “bursty” cells were observed that exhibited burst-firing patterns similar to normal HD cells but with firing unrelated to the animals actual head direction. Importantly, when pairs of bursty cells were recorded, the temporal order of their firing was dependent on the animals turning direction, as is the case for pairs of normal HD cells. These results suggest that bursty cells are actually disrupted HD cells. The present findings further suggest that the HD cell network is still able to generate spiking activity after canal occlusions, but the semicircular canal input is critical for updating the network activity in register with changes in the animals HD.

Intratympanic and Systemic Dexamethasone for Ménière’s Disease

Intratympanic and systemic dexamethasone treatment of Ménière’s disease (MD) was evaluated in a prospective study. Seventeen patients (6 men and 11 women) with MD (5 right-sided, 11 left-sided and 1 bilateral) were treated with three 0.2- to 0.4-ml injections of intratympanic dexamethasone hyaluronate (16 mg/ml) during a week and with an initial intramuscular dexamethasone injection of 15 mg. Most of patients were in stage 3, and the mean duration of MD was 5.3 years. Pure-tone and speech audiometry and the symptom scale of the patients were followed up for 1 year after the treatment. Symptoms of aural fullness, hearing loss, tinnitus and vertigo did not improve significantly. However, sufficient control of vertigo was achieved in 76% of the patients. In conclusion, no definite treatment effect has yet been shown for intratympanic and systemic dexamethasone treatment. Therefore, the clinical use of dexamethasone in MD needs further investigation.

Changes in Vestibulo-ocular Reflex of Elderly People

Dizziness is a common symptom in elderly people. Head autorotation test (HART) has earlier shown no significant vestibulo-ocular reflex (VOR) disturbances in healthy elderly subjects. We used our recently developed HART to determine VOR in 14 elderly volunteers without otoneurological diseases and sedative medications. Gain and phase were determined in 5 frequency bands from 0.5 to 5 Hz. The gain of the elderly was significantly increased to 1.11-1.27 in the frequency range of 3-5 Hz compared with the controls. The phase lead of 7-8 degrees in the frequency bands of 2 and 4 Hz differed significantly from normative values of the controls. The percentage of the elderly to reach high-frequency head movements was diminished to 50% in the frequency band of 3 Hz and to 36% in the frequency band of 4 Hz (controls 100% and 95%, respectively). The individual HART results were abnormal in 86% of the elderly. The high-frequency VOR of the elderly was inaccurate in magnitude and timing. More than half of aged subjects were not able to generate voluntary fast head movements. These findings may explain the high prevalence of dizziness and falls in elderly subjects.

Nystagmus Measured with Video-Oculography: Methodological Aspects and Normative Data

Detailed analysis of eye movements is essential in order to understand the pathophysiology underlying vestibular disturbances. We applied a commercial video-oculography (VOG) to measure spontaneous and provoked nystagmus in 20 healthy subjects. The slow-phase velocity (SPV) of the nystagmus was calculated. We also simultaneously recorded the eye movements on a standard VHS videotape to be able to confirm the results derived from the VOG paper charts. The nystagmus results derived from the VOG charts and the simultaneous videotaping agreed well. Nystagmus was found in 17 subjects. Spontaneous nystagmus was seen in 20%, positional nystagmus in 55%, and head-shaking nystagmus in 35% of the participants. Although nystagmus was frequent (85%), the mean SPV for nystagmus was low (1.7°/s). The VOG is a modern and sensitive method to record eye movements, but visual inspection of the videotape may be needed in selected cases to confirm occurrence of nystagmus.

Acetazolamide improves neurotological abnormalities in a family with episodic ataxia type 2 (EA-2).

Sirs: Episodic ataxia type 2 (EA-2) is a rare neurological disease characterized by episodes of vertigo, ataxia, nystagmus, nausea, vomiting, fatigue, and often migraine. EA-2 is inherited as an autosomal dominant trait of the CACNA1A gene mutations on chromosome 19p13. CACNA1A encodes the alpha1A-subunit of a voltage dependent P/Q-type calcium channel that is mainly expressed in the Purkinje cells of the cerebellum [8, 11]. Neurological examination of EA-2 patients can vary from normal to severe cerebellar ataxia. On oculomotor studies interictal gazeevoked, rebound, and downbeat nystagmus have been common findings together with saccade hypermetria. These findings localize to the oculomotor region of the posterior vermis and the fastigial nuclei [3, 4, 9]. Acetazolamide is effective in suppressing attacks in EA-2 [2, 4, 7], but has not been shown to improve oculomotor signs in EA-2 [2, 5]. We, therefore, wanted to evaluate the effect of acetazolamide on oculomotor and postural function in an EA-2 family (Fig. 1) with a novel CACNA1A splice site mutation IVS36–2A > G (Kaunisto et al., Neurogenetics, in press). There were 13 affected individuals in the family of whom four were on acetazolamide. The clinical picture of the family has been described in detail earlier (Kaunisto et al., Neurogenetics, in press). The video-oculography (VOG) including recording of spontaneous and provoked nystagmus, ENG (with caloric and saccadic tests), static posturography, and pure tone audiometry were carried out to three EA-2 patients (III-13, III-16, III-22 in Fig. 1) with and without acetazolamide (one week washout time, patient III-22 three days). Their neurological examination and brain MRI were normal.

Vestibulo-ocular reflex function as measured with the head autorotation test.

The vestibulo-ocular reflex (VOR) of 125 healthy subjects was examined over the frequency range of 0.5-5 Hz with the head autorotation test (HART). During the HART the subjects fixated at a steady target while moving their heads horizontally from side to side with increasing frequencies according to auditory signals. The gain was determined as the ratio between the amplitude of the eye and head movements in five frequency bands between 0.5 and 5 Hz. The phase difference between the eye and head movements was determined in both degrees and milliseconds. The ability to reach high-frequency bands was evaluated. The mean gain was close to unity up 5 Hz, when it decreased to 0.91. The mean phase difference showed a lead of approximately 5 degrees at frequencies below 2 Hz, and at frequencies above 2 Hz there was no phase difference within the resolution of the test. The frequency band of 5 Hz was reached by 78% of the subjects, and that of 4 Hz was reached by 94% of the subjects. In summary, the HART is a new approach with which to study VOR function and determine accurately the VOR for healthy subjects. The normal upper frequency limit is 4 Hz in the HART.

Cochlear implantation rarely alters horizontal vestibulo-ocular reflex in motorized head impulse test.

Objective Determine the change in vestibular function in patients receiving a unilateral cochlear implant, and to compare these results with other signs and symptoms. Study Design Prospective cohort study. Setting Academic tertiary referral center. Patients Forty-four adults (mean age, 55 yr; range, 30–76 yr) receiving their first cochlear implant. Intervention Cochlear implantation. Main Outcome Measures Horizontal high-frequency vestibulo-ocular reflex (VOR) was measured using the motorized head impulse rotator preoperatively and twice (on average two and 19 months) postoperatively. VOR gain and asymmetry were calculated (mean ± standard deviation). Symptoms were assessed with a structured questionnaire. Results Gain on the operated side was 0.77 ± 0.26 preoperatively, 0.75 ± 0.30 in the early and 0.73 ± 0.33 in the late postoperative control, and did not change significantly. Mean asymmetry remained within 9% to 10% in all test occasions. Dizziness symptom score or dizziness-related quality of life score did not change significantly. General quality-of-life score improved significantly from that of preoperative 3.5 ± 1.2 to that of 2.6 ± 1.1 postoperatively (p = 0.01). Subjective hearing scores improved significantly from 4.9 ± 0.3 to 2.4 ± 1.0, respectively (p = 0.0000). Gain was decreased significantly in 4 patients (10%) in the early and in 2 patients (7%) in the late postoperative control. Conclusion Late high-frequency loss of vestibular function or vestibular symptoms is rare but possible after cochlear implantation surgery. This should be taken into account in patient counseling especially when considering bilateral cochlear implant surgery.

Postural Control Measured by Visual Feedback Posturography

The objective was to study the applicability and repeatability of visual feedback posturography (VFP) in assessing postural control of 23 healthy subjects. The subjects had to move their center of gravity (COG) marker on a computer screen to chosen targets by leaning their body on the platform, and the accuracy, velocity, and side difference of these movements were measured. The intraclass correlation coefficients for all parameters during repeated tests were significant (r = 0.93–0.96; p < 0.01). Hold percentage within the targets and COG marker velocity to the targets did not change significantly during repeated tests. Balance index and hit delay were significantly smaller during the 4th and 5th than during the 1st test session (p < 0.05), but they did not change significantly between the other test sessions. The normative limit for side difference in postural control was 22%. VFP can be used to follow active postural control due to its high test-retest repeatability. However, learning effects in some parameters must be taken into account when applying VFP repeatedly in different patient populations to assess the progress in postural control.