G.M. Halmagyi

Head taps evoke a crossed vestibulo-ocular reflex

Taps to the forehead on the midline, at the hairline (Fz), with a reflex hammer or powerful bone conduction vibrator caused short-latency surface potentials from beneath both eyes in all healthy subjects. The earliest negative responses were invariably absent from the eye contralateral to the side of a previous vestibular nerve section but were preserved despite sensorineural hearing loss. These responses probably reflect vestibular function via crossed otolith–ocular pathways.

Transverse Sinus Stenting for Idiopathic Intracranial Hypertension: A Review of 52 Patients and of Model Predictions

Current thinking is that transverse sinus stenosis with significant pressure gradient across the narrowing may play a role in pseudotumor cerebri and that treatment may improve symptoms. Here, the authors review their experience with 52 patients who were clinically followed for 2–8 months after stenting. During this time all pressure gradients improved and symptoms were abolished. Symptom relapse occurred in 6 patients and all showed sinus restenosis. At the end of the study period, 49 of 52 patients were cured of their headaches and the authors concluded that transverse sinus stenting is beneficial in this clinical setting. BACKGROUND AND PURPOSE: Transverse sinus stenosis is common in patients with IIH. While the role of transverse sinus stenosis in IIH pathogenesis remains controversial, modeling studies suggest that stent placement within a transverse sinus stenosis with a significant pressure gradient should decrease cerebral venous pressure, improve CSF resorption in the venous system, and thereby reduce intracranial (CSF) pressure, improving the symptoms of IIH and reducing papilledema. We aimed to determine if IIH could be reliably treated by stent placement in transverse sinus stenosis. MATERIALS AND METHODS: We reviewed the clinical, venographic, and intracranial pressure data before and after stent placement in transverse sinus stenosis in 52 of our own patients with IIH unresponsive to maximum acceptable medical treatment, treated since 2001 and followed between 2 months and 9 years. RESULTS: Before stent placement, the mean superior sagittal sinus pressure was 34 mm Hg (462 mm H20) with a mean transverse sinus stenosis gradient of 20 mm Hg. The mean lumbar CSF pressure before stent placement was 322 mm H2O. In all 52 patients, stent placement immediately eliminated the TSS pressure gradient, rapidly improved IIH symptoms, and abolished papilledema. In 6 patients, symptom relapse (headache) was associated with increased venous pressure and recurrent stenosis adjacent to the previous stent. In these cases, placement of another stent again removed the transverse sinus stenosis pressure gradient and improved symptoms. Of the 52 patients, 49 have been cured of all IIH symptoms. CONCLUSIONS: These findings indicate a role for transverse sinus stent placement in the management of selected patients with IIH.

Benign positional nystagmus A study of its three-dimensional spatio-temporal characteristics

Objective: To describe the spatial and temporal characteristics of benign positional nystagmus (BPN) subtypes in benign positional vertigo (BPV) due to vestibular lithiasis affecting one or more semicircular canals (SCCs). Background: Activation of SCC receptors by sequestered otoconia, either freely moving (canalithiasis) or cupula-adherent (cupulolithiasis) during head position changes with respect to gravity, is the accepted cause of BPV. Although accurate identification and interpretation of BPN is critical to BPV therapy, no rigorous, kinematically correct three-dimensional spatio-temporal analysis of BPN in all its forms exists. Methods: Using dual-search scleral coils, the authors recorded BPN provoked by Dix–Hallpike or supine ear-down test in a two-axis whole-body rotator in 44 patients with refractory BPV. To localize the SCC affected, BPN rotation axes were compared to SCC axes, axes orthogonal to average SCC planes. Results: Sixteen patients had upbeat, geotropic-torsional BPN in the Dix–Hallpike test to one side and five to both sides, with BPN rotation axes clustered around the lowermost posterior SCC axis. Seven had direction-changing horizontal BPN, three geotropic (canalithiasis) and four apogeotropic (cupulolithiasis), with rotation axes around the lowermost and uppermost horizontal SCC axis. Seven had predominantly downbeating BPN with rotation axes clustered around one superior SCC axis. Nine had upbeat, horizontal-torsional BPN with rotation axes located between posterior and horizontal SCC axes of the lowermost ear suggesting simultaneous lithiasis in both SCCs. BPN vector-guided repositioning therapy was successful in 43 patients. Conclusion: Benign positional vertigo can affect one or more semicircular canals and three-dimensional recording with vector analysis of the benign positional nystagmus (BPN) can guide canalith repositioning therapy especially in refractory cases with atypical BPN.

Horizontal head impulse test detects gentamicin vestibulotoxicity

Background: Parenteral antibiotic therapy with gentamicin, even in accepted therapeutic doses, can occasionally cause bilateral vestibular loss (BVL) due to hair cell toxicity. Objective: To quantify in patients with gentamicin vestibulotoxicity (GVT) the extent of acceleration gain deficit of the horizontal vestibulo-ocular reflex at different accelerations with a graded head impulse test (HIT) in comparison with standard caloric and rotational testing. To characterize the corresponding HIT catch-up saccade pattern to provide the basis for its salience to clinicians. Methods: Horizontal HIT of graded acceleration (750°–6,000°/sec2) was measured with binocular dual search coils in 14 patients with GVT and compared with 14 normal subjects and a control subject with total surgical BVL. Results: Patients showed mostly symmetric HIT gain deficits with a continuous spectrum from almost normal to complete BVL. Gain deficits were present even at the lowest head accelerations. HIT gain correlated better with caloric (Spearman ρ = 0.85, p = 0.0001) than rotational testing (ρ = 0.55, p = 0.046). Cumulative amplitude of overt saccades after head impulses was 5.6 times larger in patients than in normal subjects. Compared with previously published patients after unilateral vestibular deafferentation, GVT patients with BVL generated only approximately half the percentage of covert saccades during head rotation (23% at 750°/sec2 to 46% at 6,000°/sec2). Conclusions: Head impulse testing is useful for early bedside detection of gentamicin vestibulotoxicity because most patients, even those with partial bilateral vestibular loss (BVL), have large overt saccades. Covert saccades, which can conceal the extent of BVL, are only approximately half as frequent as in unilateral patients, but may be present even in total BVL.

Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome

Objective: The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features. Methods: Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia. Results: The reported age at onset range was 39–71 years, and symptom duration was 3–38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared. Conclusions: Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS).

The click-evoked vestibulo-ocular reflex in superior semicircular canal dehiscence

The authors studied eye movement responses to loud (110dB) clicks in 4 patients with Tullio effect due to superior semicircular canal dehiscence and in 9 normal subjects, by averaging the electro-oculogram. All 4 patients had small (0.1–0.3 deg) but easily reproducible vertical vestibulo-ocular reflex eye movement responses to the clicks. Normal subjects had responses that were at least 10 times smaller. The click-evoked vestibulo-ocular reflex test is a simple, robust way to screen dizzy patients for symptomatic superior semicircular dehiscence.

Gentamicin ototoxicity: a 23-year selected case series of 103 patients

Objective: To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital.

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patients clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

Gentamicin vestibulotoxicity impairs human electrically evoked vestibulo-ocular reflex.

Background: Electrical vestibular stimulation is believed to directly activate the vestibular afferents to mediate an electrically evoked vestibulo-ocular reflex (eVOR). Gentamicin, an aminoglycoside antibiotic, induces vestibulotoxicity by hair cell damage and death. Objective: To determine if human eVOR is impaired by hair cell damage and death in systemic gentamicin vestibulotoxicity (GV). Methods: Three-dimensional binocular eye movements evoked by bilateral, bipolar, 100 msec direct current-step at intensities of 0.9, 2.5, 5.0, 7.5, and 10.0 mA were recorded with dual-search coils in 12 GV patients, and the results were compared to 13 healthy subjects. Results: Normal eVOR was predominantly torsional, comprising phasic eVOR initiation and cessation acceleration pulses at 9 msec latency after current onset and offset, with a tonic eVOR velocity-step during the 100 msec intervening period of maintained current. Normal phasic eVOR increased, while tonic eVOR scaled linearly, with current intensity. GV impaired phasic eVOR more severely than tonic eVOR, and prolonged the latency to 12–13 msec. In patients without mechanical response to vestibular tests, phasic eVOR was reduced to one-fifth of normal amplitude, doubled in duration, had reduced ability to vary with current intensity, and threshold was increased. Tonic eVOR was reduced to one-third of normal, but still scaled linearly with current intensity. Patients, who retained partial mechanical responses to vestibular tests, had phasic eVOR impairment without tonic eVOR abnormality. Conclusion: Impairment of evoked vestibulo-ocular reflex (eVOR) in gentamicin vestibulotoxicity (GV) suggests that vestibular hair cells, activated by electrical stimulation, mediate the eVOR. Abnormalities of the eVOR, especially the phasic component, might be a marker of vestibular injury in GV. GLOSSARY: eVOR = electrically evoked vestibulo-ocular reflex; EVS = electrical (galvanic) vestibular stimulation; GV = gentamicin vestibulotoxicity.

Click-evoked vestibulo-ocular reflex: Stimulus–response properties in superior canal dehiscence

Background: An enlarged, low-threshold click-evoked vestibulo-ocular reflex (VOR) can be averaged from the vertical electro-oculogram in a superior canal dehiscence (SCD), a temporal bone defect between the superior semicircular canal and middle cranial fossa. Objective: To determine the origin and quantitative stimulus–response properties of the click-evoked VOR. Methods: Three-dimensional, binocular eye movements evoked by air-conducted 100-microsecond clicks (110 dB normal hearing level, 145 dB sound pressure level, 2 Hz) were measured with dual-search coils in 11 healthy subjects and 19 patients with SCD confirmed by CT imaging. Thresholds were established by decrementing loudness from 110 dB to 70 dB in 10-dB steps. Eye rotation axis of click-evoked VOR computed by vector analysis was referenced to known semicircular canal planes. Response characteristics were investigated with regard to enhancement using trains of three to seven clicks with 1-millisecond interclick intervals, visual fixation, head orientation, click polarity, and stimulation frequency (2 to 15 Hz). Results: In subjects and SCD patients, click-evoked VOR comprised upward, contraversive-torsional eye rotations with onset latency of approximately 9 milliseconds. Its eye rotation axis aligned with the superior canal axis, suggesting activation of superior canal receptors. In subjects, the amplitude was less than 0.01°, and the magnitude was less than 3°/second; in SCD, the amplitude was up to 60 times larger at 0.66°, and its magnitude was between 5 and 92°/second, with a threshold 10 to 40 dB below normal (110 dB). The click-evoked VOR magnitude was enhanced approximately 2.5 times with trains of five clicks but was unaffected by head orientation, visual fixation, click polarity, and stimulation frequency up to 10 Hz; it was also present on the surface electro-oculogram. Conclusion: In superior canal dehiscence, clicks evoked a high-magnitude, low-threshold, 9-millisecond-latency vestibulo-ocular reflex that aligns with the superior canal, suggesting superior canal receptor hypersensitivity to sound.