John S Stahl

Publications (32)108.53 Total impact

• Article: 4-aminopyridine does not enhance flocculus function in tottering, a mouse model of vestibulocerebellar dysfunction and ataxia.

  John S Stahl, Zachary C Thumser
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  ABSTRACT: The potassium channel antagonist 4-aminopyridine (4-AP) improves a variety of motor abnormalities associated with disorders of the cerebellum. The most rigorous quantitative data relate to 4-AP's ability to improve eye movement deficits in humans referable to dysfunction of the cerebellar flocculus. Largely based on work in the ataxic mouse mutant (which carries a mutation of the Cacna1a gene of the P/Q voltage-activated calcium channel), 4-AP is hypothesized to function by enhancing excitability or rhythmicity of floccular Purkinje cells. We tested this hypothesis by determining whether systemic or intrafloccular administration of 4-AP would ameliorate the eye movement deficits in that are attributable to flocculus dysfunction, including the reductions in amplitude of the yaw-axis vestibulo-ocular reflex (VOR) and vision-enhanced vestibulo-ocular reflex (VVOR), and the optokinetic reflex (OKR) about yaw and roll axes. Because deficits increase with age, both young and elderly mutants were tested to detect any age-dependent 4-AP effects. 4-AP failed to improve VOR, VVOR, and OKR gains during sinusoidal stimuli, although it may have reduced the tendency of the mutants' responses to VOR and VVOR to decline over the course of a one-hour recording session. For constant-velocity optokinetic stimuli, 4-AP generated some enhancement of yaw OKR and upward-directed roll OKR, but the effects were also seen in normal C57BL/6 controls, and thus do not represent a specific reversal of the electrophysiological consequences of the mutation. Data support a possible extra-floccular locus for the effects of 4-AP on habituation and roll OKR. Unilateral intrafloccular 4-AP injections did not affect ocular motility, except to generate mild eye elevations, consistent with reduced floccular output. Because 4-AP did not produce the effects expected if it normalized outputs of floccular Purkinje cells, there is a need for further studies to elucidate the drug's mechanism of action on cerebellar motor dysfunction.
  PLoS ONE 01/2013; 8(2):e57895. · 4.09 Impact Factor
• Article: Handheld cellular phones restrict head movements and range of visual regard.

  Zachary C Thumser, John S Stahl
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  ABSTRACT: Numerous studies have reported the ability of mobile phones to distract users and thereby degrade performance of concurrent tasks. Less is known about whether the phone-holding posture can itself influence concurrent motor activities. Horizontal eye movements are often coordinated with head movements, particularly when the amplitude of the gaze shift is large. Holding a phone to one ear has been shown to restrict the range of spontaneously generated head movements. In order to determine whether the phone-holding posture also influences gaze, we recorded eye and head movements as volunteers looked about themselves spontaneously. Holding the phone to the ear narrowed the range of gaze, principally in subjects who exhibit a strong propensity to move the head with the eyes. We argue that visual exploration may be influenced by the balance between costs and benefits of turning the head, with the phone-holding posture increasing the costs. The effects on gaze would be seen most clearly in subjects who have a higher predilection for coupling eye and head movements. Conversely, this effect would be minimal if tested in tasks that rarely elicit head movements in the specific subjects being tested. The results emphasize the close coordination between eye and head movements, and have implications for the design of ergonomic studies comparing the effects of handheld vs. hands-free mobile phones on performance of specific tasks, such as driving.
  Human movement science 12/2012; · 2.15 Impact Factor
• Article: Dynamics of Abducens Nucleus Neurons in the Awake Mouse.

  John S Stahl, Zachary C Thumser
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  ABSTRACT: The mechanics of the eyeball and orbital tissues (the "ocular motor plant") are a fundamental determinant of ocular motor signal processing. The mouse is used increasingly in ocular motor physiology, but little is known about its plant mechanics. One way to characterize the mechanics is to determine relationships between extraocular motoneuron firing and eye movement. We recorded abducens nucleus neurons in mice executing compensatory eye movements during 0.1-1.6 Hz oscillation in the light. We analyzed firing rates to extract eye position and eye velocity sensitivities, from which we determined time constants of a viscoelastic model of the plant. The majority of abducens neurons were already active with the eye in its central rest position, with only 6% recruited at more abducted positions. Firing rates exhibited largely linear relationships to eye movement, although there was a nonlinearity consisting of increasing modulation in proportion to eye movement as eye amplitudes became small (due to reduced stimulus amplitude or reduced alertness). Eye position and velocity sensitivities changed with stimulus frequency as expected for an ocular motor plant dominated by cascaded viscoelasticities. Transfer function poles lay at approximately 0.1 and 0.9s. In comparison to previously studied animal species, the mouse plant is stiffer than the rabbit, but laxer than cat and rhesus. Differences between mouse and rabbit can be explained by scaling for eye size (allometry). Differences between the mouse and cat or rhesus can be explained by differing ocular motor repertoires of animals with and without a fovea or area centralis.
  Journal of Neurophysiology 08/2012; · 3.32 Impact Factor
• Article: The ataxic mouse as a model for studying downbeat nystagmus.

  John S Stahl, Zachary C Thumser, Brian S Oommen
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  ABSTRACT: Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice.
  Journal of Vestibular Research 01/2012; 22(5):221-41. · 1.35 Impact Factor
• Article: Crossover trial of gabapentin and memantine as treatment for acquired nystagmus.

  Matthew J Thurtell, Anand C Joshi, Alice C Leone, Robert L Tomsak, Gregory S Kosmorsky, John S Stahl, R John Leigh
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  ABSTRACT: We conducted a masked, crossover, therapeutic trial of gabapentin (1,200mg/day) versus memantine (40 mg/day) for acquired nystagmus in 10 patients (aged 28-61 years; 7 female; 3 multiple sclerosis [MS]; 6 post-stroke; 1 post-traumatic). Nystagmus was pendular in 6 patients (4 oculopalatal tremor; 2 MS) and jerk upbeat, hemi-seesaw, torsional, or upbeat-diagonal in each of the others. For the group, both drugs reduced median eye speed (p < 0.001), gabapentin by 32.8% and memantine by 27.8%, and improved visual acuity (p < 0.05). Each patient improved with 1 or both drugs. Side effects included unsteadiness with gabapentin and lethargy with memantine. Both drugs should be considered as treatment for acquired forms of nystagmus.
  Annals of Neurology 05/2010; 67(5):676-80. · 11.09 Impact Factor
• Article: Probing the mechanism of saccade-associated head movements through observations of head movement propensity and cognition in the elderly.

  Zachary C Thumser, Nancy L Adams, Alan J Lerner, John S Stahl
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  ABSTRACT: Humans may accomplish gaze shifts by eye-only saccades or combined eye-head saccades. The mechanisms that determine whether the head moves remain poorly understood. Many observations can be explained if phylogenetically ancient circuits generate eye-head saccades by default and frontal cerebral structures interrupt this synergy when eye-only saccades are preferable. Saccade-associated head movements have been reported to increase in the elderly. To test the hypothesis of frontal inhibition of head movements, we investigated whether the increase is associated with a decline in frontal cognitive function. We measured head movement tendencies and cognition in volunteers aged 61-80. Measures of head movement tendency included the customary range of eye eccentricity, customary range of head eccentricity, range of target eccentricities evoking predominantly eye-only saccades, and two measures of head amplitude variation as a function of target eccentricity. Cognitive measures encompassed verbal fluency, verbal memory, non-verbal memory, and executive function. There was no correlation between cognition and any measure of head movement tendency. We combined these elderly data with measurements of head movements in a group aged 21-67 and found mildly reduced, not increased, head movement tendencies with age. However, when confronted with a task that could be accomplished without moving the head, young subjects were more likely to cease all head movements. While inconclusive regarding the hypothesis of inhibition of saccade-associated head movements by cerebral structures, the results indicate the need to distinguish between mechanisms that define head movement tendencies and mechanisms that adapt head motion to the geometry of a specific task.
  Experimental Brain Research 03/2010; 202(4):903-13. · 2.39 Impact Factor
• Article: An altered phenotype in a conditional knockout of Pitx2 in extraocular muscle.

  Yuefang Zhou, Georgiana Cheng, Lisa Dieter, Tord A Hjalt, Francisco H Andrade, John S Stahl, Henry J Kaminski
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  ABSTRACT: To determine the temporal and spatial expression of Pitx2, a bicoid-like homeobox transcription factor, during postnatal development of mouse extraocular muscle and to evaluate its role in the growth and phenotypic maintenance of postnatal extraocular muscle. Mouse extraocular muscles of different ages were examined for the expression of Pitx2 by RT-PCR, q-PCR, and immunostaining. A conditional mutant mouse strain, in which Pitx2 function is inactivated at postnatal day (P)0, was generated with a Cre-loxP strategy. Histology, immunostaining, real-time PCR, in vitro muscle contractility, and in vivo ocular motility were used to study the effect of Pitx2 depletion on extraocular muscle. All three Pitx2 isoforms were expressed by extraocular muscle and at higher levels than in other striated muscles. Immunostaining demonstrated the presence of Pitx2 mainly in extraocular muscle myonuclei. However, no obvious expression patterns were observed in terms of anatomic region (orbital versus global layer), innervation zone, or muscle fiber types. The mutant extraocular muscle had no obvious pathology but had altered muscle fiber sizes. Expression levels of myosin isoforms Myh1, Myh6, Myh7, and Myh13 were reduced, whereas Myh2, Myh3, Myh4, and Myh8 were not affected by postnatal loss of Pitx2. In vitro, Pitx2 loss made the extraocular muscles stronger, faster, and more fatigable. Eye movement recordings found saccades to have a lower peak velocity. Pitx2 is important in maintaining the mature extraocular muscle phenotype and regulating the expression of critical contractile proteins. Modulation of Pitx2 expression can influence extraocular muscle function with long-term therapeutic implications.
  Investigative ophthalmology & visual science 05/2009; 50(10):4531-41. · 3.43 Impact Factor
• Article: Eye orientation during static tilts and its relationship to spontaneous head pitch in the laboratory mouse.

  Brian S Oommen, John S Stahl
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  ABSTRACT: Both eye position and head orientation are influenced by the macular (otolith) organs, via the tilt maculo-ocular reflex (tiltMOR) and the vestibulo-collic reflexes, respectively. The mechanisms that control head position also influence the rest position of the eye because head orientation influences eye position through the tiltMOR. Despite the increasing popularity of mice for studies of vestibular and ocular motor functions, relatively little is known in this species about tiltMOR, spontaneous orientation of the head, and their interrelationship. We used 2D video oculography to determine in C57BL/6 mice the absolute horizontal and vertical positions of the eyes over body orientations spanning 360 degrees about the pitch and roll axes. We also determined head pitch during ambulation in the same animals. Eye elevation varied approximately sinusoidally as functions of pitch or roll angle. Over the central +/-30 degrees of pitch, sensitivity and gain in the light were 31.7 degrees/g and 0.53, respectively. The corresponding values for roll were 31.5 degrees/g and 0.52. Absolute positions adopted in light and darkness differed only slightly. During ambulation, mice carried the lambda-bregma plane at a downward pitch of 29 degrees , corresponding to a horizontal eye position of 64 degrees and a vertical eye position of 22 degrees . The vertical position is near the center of the range of eye movements produced by the pitch tiltMOR. The results indicate that the tiltMOR is robust in this species and favor standardizing pitch orientation across laboratories. The robust tiltMOR also has significant methodological implications for the practice of pupil-tracking video oculography in this species.
  Brain Research 03/2008; 1193:57-66. · 2.73 Impact Factor
• Article: Eye hyperdeviation in mouse cerebellar mutants is comparable to the gravity-dependent component of human downbeat nystagmus.

  John S Stahl, Brian S Oommen
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  ABSTRACT: Humans with cerebellar degeneration commonly exhibit downbeat nystagmus (DBN). DBN has gravity-independent and -dependent components, and the latter has been proposed to reflect hyperactive tilt maculo-ocular reflexes (tilt-MOR). Mice with genetically determined cerebellar ataxia do not exhibit DBN, but they do exhibit tonic hyperdeviation of the eyes, which we have proposed to be the DBN equivalent. As such, the tilt-MOR might be predicted to be hyperactive in these mutant mice. We measured the tilt-MOR in 10 normal C57BL/6 mice and in 6 tottering, a mutant exhibiting ataxia and ocular motor abnormalities due to mutation of the P/Q calcium channel. Awake mice were placed in body orientations spanning 360 degrees about the pitch axis. The absolute, equilibrium vertical angular deviations of one eye were measured using infrared videooculography. In both strains, eye elevation varied quasi-sinusoidally with tilt angle in the range of 90 degrees nose-up to 90 degrees nose-down. Beyond this range the eye returned to a neutral position. Deviation over +/-30 degrees of tilt was an approximately linear function of the projection of the gravity vector into the animal's horizontal plane, and can thus be summarized by its slope (sensitivity). Sensitivity measured 14.9 degrees/g for C57BL/6 and 20.3 degrees/g for tottering, a statistically significant difference. Thus the pitch otolithic reflex of the ataxic mutants is hyperactive relative to controls and could explain tonic hyperdeviation of the eyes, consistent with the idea that the tonic hyperdeviation is analogous to DBN.
  Progress in brain research 02/2008; 171:503-8. · 3.04 Impact Factor
• Article: Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging.

  John S Stahl, Robert A James, Brian S Oommen, Freek E Hoebeek, Chris I De Zeeuw
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  ABSTRACT: Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.
  Journal of Neurophysiology 04/2006; 95(3):1588-607. · 3.32 Impact Factor
• Article: Saccadic Palsy after Cardiac Surgery

  ROBERT L. TOMSAK, BRUCE T. VOLPE, JOHN S. STAHL, R. JOHN LEIGH
  Annals of the New York Academy of Sciences 01/2006; 956(1):430 - 433. · 3.15 Impact Factor
• Article: Saccadic and Vestibular Abnormalities in Multiple Sclerosis

  DEBORAH L. DOWNEY, JOHN S. STAHL, ROONGROJ BHIDAYASIRI, JOY DERWENSKUS, NANCY L. ADAMS, ROBERT L. RUFF, R. JOHN LEIGH
  Annals of the New York Academy of Sciences 01/2006; 956(1):438 - 440. · 3.15 Impact Factor
• Article: Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility.

  Hang Yin, John S Stahl, Francisco H Andrade, Colleen A McMullen, Sarah Webb-Wood, Nancy J Newman, Valerie Biousse, Douglas C Wallace, Machelle T Pardue
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  ABSTRACT: The adenine nucleotide transporter 1 gene (ANT1) encodes an inner mitochondrial membrane protein that transports ATP into the cell. Mutations within ANT1 produce a syndrome of chronic progressive external ophthalmoplegia (CPEO) in humans. Ant1 knockout (Ant1-/-) mice develop cardiomyopathy and mitochondrial myopathy of limb muscles. Because the extraocular muscles (EOM) are preferentially affected in human CPEO, the objective of this study was to determine whether Ant1-/- mice also exhibit an EOM mitochondrial myopathy. ANT isoform expression of isolated EOMs, EOM morphology and mitochondrial content, mitochondrial structure and function, ocular motility in intact mice, and contractile performance in isolated muscle preparations were examined. Ant1-/- EOMs had the typical appearance of mitochondrial myopathy, including increase in mitochondrial size, number, and oxidative phosphorylation (OXPHOS) staining. However, there were no measurable ocular motor abnormalities in intact Ant1-/- mice, and their isolated EOMs did not show evidence of increased fatigability. EOMs of wild-type mice exhibited higher levels of Ant2 mRNA compared with hindlimb muscle, which may compensate for the Ant1 loss in mutant mouse EOMs and account for the normal EOM function. The Ant1-/- mice provide a model in which to study CPEO pathology and compensatory mechanisms.
  Investigative Ophthalmology &amp Visual Science 01/2006; 46(12):4555-62. · 3.60 Impact Factor
• Article: Amplitudes of head movements during putative eye-only saccades.

  Brian S Oommen, John S Stahl
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  ABSTRACT: The mechanisms allowing humans and other primates to dissociate head and eye movements during saccades are poorly understood. A more precise knowledge of head movement behavior during apparent eye-only saccades may provide insight into those mechanisms. We studied the distributions of head amplitude in normal humans. In half of the subjects, these distributions indicated the presence of a population of minor ("residual") head movements during eye-only saccades, distinct from the continuum of head movements generated during frank eye-head saccades. Like full-sized head movements, the residual movements grew in proportion to target eccentricity, indicating their drive is derived from the premotor command for the saccade. Furthermore, their amplitudes related most strongly to the head amplitudes obtained when subjects produced full-sized head movements and were reduced when subjects were instructed to perform exclusively eye-only saccades. Both observations suggest that the drive for residual head movements originates downstream of the point in which the head movement command diverges from the generalized gaze shift command. The results are consistent with a model of head control in which a neural gate prevents the common gaze shift command from reaching the head premotor circuitry whenever an eye-only saccade is desired. However, the gate is either imperfect or the multiple pathways that relay gaze shift signals to the head motor circuitry allow for the gate to be circumvented. The results underscore the need for physiological studies to probe neuronal activity related to neck activation during eye-only saccades.
  Brain Research 01/2006; 1065(1-2):68-78. · 2.73 Impact Factor
• Article: Overlapping gaze shifts reveal timing of an eye-head gate.

  Brian S Oommen, John S Stahl
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  ABSTRACT: The ability to dissociate eye movements from head movements is essential to animals with foveas and fovea-like retinal specializations, as these species shift the eyes constantly, and moving the head with each gaze shift would be impractical and energetically wasteful. The processes by which the dissociation is effected remain unclear. We hypothesized that the dissociation is accomplished by means of a neural gate, which prevents a common gaze-shift command from reaching the neck circuitry when eye-only saccades are desired. We further hypothesized that such a gate would require a finite period to reset following opening to allow a combined eye-head saccade, and thus the probability of generating a head movement during a saccade would be augmented when a new visual target (the 'test' target) appeared during, or soon after, a combined eye-head saccade made to an earlier, 'conditioning' target. We tested human subjects using three different combinations of targets-a horizontal conditioning target followed by a horizontal test target (H/H condition), horizontal conditioning followed by vertical test (H/V), and vertical conditioning followed by horizontal test (V/H). We varied the delay between the onset of the conditioning head movement and the presentation of the test target, and determined the probability of generating a head movement to the test target as a function of target delay. As predicted, head movement probability was elevated significantly at the shortest target delays and declined thereafter. The half-life of the increase in probability averaged 740, 490, and 320 ms for the H/H, H/V, and V/H conditions, respectively. For the H/H condition, the augmentation appeared to outlast the duration of the conditioning head movement. Because the augmentation could outlast the conditioning head movement and did not depend on the head movements to the conditioning and test targets lying in the same directions, we could largely exclude the possibility that the augmentation arises from mechanical effects. These results support the existence of the hypothetical eye-head gate, and suggest ways that its constituent neurons might be identified using neurophysiological methods.
  Experimental Brain Research 12/2005; 167(2):276-86. · 2.39 Impact Factor
• Article: Inhibited head movements: a risk of combining phoning with other activities?

  Brian S Oommen, John S Stahl
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  ABSTRACT: Studies of cellular phone use while driving have attributed impaired performance to the distractions of conversation. We determined that holding an inactive phone to the ear reduces the probability of eccentric head positions, potentially indicating reduced ability to monitor the visual surround. This effect may constitute a risk of cellular phone use independent of conversation and peculiar to handheld models.
  Neurology 10/2005; 65(5):754-6. · 8.31 Impact Factor
• Article: Characterization of vestibular dysfunction in the mouse model for Usher syndrome 1F.

  Kumar N Alagramam, John S Stahl, Sherri M Jones, Karen S Pawlowski, Charles G Wright
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  ABSTRACT: The deaf-circling Ames waltzer (av) mouse harbors a mutation in the protocadherin 15 (Pcdh15) gene and is a model for inner ear defects associated with Usher syndrome type 1F. Earlier studies showed altered cochlear hair cell morphology in young av mice. In contrast, no structural abnormality consistent with significant vestibular dysfunction in young av mice was observed. Light and scanning electron microscopic studies showed that vestibular hair cells from presumptive null alleles Pcdh15(av-Tg) and Pcdh15(av-3J) are morphologically similar to vestibular sensory cells from control littermates, suggesting that the observed phenotype in these alleles might be a result of a central, rather than peripheral, defect. In the present study, a combination of physiologic and anatomic methods was used to more thoroughly investigate the source of vestibular dysfunction in Ames waltzer mice. Analysis of vestibular evoked potentials and angular vestibulo-ocular reflexes revealed a lack of physiologic response to linear and angular acceleratory stimuli in Pcdh15 mutant mice. Optokinetic reflex function was diminished but still present in the mutant animals, suggesting that the defect is primarily peripheral in nature. These findings indicate that the mutation in Pcdh15 results in either a functional abnormality in the vestibular receptor organs or that the defects are limited to the vestibular nerve. AM1-43 dye uptake has been shown to correlate with normal transduction function in hair cells. Dye uptake was found to be dramatically reduced in Pcdh15 mutants compared to control littermates, suggesting that the mutation affects hair cell function, although structural abnormalities consistent with significant vestibular dysfunction are not apparent by light and scanning electron microscopy in the vestibular neuroepithelia of young animals.
  Journal of the Association for Research in Otolaryngology 07/2005; 6(2):106-18. · 2.84 Impact Factor
• Article: Neural integrator function in murine CACNA1A mutants.

  John S Stahl, Robert A James
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  ABSTRACT: Time constants of gaze holding are shortened in rocker and tottering mice, two strains whose cerebellar dysfunction stems from genetic alterations of the P/Q calcium channel. The finding suggests that in mice as in primates, the cerebellum contributes to the function of the neural integrator. Studying CACNA1A mutants may elucidate how cerebellar signals support gaze holding.
  Annals of the New York Academy of Sciences 05/2005; 1039:580-2. · 3.15 Impact Factor
• Article: Internuclear ophthalmoparesis in episodic ataxia type 2.

  Janet C Rucker, Joanna Jen, John S Stahl, Nandhitha Natesan, Robert W Baloh, R John Leigh
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  ABSTRACT: Two patients sharing a novel mutation of the CACNA1A gene for P/Q calcium channels showed significant slowing of adducting saccades compared with normal subjects or patients with cerebellar disease. Internuclear ophthalmoparesis (INO) was clinically evident in one. While these findings might be specific to this mutation, INO in our patients with episodic ataxia type 2 suggested involvement outside the cerebellum, either in the brain-stem internuclear pathway or at the neuromuscular junction.
  Annals of the New York Academy of Sciences 05/2005; 1039:571-4. · 3.15 Impact Factor
• Article: Abnormal eye movements predict disability in MS: two-year follow-up.

  Joy Derwenskus, Janet C Rucker, Alessandro Serra, John S Stahl, Deborah L Downey, Nancy L Adams, R John Leigh
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  ABSTRACT: We conducted a two-year follow-up study of 40 patients with MS in whom we had reported that abnormal eye movements (AEM) were associated with greater general disability. AEM patients (17/40) remained significantly (p < .001) more disabled (median EDSS of 7.0) than those with normal eye movements (median EDSS of 5.0). AEM and great disability were associated with abnormal MRI signals in brainstem or cerebellum, where disease may involve control circuits for eye movements as well as descending motor pathways.
  Annals of the New York Academy of Sciences 04/2005; 1039:521-3. · 3.15 Impact Factor