Allan M. Rubin

Stabilometry in balance assessment of dizzy and normal subjects

Normal adults and patients referred to the Dizzy Clinic at the Medical College of Ohio had their standing balance assessed during combinations of normal and altered visual and somatosensory orientation conditions using a fixed-force platform to measure center-of-pressure translations. Significant differences were identified between normal subjects and dizzy patients, depending on the particular diagnostic category, the sensory condition tested, and the particular sway component being measured. Patients with central and peripheral vestibular dysfunctions had significantly greater sway than all other categories in most test conditions, especially with eyes closed and with a visual conflict dome while standing on a foam surface. The central vestibular dysfunction and peripheral vestibular dysfunction groups could be differentiated statistically under eyes-closed and visual conflict-foam conditions. The normal and psychogenic groups could not be differentiated statistically for any test conditions except one: there was significantly greater mean anterior/posterior sway displacement in the psychogenic group compared with all other diagnostic categories for the eyes-open foam test condition. Our results indicate that static stabilometry recordings of postural sway can be used to evaluate and quantify a dizzy patients ability to receive and process vestibular, visual, and somatosensory-proprioceptive cues for postural stability. It can also be used to monitor patients with vestibular disorders and to document their responses to rehabilitation programs.

Quantitative Changes of Amino Acid Distributions in the Rat Vestibular Nuclear Complex After Unilateral Vestibular Ganglionectomy

Abstract: Changes of amino acid concentrations in the vestibular nuclear complex (VNC) during lesion‐induced vestibular compensation were studied in rats after unilateral vestibular ganglionectomy. Distributions of 12 amino acids within the VNC were measured at 2, 4, 7, and 30 days after surgery, using microdissection of freeze‐dried brain sections and HPLC. Glutamate decreased on the lesioned side in nearly all VNC regions. Changes were fully developed 2 days after lesion and persisted through 30 days. In some regions, glutamate decreased also on the unlesioned side, especially at longer survival times, so that bilateral asymmetries became reduced. Aspartate changes were similar to those of glutamate on either side. Lesion‐induced glutamine asymmetry was usually opposite to that of glutamate. Although GABA concentration decreased at early survival times, it recovered at later times and sometimes increased in dorsal parts of lateral and medial nuclei. Taurine changes were similar to those of GABA in most regions. Glycine change was primarily limited to a bilateral decrease in the dorsal part of the lateral vestibular nucleus. Concentrations of other amino acids were much lower, but some showed postlesion changes.

Comparison of surgeries for removal of primary vestibular inputs: A combined anatomical and behavioral study in rats

Unilateral removal of Scarpas ganglion and neurectomy of the peripheral vestibular nerve branches were compared in rats as methods to eliminate primary vestibular input. Ocular nystagmus was consistently observed after both types of lesion, but it completely disappeared within 4 to 7 days. Imbalance and rotation were more serious and prolonged after ganglionectomy than after peripheral neurectomy. Corresponding with these differences in symptoms were differences in terminal degeneration. After ganglionectomy, degenerated axons and terminals were distributed throughout all terminal regions of primary vestibular fibers on the lesioned side, while after peripheral neurectomy, the degeneration was more limited. The results of this study suggest that vestibular ganglionectomy is a more successful approach than peripheral vestibular neurectomy for removing the primary vestibular input.

Spontaneous activity in rat vestibular nuclei in brain slices and effects of acetylcholine agonists and antagonists

Extracellular recording was used to investigate spontaneously active neurons in all four major nuclei of the rat vestibular nuclear complex (VNC) in brainstem slices. The density of spontaneously active neurons was highest in the medial vestibular nucleus (MVN), slightly lower in the superior (SuVN) and spinal (SpVN) nuclei, and lowest in the lateral vestibular nucleus (LVN). We compared the effects of acetylcholine agonists and antagonists on spontaneously discharging neurons in MVN, SuVN, and SpVN with those in the nearby dorsal cochlear nucleus (DCN). The proportion of neurons responding to carbachol was greatest in DCN and smallest in SpVN. Unlike in DCN, some neurons in MVN, SuVN, and SpVN showed decreased firing during carbachol or muscarine. Magnitudes of responses to carbachol and muscarine were closely correlated (P<0.01). MVN neurons possessed nicotinic as well as muscarinic receptors. Activation of either type was unaffected by blocking synaptic transmission. The IC(50) values for the muscarinic subtype-preferential antagonists were compared, and tropicamide, preferential for M(4), was the most potent. Our results suggest that: (1) the relative numbers of spontaneously active neurons in rat VNC differ among nuclei; (2) acetylcholine agonists elicit changes in mean firing rates of neurons in MVN, SuVN and SpVN, but fewer neurons respond, and responses are smaller than in DCN; (3) both muscarinic and nicotinic acetylcholine receptors are present on MVN neurons, but muscarinic receptors may be more prominent.

Quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding in rat vestibular nuclear complex after unilateral deafferentation, with comparison to cochlear nucleus

The distributions of non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the rat vestibular nuclear complex were estimated by quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding, respectively. The binding of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione in the vestibular nuclear complex was also compared with that in the cerebellar cortex and cochlear nucleus. Measurements were made in control rats and in rats with unilateral destruction of the inner ear and removal of the vestibular ganglion. Compared to the unlesioned side, 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione binding in the lesioned-side vestibular nuclear complex was decreased significantly in all regions at two to four postoperative days. However, the bilateral asymmetry disappeared in most regions by 30 days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding increased in the molecular layer of the cerebellar cortex at 30 days after lesion, although there were no clear changes at two to seven days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding in the cochlear nucleus decreased on the lesioned side, compared to the unlesioned side, in regions receiving significant auditory nerve innervation, but increased in the molecular layer of the dorsal cochlear nucleus. (+)-3-[3H]Dizocilpine maleate binding in regions of the vestibular nuclear complex was reduced on the lesioned side, compared to the unlesioned side, after deafferentation, with the largest reductions usually at 30 postoperative days. It is suggested that: (i) non-N-methyl-D-aspartate receptors are involved in synaptic transmission for both vestibular and auditory nerve fibers, while the involvement of N-methyl-D-aspartate receptors is less certain; (ii) unilateral deafferentation of the vestibular nuclear complex can result in bilateral asymmetries for non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors, which are most prominent at earlier and later survival times, respectively; and (iii) vestibular compensation may involve regulation of both non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the vestibular nuclear complex and activation of non-N-methyl-D-aspartate receptor-related processes in cerebellar cortex.

Head-Upright Tilt-Table Testing: A Useful Tool in the Evaluation and Management of Recurrent Vertigo of Unknown Origin Associated with Near-Syncope or Syncope

Recurrent idiopathic vertigo associated with near-syncope and syncope is a common perplexing problem, some cases of which are considered autonomically mediated (vasovagal). Upright-tilt-table testing has emerged as a potential method to test for vasovagal episodes. This study evaluated the use of this technique in the evaluation and management of patients with recurrent idiopathic vertigo associated with near-syncope or syncope. Twenty-one patients with recurrent unexplained vertigo and syncope/near-syncope and 11 control subjects were evaluated by use of an upright-tilt-table test for 30 minutes, with or without a graded isoproterenol infusion (1 to 4 μg/min given intravenously), in an attempt to provoke hypotension, bradycardia, or both, which reproduced the patients symptoms. The patients included 10 men and 11 women (mean age, 51 ± 16 years). Eleven controls with no history of vertigo were also studied. Transcranial Doppler sonography was used to assess cerebral arteriolar blood flow during tilt. All tilt-positive patients were placed on therapy with either β-blockers, disopyramide, or transdermal scopolamine, the effectiveness of which was determined with another tilt-table study. Symptoms occurred in seven patients (33%) during the baseline tilt and in eight patients (38%) during isoproterenol infusion (total positives, 71%). Transcranial Doppler sonography demonstrated a 225% ± 192% increase in pulsatility index and a 70% ± 29% increase in resistance index (indicative of cerebral arteriolar vasoconstriction) at the time of vertigo. No control subject experienced syncope during this test. Each tilt-positive patient eventually became tilt-negative with therapy, and over a mean follow-up period of 26 months, no further episodes have occurred. We conclude that head-upright tilt-table testing may be a valuable tool in the evaluation of recurrent idiopathic vertigo associated with near-syncope or syncope and in the evaluation of pharmacotherapy.

Quantitative distribution of amino acids in the rat vestibular nuclei.

The normal concentrations of 12 amino acids in the vestibular nuclei of rats were quantitatively measured using microdissection of freeze-dried brain sections combined with high performance liquid chromatography (HPLC) analysis. Both excitatory amino acids, aspartate and glutamate, showed only small variation across the vestibular nuclei. The distribution of glutamine tended to parallel that of glutamate. The inhibitory amino acids, gamma-aminobutyrate (GABA) and glycine, were much more concentrated in some regions than in others. GABA tended to be more concentrated than glycine in dorsal and rostral nuclei, while glycine tended to be more concentrated than GABA in ventral and caudal nuclei. The distribution of taurine was comparable to that of GABA, suggesting a close relationship with GABA function. Asparagine, serine, threonine, arginine, alanine and tyrosine had relatively low concentrations without significant differences among vestibular nuclei. Our results suggest that (1) different parts of the vestibular nuclear complex may receive similar amounts of excitatory amino acid afferents, (2) there is predominance of GABA or glycine as an inhibitory transmitter in different parts of the vestibular nuclear complex, and (3) there may be a close functional relationship between taurine and GABA within the vestibular nuclear complex. These results provide data basic to further research on the details of amino acid functions in the normal and abnormal vestibular system, as well as studies of plasticity in this system.

Effects of unilateral vestibular ganglionectomy on glutaminase activity in the vestibular nerve root and vestibular nuclear complex of the rat

The metabolism of glutamate, the most likely neurotransmitter of vestibular ganglion cells, includes synthesis from glutamine by the enzyme glutaminase. We used microdissection combined with a fluorometric assay to measure glutaminase activity in the vestibular nerve root and nuclei of rats with unilateral vestibular ganglionectomy. Glutaminase activity in the lesioned‐side vestibular nerve root decreased by 62% at 4 days after ganglionectomy and remained at similar values through 30 days. No change occurred in the contralateral vestibular nerve root. Glutaminase activity changes in the vestibular nuclei were lesser in magnitude and more complex, including contralateral increases as well as ipsilateral decreases. At 4 days after ganglionectomy, glutaminase activity was 10–20% lower in individual lesioned‐side nuclei compared with their contralateral counterparts. By 14 and 30 days after ganglionectomy, there were no statistically significant differences between the nuclei on the two sides. This transient asymmetry of glutaminase activities in the vestibular nuclei contrasts with the sustained asymmetry in the vestibular nerve root and suggests that intrinsic, commissural, or descending pathways are involved in the recovery of chemical symmetry. This recovery resembles our previous finding for glutamate concentrations in the vestibular nuclei and may partially underlie central vestibular compensation after peripheral lesions.

Astrocyte Reaction in the Rat Vestibular Nuclei after Unilateral Removal of Scarpa's Ganglion

Unilateral vestibular ganglionectomy (UVG) results in a complete degeneration of vestibular nerve fibers and terminals in the ipsilateral vestibular nuclear complex (VNC). A subsequent glial reaction may affect the activities of VNC neurons and thereby influence compensation for lesion-induced vestibular disorders. Expression of glial fibrillary acidic protein (GFAP), a specific marker for reactive astrocytes, was demonstrated immunohistochemically in the rat VNC at 7, 14, and 35 days after UVG. An increased GFAP-positive astrocytic response was evident at 7 days after lesion in all the VNC regions on the lesioned side and in some regions on the unlesioned side and remained through 35 days. The glial response included hypertrophy, which was more prominent at 7 days than at 14 days or 35 days, and proliferation, more prominent at the later times, of GFAP-positive astrocytes. Astrocytic projections around VNC neuron somata and proximal dendrites increased in number and became thicker and more elongated, especially at 14 days, in the lateral vestibular nucleus. It is suggested that UVG results in a bilateral astrocytic reaction in the VNC that would affect the subsequent compensation.

The assessment and management of the dizzy patient

A significant number of individuals are affected by symptoms of dizziness. It is the most common complaint among patients over 75 years of age. A large number of these patients seek counsel from their physicians. It is imperative for the evaluating physician to obtain a thorough history and perform a complete physical exam. The proper diagnostic studies must also be obtained to confirm or rule out particular diagnoses. The physician should never assume that the dizziness is the result of normal aging prior to ruling out pathologic conditions.