Emeritus Faculty, Acad Council, Neurology & Neurological Sciences
Chief of Neurology, Santa Clara Valley Medical Center (1985 - 2009)
Honors & Awards
Lysia Fornia Award for Teaching Excellence, Department of Neurology, Stanford University School of Medicine (1991)
Neurology Clerkship Teaching Award, Department of Neurology, Stanford University School of Medicine (2004-2007, 2009)
BA, Stanford University, Psychology (1968)
MD (honors), University of Washington, Medicine (1972)
Current Research and Scholarly Interests
The response and recovery of human visual, eye movement and related cognitive systems after acquired neurological disorders is a main area of interest. Experimental designs combine human brain neurophysiology techniques with psychophysics methods. We currently use transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as probes to test the postulate that visual perceptual learning alters early visual cortex.
Independent Studies (5)
- Directed Reading in Neurology and Neurological Science
NENS 299 (Aut, Win, Spr, Sum)
- Early Clinical Experience in Neurology and Neurological Sciences
NENS 280 (Aut, Win, Spr, Sum)
- Graduate Research
NENS 399 (Aut, Win, Spr, Sum)
- Medical Scholars Research
NENS 370 (Aut, Win, Spr, Sum)
- Undergraduate Research
NENS 199 (Aut, Win, Spr, Sum)
- Directed Reading in Neurology and Neurological Science
Noninvasive peroneal sensory and motor nerve conduction recordings in the rabbit distal hindlimb: feasibility, variability and neuropathy measure.
2014; 9 (3)
The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans, but reports of distal peroneal nerve conduction studies were not identified with a literature search. Distal sensorimotor recordings may be useful for studying rabbit models of length-dependent peripheral neuropathy. Surface electrodes were adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle and the superficial peroneal nerve. The deep and superficial peroneal nerves were stimulated above the ankle and the common peroneal nerve was stimulated at the knee. The nerve conduction studies were repeated twice with a one-week intertest interval to determine measurement variability. Intravenous vincristine was used to produce a peripheral neuropathy. Repeat recordings measured the response to vincristine. A compound muscle action potential and a sensory nerve action potential were evoked in all rabbits. The compound muscle action potential mean amplitude was 0.29 mV (SD ± 0.12) and the fibula head to ankle mean motor conduction velocity was 46.5 m/s (SD ± 2.9). The sensory nerve action potential mean amplitude was 22.8 μV (SD ± 2.8) and the distal sensory conduction velocity was 38.8 m/s (SD ± 2.2). Sensorimotor latencies and velocities were least variable between two test sessions (coefficient of variation = 2.6-5.9%), sensory potential amplitudes were intermediate (coefficient of variation = 11.1%) and compound potential amplitudes were the most variable (coefficient of variation = 19.3%). Vincristine abolished compound muscle action potentials and reduced sensory nerve action potential amplitudes by 42-57% while having little effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible with surface recordings and stimulation. The evoked distal sensory potentials have amplitudes, configurations and recording techniques that are similar to humans and may be valuable for measuring large sensory fiber function in chronic models of peripheral neuropathies.
View details for DOI 10.1371/journal.pone.0092694
View details for PubMedID 24658286
View details for PubMedCentralID PMC3962448
Visual perceptual learning is similar across the extrafoveal central visual fields
RESTORATIVE NEUROLOGY AND NEUROSCIENCE
2009; 27 (3): 181-188
Visual perceptual learning occurs with the presentation of novel visual stimuli at retinal sites near the fovea to 20 degrees eccentricities. It was unclear if the magnitude and rate of visual learning were similar across the central visual fields or if visual learning decreased with increasing eccentricity. The robustness of learning across the visual fields may affect the magnitude of computer-aided visual recovery after visual brain injury. Therefore we determined if eccentricity was a factor that influenced perceptual learning.Subjects were trained to detect the presence or absence of a single line oriented differently (odd-element) from an array of lines that otherwise had the same orientation. The odd-element line was presented 3 degrees, 9 degrees or 18 degrees from fixation.Perceptual performance improved during training trials with a similar magnitude and similar learning curve slopes at all 3 eccentricities. Pre- and post-training performance improved to a similar magnitude at 3 vs 9 degrees in 4 of 4 subjects tested and at 9 degrees vs 18 degrees in 4 of 5 subjects. In the fifth subject there was no post-training improvement in performance at 18 degrees.Visual perceptual learning is similar across the extrafoveal central visual fields in almost all subjects.
View details for DOI 10.3233/RNN-2009-0468
View details for Web of Science ID 000267763500003
View details for PubMedID 19531873
Perceptual learning of line orientation modifies the effects of transcranial magnetic stimulation of visual cortex.
Experimental Brain Research
2005; 162: 23-34
View details for DOI 10.1007/s00221-004-2117-5
- Acute vestibular syndrome NEW ENGLAND JOURNAL OF MEDICINE 1998; 339 (10): 680-685
Tracing the timing of human analysis of motion and chromatic signals from occipital to temporo-parieto-occipital cortex: A transcranial magnetic stimulation study
1998; 38 (17): 2619-2627
In human visual analysis, the initial processing of motion and chromatic signals may be mediated by feed-forward pathways from striate cortex to segregated areas of extrastriate cortex. The time-course of occipital to temporo-parieto-occipital motion processing was unknown, as was the selectivity of the effect of transcranial magnetic stimulation (TMS) on motion processing. TMS delivered over occipital cortex degraded the discrimination of motion-defined form (MDF) in a discrete time window beginning 100-120 ms from the onset of the visual stimulus. Bilateral focal TMS delivered over the temporo-parieto-occipital junction (TPO) disrupted the discrimination of MDF in a time window beginning 20-40 ms later than the effect of TMS delivered over occipital cortex. Bilateral focal TMS delivered over TPO also degraded the discrimination of CDF, motion direction, and color.
View details for Web of Science ID 000074769900010
View details for PubMedID 12116707
TRANSCRANIAL MAGNETIC STIMULATION OF EXTRASTRIATE CORTEX DEGRADES HUMAN MOTION DIRECTION DISCRIMINATION
1994; 34 (16): 2115-2123
The human temporo-parieto-occipital junction is an extrastriate visual area that may mediate motion vision processing. We determined if transcranial magnetic stimulation (TMS) delivered over this extrastriate area would degrade motion discrimination, similar to the transient decrease in spatial acuity observed when TMS is delivered over striate cortex. TMS was delivered 50-250 msec after the onset of a brief, random dot, motion direction discrimination task or a spatial acuity task. TMS significantly reduced correct motion discrimination when delivered 100-150 msec after the random dot stimulus. During the same time window TMS did not significantly effect spatial acuity. TMS over the left extrastriate cortex reduced motion discrimination in both hemifields and its effect had a crude topographical organization. TMS safely perturbs extrastriate visual areas and may reveal the temporal sequence of higher perceptual processing.
View details for Web of Science ID A1994NZ96700006
View details for PubMedID 7941409
Correlation of median forearm conduction velocity with carpal tunnel syndrome severity
2007; 118 (4): 781-785
Median nerve entrapment neuropathy at the wrist can be accompanied by slowed motor conduction within the forearm. Existing studies conflict regarding a correlation between the severity of the entrapment neuropathy in carpal tunnel syndrome (CTS) and slowing of median motor nerve conduction velocity (MNCV) in the forearm. Here, it was asked if there is a correlation between markers of CTS severity and median forearm MNCV, and if there is an explanation for the preceding conflicting results.Median MNCV in the forearm was correlated with neurophysiologic markers of severity of a median neuropathy at the wrist in 91 hands from 64 patients with clinical and electrodiagnostic evidence of CTS.Median MNCV within the forearm segment was negatively correlated with the median nerve distal motor latency (r=-0.64, P<0.001, n=91) and positively correlated with the CMAP amplitude of the abductor pollicis brevis muscle (r=0.45, P<0.001, n=91). These correlations only occurred in patients with a prolonged median distal motor latency. Previous investigations that failed to find such correlations used variable or non-standardized methods or analyzed smaller numbers of patients.Slowing of median MNCV in the forearm is related to the severity of the entrapment of median motor fibers at the wrist.Slowed forearm median MNCV can be a marker of motor nerve injury at the wrist.
View details for DOI 10.1016/j.clinph.2006.12.011
View details for Web of Science ID 000245737200009
View details for PubMedID 17307388
Perceptual learning of line orientation modifies the effects of transcranial magnetic stimulation of visual cortex
EXPERIMENTAL BRAIN RESEARCH
2005; 162 (1): 23-34
Perceptual learning may be accompanied by physiological changes in early visual cortex. We used transcranial magnetic stimulation (TMS) to test the postulate that perceptual learning of a visual task initially performed at 60-65% accuracy strengthens visual processing in early visual cortex. Single pulse TMS was delivered to human occipital cortex at time delays of 70-154 ms after the onset of an odd-element, line orientation discrimination task. When TMS was delivered at a delay of 84 ms or later the accuracy of visual discrimination was transiently degraded in ten subjects. As visual performance in control trials without TMS improved with training, the absolute magnitude of TMS suppression of performance decreased in parallel. This result occurred both when TMS was delivered to broad areas of occipital cortex and when TMS was optimally delivered to early occipital cortex. No change in TMS suppression was observed when three new subjects were given feedback during an odd-element task that did not require substantial perceptual learning. Thus, perceptual learning improved visual performance and reduced TMS suppression of early visual cortex in parallel.
View details for DOI 10.1007/s00221-004-2117-5
View details for Web of Science ID 000227740400003
View details for PubMedID 15578168
Transcranial magnetic stimulation: Neurophysiological applications and safety
BRAIN AND COGNITION
2002; 50 (3): 366-386
TMS is a non-invasive tool for measuring neural conduction and processing time, activation thresholds, facilitation and inhibition in brain cortex, and neural connections in humans. It is used to study motor, visual, somatosensory, and cognitive functions. TMS does not appear to cause long-term adverse neurological, cardiovascular, hormonal, motor, sensory, or cognitive effects in healthy subjects. Single-pulse (<1Hz) TMS is safe in normal subjects. High frequency, high-intensity repetitive TMS (rTMS) can elicit seizures even in normal subjects. Safety guidelines for using rTMS have been published.
View details for Web of Science ID 000180058100004
View details for PubMedID 12480484
Partial peripheral motor nerve lesions induce changes in the conduction properties of remaining intact motoneurons
MUSCLE & NERVE
2001; 24 (5): 662-666
A partial injury or loss of peripheral motor axons is followed by compensatory sprouting of remaining intact motor axons in order to reinnervate muscle. Little is known, however, about the electrophysiologic properties proximally of these intact motoneurons and their axons following injury of neighboring motor axons. We studied the conduction properties of intact cat motor axons and motoneurons proximal to the site of a partial peripheral nerve section. Twelve weeks after the partial transection of the cat medial gastrocnemius motor nerve, there was a significant (7%) reduction in conduction velocity and a 13% prolongation in afterhyperpolarization half-decay time in the remaining intact motoneurons, compared with controls. Partial injury to motor nerves thus induces reactive electrophysiologic changes in the remaining intact motoneurons and their axons, perhaps associated with compensatory sprouting within partially denervated muscle.
View details for Web of Science ID 000168367100009
View details for PubMedID 11317276
The selectivity and timing of motion processing in human temporo-parieto-occipital and occipital cortex: a transcranial magnetic stimulation study
1999; 37 (2): 169-179
An extrastriate visual area near the human temporo parieto occipital junction (TPO) may selectively mediate motion processing, while contributing little to the perception of color or form. This TPO area may be the human analogue of the monkey middle temporal (MT or V5) and medial superior temporal (MST) extrastriate visual areas. The selectivity of the effect of transcranial magnetic stimulation (TMS) on motion processing was unknown, as was the timecourse of occipital to TPO motion processing. In the first experiment, unilateral TMS was delivered over TPO 50-250 ms after the onset of a random dot motion discrimination display that was presented in the right or left hemifield. TMS reduced the correct discrimination of motion direction only when it was delivered in a discrete time window 100-175 ms following the onset of the display. TMS did not significantly affect hemifield spatial acuity in the same time window. In the second experiment, bilateral TMS delivered over occipital cortex also degraded the discrimination of motion-defined form (MDF) in a discrete time window following the onset of a display presented foveally. Bilateral focal TMS delivered over TPO disrupted the discrimination of MDF in a time window beginning 20-40 ms later than the effect of TMS delivered over occipital cortex. Bilateral focal TMS delivered over TPO also degraded the discrimination of color-defined form, motion direction and color. TMS can trace the timing of visual processing from occipital to extrastriate visual areas.
View details for Web of Science ID 000078571800005
View details for PubMedID 10080374
Rapid-rate transcranial magnetic stimulation of human frontal cortex can evoke saccades under facilitating conditions
ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1997; 105 (3): 246-254
Rapid-rate transcranial magnetic stimulation (rTMS) of a localized area within premotor frontal cortex elicited short-latency, multistep eye movements during a double-step saccade task in 3 of 9 subjects. These evoked saccades occurred in 14-32% of trials when rTMS was delivered over premotor regions located 5-7 cm lateral and 2-4 cm anterior to the vertex. In trials without rTMS or when rTMS was delivered medial or posterior to these sites, multistep saccades occurred in less than 2% of trials. In two subjects, rTMS of the right premotor cortex evoked contraversive saccades. In a third subject, rTMS of the left premotor cortex evoked saccades whose trajectory depended on the direction of the double-step targets. The amplitude and likelihood of occurrence of evoked saccades varied between rTMS trials. The intervals between evoked saccades were proportional to the intervals between rTMS pulses delivered at 16, 20 or 25 Hz. rTMS did not elicit saccades during fixation on a stationary target or during straight-ahead gaze in darkness, suggesting that the double-step saccade task facilitated the activation of a discrete premotor area consistent with the human frontal eye fields.
View details for Web of Science ID A1997XF63700010
View details for PubMedID 9216494
Anticipatory smooth eye movements and predictive pursuit after unilateral lesions in human brain
EXPERIMENTAL BRAIN RESEARCH
1996; 110 (1): 111-116
Anticipatory smooth eye movements precede expected changes in target motion. It has been questioned whether anticipatory smooth eye movements are a component of the smooth pursuit system. Five subjects with unilateral brain lesions and five control subjects were tested with predictable double-ramp stimuli to determine whether these lesions have a similar effect on horizontal, visually guided smooth pursuit, anticipatory smooth eye movements, and the predictive component of smooth pursuit. All four subjects with a brain lesion involving the parietal or parietal-frontal lobe had parallel velocity asymmetries in all three forms of smooth eye movements, with lowest velocities toward the side of the lesion. A similar uniformity and magnitude of smooth eye movement directional asymmetries were not found in control subjects. Unidirectional attenuation of these three forms of smooth eye movements provides evidence that they are part of a unified smooth eye movement system.
View details for Web of Science ID A1996UU57900013
View details for PubMedID 8817262
Stationary and pursuit visual fixation share similar behavior
1996; 36 (5): 751-763
Stationary and pursuit fixation may involve different fixation mechanisms that are reflected by differences in saccadic reaction times (SRTs). Gap, Simultaneous, and Overlap interval paradigms provided three distinct SRT ranges for comparisons between these two viewing conditions. SRTs following pursuit fixation were longer than following stationary fixation, but were similarly affected by the interval paradigms. The SRT increase with smooth pursuit was largely explained by additional demands for programming oblique saccades. The paradigm dependent SRT relationships also persisted after timing cues were minimized. These results indicate that stationary and pursuit fixation have similar responses to different fixation paradigms and do not implicate the existence of multiple fixation processes.
View details for Web of Science ID A1996UA32500010
View details for PubMedID 8762304
PROLONGED CONFUSION WITH NOCTURNAL WANDERING ARISING FROM NREM AND REM-SLEEP - A CASE-REPORT
1995; 18 (9): 757-764
A 51-year-old man with Machado-Joseph disease had a 3-year history of prolonged confusion following nightly nocturnal wandering. Polysomnography with videotape monitoring revealed 19- to 120-minute sleepwalking episodes emerging from non-rapid eye movement (NREM) sleep and occasionally from rapid eye movement (REM) sleep, followed by 22-47 minutes of prolonged confusion and disorientation. The patient also had a periodic limb movement disorder and obstructive sleep apnea syndrome. Excessive daytime sleepiness was evident by results from the Epworth Sleepiness Scale and Multiple Sleep Latency Test. A sleep-deprived electroencephalogram (EEG) and a polysomnogram with an expanded EEG montage before and during these episodes revealed no epileptiform activity. A contrast-enhanced brain magnetic resonance imaging (MRI) scan demonstrated findings consistent only with Machado-Joseph disease. The patient improved with a combination of temazepam and carbidopa-levodopa.
View details for PubMedID 8638068
TRANSESOPHAGEAL ECHOCARDIOGRAPHIC FINDINGS IN STROKE SUBTYPES
1994; 25 (1): 23-28
Transesophageal echocardiography has a high yield for detecting potential cardiac sources of embolism in patients with clinical risk factors for cardioembolism or unexplained stroke. The yield in other stroke subtypes is unknown.We classified 145 consecutively admitted patients into stroke subtypes based on clinical findings, brain imaging, and carotid ultrasound. Both transesophageal and transthoracic echocardiography were performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous mitral valve.Transesophageal echocardiography documented at least one of these findings in 46% of the patients compared with an 8% yield on the transthoracic study (P = .002). The yield of transesophageal echocardiography was substantial in all stroke subgroups. Patients with clinical risk factors for cardiac embolism had the highest frequency of spontaneous echo contrast (P = .001). Atrial septal aneurysms were most frequent in patients with lacunar syndromes (P = .012), and interatrial shunts were common in all stroke subtypes.Transesophageal echocardiographic findings vary considerably between stroke subgroups.
View details for Web of Science ID A1994MP10600005
View details for PubMedID 8266377
PREDICTIVE SMOOTH PURSUIT EYE-MOVEMENTS NEAR ABRUPT CHANGES IN MOTION DIRECTION
1992; 32 (4): 675-689
The stimulus-response characteristics of predictive smooth pursuit eye movements near the time of predictable, abrupt changes in target motion direction were studied. Expectations about the speed and direction of target motion both before and after the direction change affected specific components of the predictive pursuit responses. We propose that, when the direction of target motion is expected to change, the cessation of motion in one direction and the initiation of motion in a new direction are separately anticipated and that predictive pursuit movements are summated responses to these two events.
View details for Web of Science ID A1992HL73000010
View details for PubMedID 1413552
DIFFERENTIAL-DIAGNOSIS OF CHOREIFORM TARDIVE-DYSKINESIA
JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
1991; 3 (3): 255-268
Orofacial dyskinesias and choreiform movements of limbs occur with moderate frequency among psychiatric patients. Abnormal involuntary movements are symptoms of a wide variety of neurological and medical disorders. For both therapeutic and medicolegal reasons, psychiatric patients should be thoroughly evaluated before being given the diagnosis of tardive dyskinesia. This review presents the differential diagnosis of disorders associated with orofacial and appendicular choreiform involuntary movements. In addition, this paper provides a guide to the clinical and laboratory evaluation of patients with these symptoms.
View details for Web of Science ID A1991GC87600003
View details for PubMedID 1821242
MEMORY-CONTINGENT SACCADES AND THE SUBSTANTIA-NIGRA POSTULATE FOR ESSENTIAL BLEPHAROSPASM
1991; 114: 295-307
Essential blepharospasm and cranial dystonia are related focal dystonias of unknown aetiology. Blepharospasm induced by acute dopamine depletion in parkinsonism restricts saccade initiation possibly via the substantia nigra pars reticulata (SNpr). If essential blepharospasm and cranial dystonia similarly restrict saccades, then a selective, somatotopically arranged pathway such as the SNpr may be involved. To test this possibility memory-contingent and visually-guided saccades were measured in patients with essential blepharospasm and cranial dystonia. The latency of both forms of saccades was either significantly prolonged or excessively variable, while the accuracy and peak velocity of these fast eye movements were similar to age-matched control subjects. Essential blepharospasm and cranial dystonia alter the initiation of saccadic eye movements. Subcortical brain regions or pathways where eyelid, saccade and cranial/cervical motor control are somatotopically approximated, such as the SNpr, may be involved in blepharospasm.
View details for Web of Science ID A1991EZ43800017
View details for PubMedID 1998888
MOTION PERCEPTION PROMINENCE ALTERS ANTICIPATORY SLOW EYE-MOVEMENTS
EXPERIMENTAL BRAIN RESEARCH
1989; 74 (3): 555-562
Perceived motion may be a stimulus for anticipatory slow eye movements. To test this possibility, the production of anticipatory slow eye movements in humans was studied using apparent motion stimuli. Short range apparent motion was produced with random dot stimuli and the anticipatory slow eye movements were isolated from the smooth pursuit responses by occasionally including trials in which the random dot stimulus did not appear. Long range apparent motion was produced with subjective contour stimuli. Both short range and long range apparent motion were found to be effective stimuli for anticipatory slow eye movements. The prominence of perceived motion was altered by changing the spatiotemporal displacement intervals in the short range apparent motion stimuli. Changing the subjective contours also changed the motion percepts of the long range apparent motion stimuli. With both stimuli, the peak anticipatory slow eye velocities that were achieved decreased as the prominence of the motion percepts decreased, while the time-course of the anticipatory responses were similar under the different conditions. These findings indicate that the expectation of perceived motion is necessary for anticipatory slow eye movements.
View details for Web of Science ID A1989T433300012
View details for PubMedID 2707330
VERTICAL AND HORIZONTAL SACCADES IN AGING AND DEMENTIA - FAILURE TO INHIBIT ANTICIPATORY SACCADES
1988; 8 (5): 267-273
View details for Web of Science ID A1988Q985400007
NEUROLOGIC COMPLICATIONS OF CARDIAC TRANSPLANTATION
1988; 6 (2): 349-365
The neurologic evaluation of an individual cardiac transplant recipient often does not lead to a succinct bedside diagnosis. There are few consistent clinical observations. The onset of seizures in the early postoperative period is associated with embolic cerebral infarction. Seizures occur most commonly, however, as a neurotoxic manifestation of cyclosporine. The onset of an acute delirium or psychosis in the first week after cardiac transplantation usually has multiple causative factors and is reversible. A postoperative brachial plexopathy or mononeuropathy can be identified with a neurologic examination, confirmed by appropriate electrophysiologic testing and is usually reversible. The onset of periorbital inflammation, ophthalmoplegia, and nasal turbinate or sinus invasion and necrosis is consistent with phycomycosis. Most patients, however, present with nonspecific findings of impaired mentation with or without focal neurologic signs. These patients require a fairly systematic search for potentially treatable neurologic complications (see Table 3). In a medically stable patient an aggressive diagnostic approach, at times including stereotaxic brain aspirate or biopsy, is indicated. In the severely ill patient with multiple organ failure, empirical therapy for the most probable treatable disorder is justified.
View details for Web of Science ID A1988N996200008
View details for PubMedID 3047545
STIMULUS CONDITIONS THAT ENHANCE ANTICIPATORY SLOW EYE-MOVEMENTS
1988; 28 (10): 1157-1165
Anticipatory slow eye movements are predictive responses that occur prior to both ramp and step target motions. These low velocity eye movements are enhanced and can be studied in isolation by transient target disappearance before ramp motion onset. Slow eye velocities also decrease prior to the termination of target motion. In experiments using a bistable apparent motion stimulus, it was found that perceived motion is a stimulus for anticipatory slow eye movements. This relationship between motion perception and anticipatory slow eye movements can explain previously noted differences between these predictive movements and the predictive component of smooth pursuit.
View details for Web of Science ID A1988Q500100012
View details for PubMedID 3257018
SMOOTH PURSUIT TRAINING AND DISRUPTION - DIRECTIONAL DIFFERENCES AND NYSTAGMUS
1987; 7 (4): 185-194
View details for Web of Science ID A1987K140400002
- Smooth pursuit training and disruption: directional differences and nystagmus Neuro-Ophthalmology 1987; 7: 185-194
THE SEARCH FOR A PHYSIOLOGICAL MARKER OF MACHADO-JOSEPH DISEASE
1987; 37 (1): 112-116
Machado-Joseph disease is a dominantly inherited, multisystem, degenerative disorder that lacks a proven genetic marker. Peripheral nerve conduction-refractory period, sensory evoked potentials, and quantified oculomotor recordings were studied in nine patients affected with this disease to look for a potential physiologic marker. Only the oculomotor measurements of saccade and smooth pursuit gain were consistently abnormal in all patients. Identical eye movement recordings in 12 asymptomatic individuals at risk for Machado-Joseph disease revealed findings typical of affected patients in only 1 individual. Quantified oculomotor studies may contribute to the early confirmation of the disease, primarily in individuals at risk with minor or equivocal neurologic signs.
View details for Web of Science ID A1987F561100019
View details for PubMedID 3467220
SACCADE RESPONSES TO DOPAMINE IN HUMAN MPTP-INDUCED PARKINSONISM
ANNALS OF NEUROLOGY
1986; 20 (4): 456-463
Depletion of dopamine content in the substantia nigra resulting from 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) toxicity produces parkinsonism. Management of 3 patients with MPTP-induced parkinsonism required drug holidays during which there was a state of dopamine depletion followed by dopamine replacement. We used this opportunity to study the effect of the selective loss of pars compacta dopaminergic cells on vertical and horizontal saccade (fast) eye movements. During the drug holidays, visually guided saccades were hypometric and had long latencies but retained a normal saccade velocity-amplitude relationship. Dopamine agonists or precursors improved the accuracy and reaction times of saccades in all directions, but not their velocity. Two of the three patients also had intermittent blepharospasm during dopamine depletion. During the episodes of blepharospasm, saccade responses became slow eye movements. MPTP causes a dopaminergic-responsive disorder of saccade initiation that is similar to idiopathic parkinsonism. The inhibition of voluntary eyelid opening during MPTP-induced blepharospasm further increases this impairment of fast eye movements and altered saccade velocity, presumably via the pars reticulata of the substantia nigra.
View details for Web of Science ID A1986E435600003
View details for PubMedID 3491578
REGIONAL COOLING OF HUMAN NERVE AND SLOWED NA+ INACTIVATION
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1986; 63 (4): 371-375
Regional cooling of human sensory nerves increases the amplitude and surface area of an evoked sensory compound action potential (SCAP). It has been proposed that these changes are due to cold-induced slowing of Na+ inactivation. Na+ inactivation is also the main voltage-dependent event that underlies the refractory period in myelinated nerve. Therefore, if slowed Na+ inactivation causes the increased SCAP amplitude and area seen in focal cooling, a parallel temperature-dependent change should also occur in the SCAP refractory period. We compared the duration and magnitude of the relative refractory period to the total surface of a median nerve SCAP at 5 intervals of increasing temperature, from 24 degrees C to 36 degrees C. In 5 control subjects, the SCAP surface area and the relative refractory period increased 4-5-fold in parallel and revealed a non-linear relation to temperature change. Prolongation of the duration of individual nerve fiber potentials from slowed Na+ inactivation is proposed as one explanation of these temperature-related changes.
View details for Web of Science ID A1986A719900008
View details for PubMedID 2419095
CLINICAL DETECTION OF ACUTE VESTIBULOCEREBELLAR DISORDERS
WESTERN JOURNAL OF MEDICINE
1984; 140 (6): 910-913
The acute onset of vertigo, nystagmus and postural instability, without brain-stem signs, is commonly attributed to a disorder of the labyrinth, the vestibular, sensory end organ. Identical symptoms can occur, however, with discrete infarctions or hemorrhages involving the central vestibulocerebellum. Whereas acute labyrinthine disorders are usually benign and self-limited, vascular injuries of the cerebellum may produce swelling, compression of the brain stem and acute hydrocephalus one to four days after the onset of symptoms. Therefore it is important to accurately distinguish between labyrinthine and vestibulocerebellar disorders with the neurologic examination. Acute labyrinthine disease causes unidirectional nystagmus with past-pointing and falling in the opposite direction of the nystagmus, environmental vertigo in the same direction and suppression of the nystagmus with visual fixation. Disorders of the vestibulocerebellum do not produce this consistent pattern of findings.
View details for Web of Science ID A1984SW69400005
View details for PubMedID 6741122
VERTICAL SACCADES IN HUNTINGTONS-DISEASE AND NON-DEGENERATIVE CHOREOATHETOID DISORDERS
1984; 4 (4): 207-217
View details for Web of Science ID A1984TZ41300003
CONVERGENCE-INITIATED VOLUNTARY FLUTTER - A NORMAL INTRINSIC CAPABILITY IN MAN
1984; 294 (2): 299-304
The proposal that there is an inherent capability in humans to produce bursts of fluttering saccades was tested by comparing Purkinje image eye movement recordings in subjects with voluntary nystagmus and control subjects. Voluntary nystagmus is composed of recurrent saccades without an intersaccade interval and has been proposed to be an inherited event. No difference in saccade peak velocity-amplitude curves or microsaccades during visual fixation was found between the two groups. With training control subjects learned to produce runs of saccadic flutter identical to voluntary nystagmus. This learned flutter was composed of recurrent complete saccades rather than saccades interrupted in midflight. Voluntary flutter is thus not a genetic trait but a learned event that is usually undeveloped in man. These observations can be explained by the Robinson model of saccade generation and indicate that similar models must have an inherent ability to produce saccadic flutter.
View details for Web of Science ID A1984SH38800011
View details for PubMedID 6704727
1983; 33 (1): 101-103
Dementia was the presenting symptom in a patient with increased serum viscosity secondary to multiple myeloma. Plasmapheresis led to complete resolution of the neurologic syndrome. Serum hyperviscosity should be added to the growing list of reversible causes of dementia. When hyperviscosity-associated dementia is suspected, both serum and whole blood viscosity determinations are indicated.
View details for Web of Science ID A1983QB71200020
View details for PubMedID 6681548
CEREBELLAR CONTROL OF FIXATION EYE-MOVEMENTS
1982; 32 (1): 31-36
Human subjects normally have miniature eye movements during tasks that require steady visual fixation. These eye movements were compared in 12 control subjects and 4 patients with degenerative cerebellar disorders. Slow drifts, small fixation saccades, square waves, saccadic oscillations, flutter, and vertical nystagmus occurred in both control subjects and patients. In the patients, however, fixation eye movements were enlarged and square waves and saccadic oscillations were more frequent. It appears that some forms of pathologic fixation instability are due to defective cerebellar control of fixation eye movements, and that precise measurements of these eye movements may quantitate disorders of cerebellar function.
View details for Web of Science ID A1982MY35400005
View details for PubMedID 7198730
- AMITRIPTYLINE - ANOTHER CAUSE OF INTER-NUCLEAR OPHTHALMOPLEGIA WITH COMA ANNALS OF NEUROLOGY 1982; 12 (1): 62-62
MODERN NEUROSYPHILIS - A PARTIALLY TREATED CHRONIC MENINGITIS
WESTERN JOURNAL OF MEDICINE
1981; 135 (3): 191-200
Approximately 5,000 new cases of neurosyphilis may occur in the United States each year. General paresis and tabes dorsalis, however, have become relatively rare since the introduction of penicillin. Seizures, neuro-ophthalmologic symptoms, stroke and acute meningoencephalitis are currently the most common manifestations of neurosyphilis. In more than a third of patients with neurosyphilis, nontreponemal tests for syphilis (such as VDRL) are negative and should not be used to exclude the diagnosis. Specific treponemal tests are more sensitive and more specific. Examination of the cerebrospinal fluid may show no abnormalities in neurosyphilis and is not an infallible guide to the activity of the infection. Penicillin is the only proven antibiotic treatment of neurosyphilis. However, low-dose regimens do not produce spirocheticidal concentrations in the brain, and high-dose penicillin therapy is recommended to insure eradication of the spirochetes. Doxycycline, a tetracycline derivation that achieves relatively high concentration in the brain, may also be effective.
View details for Web of Science ID A1981MG22400004
View details for PubMedID 7340118
PENICILLIN-INDUCED AND BARIUM-INDUCED EPILEPTIFORM BURSTING IN HIPPOCAMPAL-NEURONS - ACTIONS ON CA++ AND K+ POTENTIALS
ANNALS OF NEUROLOGY
1981; 10 (1): 11-17
Both barium (Ba++) and penicillin produce spontaneous epileptiform burst generation in hippocampal neurons in vitro. Recent investigations suggest that Ba++ acts by both adding to a calcium (Ca++)-mediated depolarization and reducing potassium (K+) conductance. In contrast, it has been proposed that penicillin produces burst generation by attenuating inhibitory postsynaptic potentials. However, some evidence suggests that penicillin may also directly alter intrinsic membrane properties. We therefore compared the actions of penicillin and Ba++ on three intrinsic Ca++- or K+-mediated membrane events, namely, CA++ spikes, Ca++-dependent anomalous rectification, and K+-dependent afterhyperpolarization. Ba++ augmented the Ca++ potentials and attenuated the K+-dependent afterhyperpolarization; penicillin had no demonstrable effect on these events. Ba++ produced rhythmical burst firing and oscillations of the membrane potentials, while penicillin caused sporadic burst generation followed by a longlasting afterhyperpolarization. Synchronized, orthodromically evoked burst firing occurred after exposure to penicillin but not to Ba++. Ba++ and penicillin are prototypes of agents which induce epileptogenesis in mammalian cortical neurons by two different but probably interrelated mechanisms. Ba++ causes burst generation by disrupting a delicate balance between depolarizing Ca++ potentials and repolarizing, hyperpolarizing K+ potentials. Penicillin does not affect Ca++- or K+-mediated membrane events; other data suggest that it produces burst generation in hippocampal pyramidal neurons by attenuating gamma-aminobutyric acid-mediated synaptic inhibition, which in turn ordinarily limits intrinsic bursting.
View details for Web of Science ID A1981LY67500002
View details for PubMedID 7271228
CALCIUM-ACTIVATED HYPERPOLARIZATION FOLLOWS REPETITIVE FIRING IN HIPPOCAMPAL-NEURONS
JOURNAL OF NEUROPHYSIOLOGY
1980; 43 (2): 409-419
1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.
View details for Web of Science ID A1980JF63200011
View details for PubMedID 6247461
ANOMALOUS INWARD RECTIFICATION IN HIPPOCAMPAL-NEURONS
JOURNAL OF NEUROPHYSIOLOGY
1979; 42 (3): 889-895
1. Anomalous rectification occurred in 54 of 56 hippocampal CA1 neurons studied in vitro. This phenomenon is characterized by a progressive increase in input resistance with membrane depolarization. An average increase in membrane resistance of 45% occurred over a 15-mV region of membrane potential immediately subthreshold to cellular firing. 2. Both Mn2+, a Ca+ antagonist, and tetrodotoxin (TTX), a neurotoxin that blocks regenerative Na+ currents, eliminated anomalous rectification. Ba2+, which can both contribute to intracellular cation influx as well as reduce K+ conductance, increased the magnitude of anomalous rectification. The observations are indirect evidence indicating that a Ca2+-Na+ current may produce the inward-going rectification. 3. Enhancement of anomalous rectification by Ba2+ was associated with the onset of membrane oscillations and spontaneous bursts of repetitive discharges. The magnitude of anomalous rectification may be one factor that predisposes some cortical neurons to bursting behavior.
View details for Web of Science ID A1979GU49800018
View details for PubMedID 430121
Penicillin- and barium-induced epileptiform bursting in hippocampal neurons: actions on calcium- and potassium-dependent potentials.
Transactions of the American Neurological Association
1978; 103: 56-58
View details for PubMedID 757089
NEUROLOGICAL COMPLICATIONS OF CARDIAC TRANSPLANTATION
1976; 99 (DEC): 673-694
Review of the neurological complications encountered in 83 patients who received cardiac homografts over a seven-year period leads to the following conclusions: (1) Neurological disorders are common in transplant recipients, occurring in over 50 per cent of patients. (2) Infection was the single most frequent cause of the neurological dysfunction, being responsible for one-third of all CNS complications. (3) The infective organisms were typically those considered to be usually of low pathogenicity: fungi, viruses, protozoa and an uncommon bacterial strain. (4) Other clinical neurological syndromes were related to vascular lesions, often apparently from cerebral ischaemia or infarction occurring during the surgical procedure, metabolic encephalopathies, cerebral microglioma, acute psychotic episodes and back pain from vertebral compression fractures. (5) The infectious complications and probably the development of neoplasms de novo, are related to immunosuppressive therapy which impairs virtually all host defence mechanisms and alters the nature of the host's response to infective agents or other foreign antigens. (6) Because neurological symptoms and signs were usually those of behavioural changes or deterioration in intellectual performance, the neurological examination was often of little value in diagnosing the nature or even the anatomical site of the neuropathological process. (7) The possibility of an infectious origin of the neurological manifestations must be aggressively pursued even in the absence of fever and a significantly abnormal spinal fluid examination. The diagnostic error made most frequently was to ascribe neurological symptoms erroneously to metabolic disturbances or to "intensive care unit psychosis" when they were in fact due to unrecognized CNS infection. (8) Maintenance of mean cardiopulmonary bypass pressures above 70 mmHg, particularly in patients with known arteriosclerosis, may reduce operative morbidity. (9) Though increased diagnostic accuracy is possible with routine use of a variety of radiological and laboratory techniques, two further requirements probably must be met before a significant reduction in the frequency of neurological complications will occur: the advent of greater immunospecificity in suppressing rejection of the grafted organ while preserving defences against infection; and a more effective armamentarium of antiviral and antifungal drugs.
View details for Web of Science ID A1976DB36300004
ARCHIVES OF NEUROLOGY
1976; 33 (2): 141-142
Two patients with disulfiram-(Antabuse-)induced encephalopathy exhibited paranoid ideas, disorientation, impaired memory, ataxia, dysarthria, snout and grasp reflexes, and abnormal electroencephalograms. The first patient developed symptoms on two occasions, each time after disulfiram administration. The second patient experienced a generalized seizure followed by fulminant psychosis three weeks after starting disulfiram therapy. Spinal fluid examination in the latter patient revealed a low homovanillic acid (HVA) level. Since disulfiram inhibits dopamine oxidation, disulfiram-induced encephalopathy may be related to excess dopaminergic activity in the central nervous system.
View details for Web of Science ID A1976BD60300012
View details for PubMedID 1252149
- EXTRACELLULAR POTASSIUM CONCENTRATION CHANGES DURING PROPAGATED SEIZURES IN NEOCORTEX EXPERIMENTAL NEUROLOGY 1973; 38 (1): 20-26